Extracellular Fluid Research Articles

Short-Lived Active Prorenin: Precursor of So-Called Native Prorenin.

The enzymatic activity of the aspartic protease, renin, is critical for its function in blood pressure regulation and sodium homeostasis. Incubation of so-called native prorenin at low pH leads to its activation. After binding to transition-state mimicking renin inhibitors at neutral pH, prorenin attains the active conformation, as indicated by immunosorbent assay using monoclonal antibodies specific for epitopes of the prosegment or the renin body. A comparison of immunosorbent assay with enzyme-kinetic assay revealed the intermediary steps of prorenin auto-activation/inactivation. The kinetically identified intermediary steps of activation/inactivation correspond with the published crystal structures of free renin, free prorenin, and renin in complex with inhibitors. Both renin and activated prorenin exist in 2 forms, α and β. The α form is active, and the α/β quantity ratio is 2.5. The kidney produces renin and prorenin, while the ovarium, placenta, and eye produce inactive prorenin. The production of renin by these organs has never been demonstrated. We propose that the so-called native prorenin in extracellular fluid, including the circulation, is derived, at least partly, from short-lived active prorenin. Its potential paracrine function is discussed.

Acute response to resistance exercise and later development of arm lymphedema in breast cancer survivors: An exploratory follow-up of a randomized cross-over trial

BackgroundIn breast cancer survivors at risk for lymphedema, variation in lymphatic function and arm volume has been observed related to a bout of exercise, with potential for prediction of breast cancer-related arm lymphedema (BCRaL). This novel, exploratory study examined the acute lymphatic response to resistance exercise and later development of BCRaL in women at high risk for BCRaL. MethodsOne year after participation in a cross-over trial evaluating the acute lymphatic response to upper-extremity resistance exercise (low-and heavy-load), participants were assessed for BCRaL (n ​= ​16). The response to exercise was assessed before and after (post, 24- and 72-hrs) each exercise bout as extracellular fluid (L-Dex; bioimpedance spectroscopy (BIS)), interarm volume % difference (IVD; Dual-energy x-ray absorptiometry (DXA)) and symptoms (Numeric rating scale, 0–10 (NRS)). BCRaL at follow-up was defined as presence of one objective indicator (L-Dex >10, change ≥+6.5, IVD >5%) plus one objective or subjective indicator (interarm symptom ≥1 or visual inspection). Descriptive statistics were used to compare the acute response between participants with and without BCRaL at follow-up. ResultsNo trends indicating a similar acute response to exercise was observed in participants who later developed BCRaL (n ​= ​5). There were no observable differences in acute lymphatic response between participants that developed BCRaL and those who did not, both at an individual and group level. ConclusionsFindings from this exploratory study showed no evidence to suggest that the acute response to resistance exercise can predict BCRaL development.

Cardiovascular Magnetic Resonance Radiomics to Identify Components of the Extracellular Matrix in Dilated Cardiomyopathy.

Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy. We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T1, extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation. Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P<0.001). There was a similar trend in the addition of native T1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P<0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P=0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T1, ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T1, ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively). Radiomic features extracted from native T1, ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy.

Laterality of CT-measured hepatic extracellular volume fraction in patients with chronic thromboembolic pulmonary hypertension.

This study examines the hepatic extracellular volume fraction (ECV) disparity between the left and right lobes (ECV_left and ECV_right) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its association with right heart catheterization (RHC) metrics, and with intolerance to increased pulmonary hypertension (PH)-targeted medication dosages. We retrospectively analyzed 72 CTEPH-diagnosed patients who underwent equilibrium-phase abdominal dual-energy CT (DECT) and RHC. Hepatic ECVs, derived from DECT's iodine maps using circular regions of interest in the liver and aorta, were correlated with RHC parameters via Spearman's rank correlation and lobe differences through the Wilcoxon signed-rank test. Logistic regression assessed cases with ECV_left exceeding ECV_right by > 0.05, while receiver operating characteristic curve analysis gauged ECVs' predictive power for medication intolerance. Of the 72 patients (57 females; median age 69), ECV_total (0.24, IQR 0.20-0.27) moderately correlated with RHC parameters (rs = 0.28, -0.24, 0.3 for mean pulmonary arterial pressure, cardiac index [CI], and pulmonary vascular resistance index, respectively). ECV_left significantly surpassed ECV_right (0.25 vs. 0.22, p < 0.001), with a greater ECV_left by > 0.05 indicating notably lower CI (p < 0.001). In 27 patients on PH medication, ECV_left effectively predicted medication intolerance (AUC = 0.84). In CTEPH patients, hepatic ECV correlated with RHC metrics, where elevated left lobe ECV suggested reduced CI and potential medication intolerance.

Association of cardiovascular fibrosis, remodeling, and dysfunction with frailty, pre-frailty, and functional performance: the Multi-Ethnic Study of Atherosclerosis (MESA).

Cardiovascular disease is associated with higher incidence of frailty. However, the nature of the mechanisms underlying this association remain unclear. The purpose of this study is to identify cardiovascular phenotypes most associated with physical frailty and functional performance in the Multi-Ethnic Study of Atherosclerosis (MESA). As part of the MESA study, 3045 participants underwent cardiovascular magnetic resonance and computed tomography between 2010-2012. Of these, 1743 completed a Six-Minute Walk test (6MWT) and questionnaires (follow-up Exam: 2016-2018) which were used to generate a binary combined frail/prefrail vs. robust score according to a modified FRAIL Scale (self-report questionnaire). Multivariable logistic (binary frail outcome) or linear (6MWT) regression assessed the association between frailty and cardiovascular structure and function, aortic stiffness, coronary artery calcium, and myocardial fibrosis (ECV, extracellular volume fraction). Participants were 66±8yrs, 52% female at the time of imaging, and 29.4% were classified as frail or pre-frail. Older age and female gender were associated with greater odds of being in the frail/prefrail group. Concentric left ventricular remodeling (OR 1.89,p=0.008; Coef. -52.9,p<0.001), increased ECV (OR 1.10,p=0.002; Coef. -4.0,p=0.001), and worsening left atrial strain rate at early diastole (OR 1.56,p=<0.001; Coef. -22.75,p=0.027) were found to be associated with a greater likelihood of being in a frail state and lower 6MWT distance (m) . All associations with 6MWT performance were attenuated with adjustments for risk factors while ECV and LA strain rate remained independently associated with frailty. These findings suggest a significant overlap in pathways associated with subclinical cardiac dysfunction, cardiovascular fibrosis and physical frailty.

Rudimentary Overview: Dehydration (Loss of Body Water) Recognition and Management

Dehydration occurs when the body loses more water than it gains, mostly from the intracellular volume (ICV). Low-intake dehydration is the consequence of consuming insufficient amounts of pure water, which increases the osmolality of both compartments and resulting in the loss of intracellular and extracellular fluid. Clinically, volume depletion affects the interstitial compartment and is brought on by excessive losses of fluid and salt, especially sodium and occasionally other elements. The main cause of the fluid loss is a decrease in extracellular volume (ECV); the serum osmolality will either be low or normal. From a physiological standpoint, it makes sense that many clinicians refer to any loss of total body water as dehydration in their routine clinical practice. Most people who have mild to moderate dehydration as a result of vomiting, diarrhoea, or fever can recover by drinking more liquids, such water. Full-strength fruit juice and soft drinks might make diarrhoea worse. If you work outside or exercise in hot or muggy weather, your best bet is cool water. The best way to treat dehydration is to replenish the body with enough of fluids, such as water, diluted squash, or diluted fruit juice. A salty snack can help you replace lost salt, while a sweet drink can help you replace lost sugar. We go over the causes, prevalence, accessible therapies, and present state of dehydration in this review study.

Nomogram based on dual-energy CT-derived extracellular volume fraction for the prediction of microsatellite instability status in gastric cancer

PurposeTo develop and validate a nomogram based on extracellular volume (ECV) fraction derived from dual-energy CT (DECT) for preoperatively predicting microsatellite instability (MSI) status in gastric cancer (GC).Materials and methodsA total of 123 patients with GCs who underwent contrast-enhanced abdominal DECT scans were retrospectively enrolled. Patients were divided into MSI (n=41) and microsatellite stability (MSS, n=82) groups according to postoperative immunohistochemistry staining, then randomly assigned to the training (n=86) and validation cohorts (n=37). We extracted clinicopathological characteristics, CT imaging features, iodine concentrations (ICs), and normalized IC values against the aorta (nICs) in three enhanced phases. The ECV fraction derived from the iodine density map at the equilibrium phase was calculated. Univariate and multivariable logistic regression analyses were used to identify independent risk predictors for MSI status. Then, a nomogram was established, and its performance was evaluated by ROC analysis and Delong test. Its calibration performance and clinical utility were assessed by calibration curve and decision curve analysis, respectively.ResultsThe ECV fraction, tumor location, and Borrmann type were independent predictors of MSI status (all P &amp;lt; 0.05) and were used to establish the nomogram. The nomogram yielded higher AUCs of 0.826 (0.729–0.899) and 0.833 (0.675–0.935) in training and validation cohorts than single variables (P&amp;lt;0.05), with good calibration and clinical utility.ConclusionsThe nomogram based on DECT-derived ECV fraction has the potential as a noninvasive biomarker to predict MSI status in GC patients.

Volume-weighted unipolar voltage identifies diffuse fibrosis in patients with non-ischemic cardiomyopathy

Abstract Background Late-gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMR) is currently used to identify non-ischemic scar. However, the distribution of non-ischemic fibrosis related to ventricular arrhythmia (VA) may vary between patients and cannot be accurately delineated by LGE-CMR. Myocardial extracellular volume fraction (ECV) is a promising tool to estimate the amount of diffuse fibrosis in non-ischemic cardiomyopathies (NICM). Novel intra-cardiac mapping derived tools, such as volume-weighted unipolar voltage (vwUV), may allow intraprocedural quantification of diffuse fibrosis. Purpose To evaluate the performance of vwUV to determine the segmental amount of non-ischemic fibrosis defined by whole-heart T1 mapping. Methods Consecutive patients with a left dominant NICM referred for ablation of VA, who underwent 3D LGE-CMR, whole-heart pre- and post-contrast T1 mapping and high density electroanatomical voltage mapping (EAVM) were included. CMR images were segmented and merged with the 3D EAVM data. The 16-segment AHA model was applied and vwUV and ECVs were determined per segment. Results Twenty-one patients (age 54 years [49-60], 18 males [87%], LVEF 47% [37-57%], LGE 7.7% (2.8-18.2%) of LV myocardium) were included and 305 segments analysed. The median ECV per patient was 30.3% (28.8-35.2%). The median segmental vwUV was 1.8mV (1.2-2.3mV). The basal septal and basal inferolateral segments tended to have higher ECV. However there was important variation between patients (figure 1). Of note, the segmental vwUV correlated well with segmental ECV (r = -0.53, p &amp;lt; 0.001) (figure 2). Conclusions For the first time, a segmental comparison has been performed between ECV and vwUV. There are important segmental variations of ECV between patients with a NICM referred for VA ablation. The novel intra-cardiac mapping-derived tool of vwUV can localize non-ischemic fibrosis and may facilitate substrate based ablation approaches in this challenging patient population.Figure 1.Segmental ECV valuesFigure 2.Segmental ECV and vwUV

#2464 Association of vascular access flow and volume status on fistula arm by bio-impedance analysis

Abstract Background and Aims Multi-frequency bio-impedance is a tool of body composition measure and can monitor changes in extracellular volume during dialysis. Arterio-venous fistulae (AVF) could potentially affect fluid retention in the arm. We investigated whether multi-frequency bio-impedance could defect AVF stenosis or association of AVF with fluid retention in the AVF arm. Method We measured the extracellular water (ECF) and total body water (TBW) in AVF arm following hemodialysis by multi-frequency bio-impedance (Inbody S10®) using an eight-electrode contact technique. We measured AVF or AVG flow by transonic ultrasonography using an ultrasound dilution technology (HD 03®) in hemodialysis. Results Total 82 patients (male 38 patients : female 44 patients) were enrolled. The causes of ESRD were DM : non-DM = 38 : 44. The mean age of patients was 54.89 ± 13.21 years. The ECW/TBW ration of fistula arm was a significantly higher than the ECW/TBW ration of non-fistula arm (0.389 ± 0.010 vs. 0.382 ± 0.001; p&amp;lt;0.05). The ECW/TBW ration of fistula arm was a significantly negative correlation with access flow level (mL/min) on fistula (p&amp;lt;0.05). The 5kHz reactance of fistula arm was a significantly positive correlation with access flow level (mL/min) on fistula (p&amp;lt;0.05). The 5kHz Phase Angle of fistula arm was a significantly positive correlation with access flow level (mL/min) on fistula (p&amp;lt;0.05). Conclusion Absolute and also relative extracellular fluid volumes are increased in the fistula arm of hemodialysis. We thought that extracellular fluid volumes in the fistula arm were associated with access flow level (mL/min) and/or relative fistula stenosis. We suggest that multi-frequency bio-impedance can be a useful assistant tool of vascular access flow measure.

#205 Features of chronic kidney disease in patients with obesity and arterial hypertension

Abstract Background and Aims to assess the indicators of composite body composition in patients with obesity and chronic kidney disease with arterial hypertension. Method 59 patients with obesity and arterial hypertension were examined. When selecting patients, inclusion criteria were taken into account: men and women aged 25 to 55 years, obesity (BMI more than 30 kg/m²; waist circumference (WC) more than 80 cm in women and more than 94 cm in men), presence of hypertension I– Stage II, grade 1–2, absence of renal pathology (history of kidney disease, structural changes in the parenchyma and vessels of the kidneys during ultrasound examination, changes in urinary sediment and urine density, proteinuria, decreased GFR less than 60 ml/min/1.73 m² ), signed informed consent. Metabolically complicated obesity was defined as the presence of abdominal obesity, a BMI of more than 30 kg/m2 in combination with hypertension and ≥ 2 cardiometabolic abnormalities. A metabolically healthy obesity phenotype was considered to be the presence of obesity without hypertension, dyslipidemia, or hyperglycemia. The results obtained during the study were compared with the indicators of a control group formed from 30 practically healthy individuals aged 25–55 years without obesity or overweight. Differences in age, gender, duration of hypertension and obesity were not established. Metabolic activity of adipose tissue was assessed by the level of leptin, soluble leptin receptors (sLR), adiponectin, resistin, free leptin index (FLI), leptin/adiponectin index (L/A). Renal function: GFR (CKD EPI and Hoek), serum and urine cystatin C, albuminuria. The composite composition of the body was studied using bioimpedance analysis using an ABC-01 Medass analyzer of body composition and balance of water sectors of the body. Results In a comparative analysis of the parameters of the composite body composition in the obese groups, the highest values ​​of fat mass (42.8 ± 6.8 and 35 ± 4.2 kg) and total fluid (40.2 ± 5.0 and 36.0 ± 2.8 kg) with a reduced proportion of 17 active cell mass (ACM) (53.0 ± 3.2 and 56.1 ± 3.4%) were detected in patients with complicated obesity (p &amp;lt; 0.05). Regardless of the obesity phenotype, correlations were established: between the level of diastolic blood pressure (DBP) and the volume of total (r1 = 0.42; r2 = 0.52) and extracellular fluid (r1 = 0.50; r2 = 0.60); level of DBP and urinary excretion of cystatin C (r1 = 0.51; r2 = 0.61) (p &amp;lt; 0.01). A decrease in the proportion of ACM in obese groups was associated with an increase in resistin levels (r1 = −0.56; r2 = −0.31). In obese groups, regardless of phenotype, fat mass was associated with leptin levels (r1 = 0.52; r2 = 0.42) and free leptin index (FLI) (r1 = 0.75; r2 = 0.46 ) (p &amp;lt; 0.05). In group 1, a positive correlation was additionally established for the volume of fat mass with systolic blood pressure (SBP) (r1 = 0.70) and DBP (r1 = 0.65), with the level of uric acid (r1 = 0.57), cholesterol LDL (r1 = 0.52), cystatin C in urine (r1 = 0.75) and insulin resistance index (HOMA-IR) (r1 = 0.65) (p &amp;lt; 0.01). Conclusion Body mass index does not determine the obesity phenotype. In patients with complicated obesity, the proportion of fat mass is higher than in metabolically healthy obesity and is associated with increased levels of glucose and uric acid. All obese patients are characterized by an increase in the percentage of total and extracellular fluid, associated with the level of blood pressure and urinary excretion of markers of tubular dysfunction.

Endothelin-1, Extracellular Volume Overload, and Hemodynamics in Hemodialysis Patients.

Extracellular volume (ECV) overload and endothelial cell dysfunction (ECD) are independent risk factors for mortality in hemodialysis patients. Endothelin-1 (ET-1), an endothelium-derived vasoconstrictive peptide, is associated with poor outcomes in hemodialysis patients and heart failure patients without kidney disease. We hypothesized there would be associations between ET-1 and ECV overload assessed with bioimpedance spectroscopy (BIS) in hypertensive hemodialysis patients. We obtained pre-HD plasma ET-1, ECV/weight (using multi-frequency BIS), pre-HD hemodynamic measurements, and ambulatory blood pressure (BP) in a cohort of HD patients. Following appropriate transformations, we conducted correlation and linear regression analyses to identify associations between ET-1 and ECV overload. We further explored associations between ET-1 and total peripheral resistance index (TPRI), cardiac index (CI), and ambulatory BP. Among 66 patients, median ET-1 was 1.93 (1.49-2.56) pg/mL. Median pre-HD ECV/weight, median TPRI, mean CI, and mean systolic ambulatory BP were 0.25 (0.22-0.30) L/kg, 3161 (2711-3642) dynes*sec/cm-5/m2, 2.92 (0.6) L/min/m2, and 143 (14) mmHg, respectively. After reciprocal transformation, ET-1 correlated with reciprocal-transformed ECV/weight (r=0.3, p=.01), log-transformed TPRI (r=-0.3, p=.006), CI (r=0.3, p=.009) and ambulatory BP (r=-0.3, p=.02). Controlling for demographic variables, these associations persisted in linear regression analysis (β=0.15, p=.002; β=-0.8, p=.002; β=0.2, p=.002; β=-19, p=.03). In hypertensive HD patients, ECV overload is associated with ET-1. ET-1 is associated with higher TPRI and lower CI before dialysis and higher ambulatory BP. Further research is necessary to determine if ECV reduction lowers ET-1 or if pharmacologic ET-1 antagonism can improve outcomes in HD patients with refractory ECV overload.

#2118 Monitoring hemodynamics in dialysis: on the feasibility of semi-continuous and multifrequency thoracic bioimpedance measurements by a wearable device

Abstract Background and Aims Hemodialysis patients face a high hemodynamic variability in blood pressure and fluid status, which contributes to their cardiovascular mortality. Currently, intradialytic hemodynamic monitoring has to rely on cuff-based blood pressure measurements. During the interdialytic interval, no monitoring system is applied. An interesting alternative to monitor hemodynamics continuously can be found in the bioimpedance technique, and more specifically in bioimpedance measurements of the thoracic segment. Repeated single-point measurements of thoracic bioimpedance at single (low)-frequency are strongly related to fluid changes during hemodialysis. Extension to semi-continuous measurements may provide longitudinal details in the time pattern of the bioimpedance signal, and multifrequency measurements may add in-depth information on the distribution between intra- and extracellular fluid. This study aims to investigate the feasibility of semi-continuous multifrequency thoracic bioimpedance measurements by a wearable device in hemodialysis patients. Method Thoracic bioimpedance was recorded semi-continuously (i.e. every ten minutes) at nine frequencies (8–160 kHz) in 68 patients during two consecutive hemodialysis sessions, complemented by an interdialytic single-point measurement at home. The wearable bioimpedance device was provided by imec, The Netherlands (Fig. 1). A linear mixed model was built to integrate all measurements at frequencies 8 and 160 kHz, incorporating the different dialysis sessions up until 240 minutes after the start of dialysis as well as the home measurement that was performed. Results On average, the thoracic resistance signals increased during the first hemodialysis session, decreased during the interdialytic interval, and increased again during the second hemodialysis session, at all frequencies. The average intradialytic increase was larger at 8 kHz (∆ 32.6 Ω during session 1 and ∆ 10 Ω during session 2) compared to 160 kHz (∆ 29.5 Ω during session 1 and ∆ 5.1 Ω during session 2). By measuring semi-continuously and at multiple frequencies, a different time pattern became clear within and between frequencies. The resistance at 8 kHz followed a linear time pattern, whereas the evolution of the resistance at 160 kHz showed a significant quadratic trend in the first dialysis session (p &amp;lt; 0.0001). During the first interdialytic interval (from the end of the first dialysis session towards the home measurement), the decrease in resistance was more distinct at 8 kHz (∆ −2.27 Ω) compared to a small increase of 0.84 Ω in 160 kHz. This finding reveals a certain inertia in the higher frequencies, mirroring the changes in intracellular volume. Finally, the statistical model could create individual predicting profiles over time, including as well the intradialytic as the interdialytic interval (Fig. 2). Conclusion In this study, we showed that it is feasible to perform semi-continuous and multifrequency bioimpedance measurements by a wearable device during hemodialysis. Semi-continuous and multifrequency measurements provided a broader, and respectively profounder knowledge on the trend of the bioimpedance signal during fluid changes compared to single-point and single-frequency measurements. Measuring thoracic bioimpedance semi-continuously and with a multifrequency current is a major step forward in the understanding of fluid dynamics in hemodialysis patients, by which the road is paved towards remote fluid monitoring and the prevention of hemodynamic instabilities.

#1024 Lung ultrasound in 28 versus 8 places and volume status in chronic hemodialysis patients

Abstract Background and Aims Overhydration is considered a significant risk factor for cardiovascular and all-cause mortality in end-stage kidney disease patients. Measurement of total and extracellular water with bioelectrical impedance analysis (BIA), inferior vena cava diameter (IVCd) measurement, and circulating pro-B-type natriuretic peptide (proBNP) levels have previously been tested as possible indicators of volume status in hemodialysis (HD) patients, with BIA showing the most potential. Recently, it has been shown that lung ultrasound (LUS)-guided volume depletion is an effective strategy for relieving lung congestion in chronic HD patients. The aim of our study was to determine whether performing LUS on only 8 places was comparable to the regular 28 places. Method LUS was performed on 29 randomly selected patients before their regular HD procedure in 28 regular places and correlated with 8 places (4 on each side). In addition, BIA with a body composition monitor (BCM) was performed, IVCd was measured using ultrasound and serum NT-proBNP value was determined. Statistical analysis was performed using a commercially available SPSS® for Windows® (version 29.0; Chicago, IL, USA). Spearman's non-parametric test was used to determine a correlation between variables. P-values less than 0.05 were considered statistically significant. Results We included 29 chronic HD patients, 15 male (51.7 %), with a mean age of 66.3 ± 12.5 years and a median dialysis vintage of 53.0 (95% CI (40.9, 100.6)) months. Most patients (96.6 %) had a functional arteriovenous fistula, whereas only one patient (3.4 %) was dialysed using a Hickman catheter. A very strong, directly proportional correlation was found between performing LUS in 28 and 8 places (ρ=0.909; p&amp;lt;0.001). A significant moderate correlation was also found between both LUS in 28 and 8 places and systolic blood pressure (ρ=0.503; p=0.005 and ρ=0.467; p=0.011, respectively) (Table 1). Neither of the LUS methods statistically correlated with other tested volume markers – overhydration, intracellular and extracellular volume measured with BIA, IVCd in inspiration and expiration and IVC index, or serum NT-proBNP levels. Conclusion In our study, we found a very strong, positive, and significant correlation between performing LUS in 28 regular places and 8 places. Both also moderately correlated with systolic blood pressure. However, we did not find a statistically significant correlation between LUS and other tested volume markers.

#500 Monitoring relative blood volume and calf bioimpedance in hemodialysis patients

Abstract Background and Aims Measurements of relative blood volume (RBV, %) are used to monitor the relative change in blood plasm during hemodialysis (HD). Continuous measurement of calf extracellular volume (cECV) during HD allows the calculation of relative change in cECV (RCE). RCE was defined as the ratio of cECV to its initial value, cECV0 (RCE = 100 × cECV/cECV0, %). The aim of our study was to investigate the relationship between RBV, RCE and the occurrence of intradialytic hypotension (IDH). Method Fifty-five HD patients were studied. We reduced the HD target weight stepwise by 0.1 to 0.2 kg per HD session until clinically defined IDH symptoms occurred. RBV was monitored using the blood volume monitor (BVM, Fresenius Medical Care, Germany). Whole body bioimpedance spectroscopy (wBIS) provided whole body ECV (wECV) and intracellular volume (wICV) pre and post HD. Continuous calf bioimpedance (Hydra 4200, Xitron Technologies, San Diego, CA USA) provided cECV during HD. Pre HD overhydration (OH) was calculated according to whole body composition model (Chamney et al, Am J Clin Nutr 2007; 85:80). Total number of HD sessions in all patients were divided into three groups according to the pre HD OH: 1) normal OH (NOH, OH &amp;lt; 1 L), 2) moderate OH (MOH, 1 ≤ OH &amp;lt; 4 L) and 3) severe OH (SOH, OH ≥ 4 L). Furthermore, patients were stratified by the presence or absence of IDH in each hydration group. Ultrafiltration rate (UFR), pre HD body weight, body mass index (BMI) were measured. Minimal RBV (RBVMin) and minimal RCE (RCEMin) in each HD session were recorded. These measures represent maximum reduction of fluid in the intravascular and interstitial spaces, respectively. Reducing cECV can be considered as refilling fluid from interstitial transferring to intravascular space driving by ultrafiltration. The difference between RCEMin and RBVMin was defined as vascular refilling capacity. Linear mixed-effect logistic regression (LMELR) analysis was applied to explore relationships between IDH with RBVMin, RCEMin, wECV and BMI. Results We studied 621 HD sessions in 55 patients. MOH was present in 57%, SOH in 22% and NOH in 21% of total number of HD sessions respectively. There were significant differences in age, UFR, RBVMin, RCEMin, pre HD wECV, BMI between three groups, while the IDH rate did not differ significantly (Table 1). RBVMin was inversely correlated with UFR (Fig. 1) in all measurements. Pre HD wECV was the only factor associated with IDH in overall measurement. Pre HD wECV was significantly lower in IDH than in non-IDH patients in the NOH group (Fig. 2). In the MOH group, UFR and RCEMin-RBVMin were higher in IDH than in non-IDH patients (Fig. 3a and Fig. 3b). In the SOH group, Pre HD OH is the major factor associated with IDH (Fig. 4). Conclusion This study found that the major factors leading to IDH are 1) lower hydration status; 2) relative higher UFR; and 3) the limited refilling capacity. RBVMin correlated with UFR, but it did not predict IDH. Combined analysis of RBV and calf bioimpedance may provide a means to quantitate the fluid transport between intravascular and interstitial compartments and could add to an early IDH warning system.

The Role of T2 Mapping in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy divided into two types: light-chain (LA) and transthyretin (ATTR) CA. Cardiac magnetic resonance (CMR) has emerged as an important diagnostic tool in CA. While late gadolinium enhancement (LGE), T1 mapping and extracellular volume (ECV) have a consolidate role in the assessment of CA, T2 mapping has been less often evaluated. We aimed to test the value of T2 mapping in the evaluation of CA. This study recruited 70 patients with CA (51 ATTR, 19 AL). All the subjects underwent 1.5 T CMR with T1 and T2 mapping and cine and LGE imaging. Their QALE scores were evaluated. The myocardial T2 values were significantly (p < 0.001) increased in both types of CA compared to the controls. In the AL-CA group, increased T2 values were associated with a higher QALE score. The myocardial native T1 values and ECV were significantly (p < 0.001) higher in the CA patients than in the healthy subjects. Left ventricular (LV) mass, QALE score and ECV were higher in ATTR amyloidosis compared with AL amyloidosis, while the LV ejection fraction was lower (p < 0.001). These results support the concept of the presence of myocardial edema in CA. Therefore, a CMR evaluation including not only myocardial T1 imaging but also myocardial T2 imaging allows for more comprehensive tissue characterization in CA.

Extracellular volume fraction derived from dual-energy CT: a potential predictor for acute pancreatitis after pancreatoduodenectomy.

To investigate the value of extracellular volume (ECV) fraction and fat fraction (FF) derived from dual- energy CT (DECT) for predicting postpancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD). This retrospective study included patients who underwent DECT and PD between April 2022 and September 2022. PPAP was determined according to the International Study Group for Pancreatic Surgery (ISGPS) definition. Iodine concentration (IC) and FF of the pancreatic parenchyma were measured on preoperative DECT. The ECV fraction was calculated from iodine map images of the equilibrium phase. The independent predictors for PPAP were assessed by univariate and multivariable logistic regression analysisand receiver operating characteristic (ROC) curve analysis. Sixty-nine patients were retrospectively enrolled (median age, 60 years; interquartile range, 55-70 years; 47 men). Of these, nine patients (13.0%) developed PPAP. These patients had lower portal venous phase IC, equilibrium phase IC, FF, and ECV fraction, and higher pancreatic parenchymal-to-portal venous phase IC ratio and pancreatic parenchymal-to-equilibrium phase IC ratio, compared with patients without PPAP. After multivariable analysis, ECV fraction was independently associated with PPAP (odd ratio [OR], 0.87; 95% confidence interval [CI]: 0.79, 0.96; p < 0.001), with an area under the curve (AUC) of 0.839 (sensitivity 100.0%, specificity 58.3%). A lower ECV fraction is independently associated with the occurrence of PPAP after PD. ECV fraction may serve as a potential predictor for PPAP after PD. DECT-derived ECV fraction of pancreatic parenchyma is a promising biomarker for surgeons to preoperatively identify patients with higher risk for postpancreatectomy acute pancreatitis after PD and offer selective perioperative management. PPAP is a complication of pancreatic surgery, early identification of higher-risk patients allows for risk mitigation. Lower DECT-derived ECV fraction was independently associated with the occurrence of PPAP after PD. DECT aids in preoperative PAPP risk stratification, allowing for appropriate treatment to minimize complications.

Looking back, moving forward: protein corona of lipid nanoparticles.

Lipid nanoparticles (LNPs) are commonly employed for drug delivery owing to their considerable drug-loading capacity, low toxicity, and excellent biocompatibility. Nevertheless, the formation of protein corona (PC) on their surfaces significantly influences the drug's in vivo fate (such as absorption, distribution, metabolism, and elimination) upon administration. PC denotes the phenomenon wherein one or multiple strata of proteins adhere to the external interface of nanoparticles (NPs) or microparticles within the biological milieu, encompassing ex vivo fluids (e.g., serum-containing culture media) and in vivo fluids (such as blood and tissue fluids). Hence, it is essential to claim the PC formation behaviors and mechanisms on the surface of LNPs. This overview provided a comprehensive examination of crucial aspects related to such issues, encompassing time evolution, controllability, and their subsequent impacts on LNPs. Classical studies of PC generation on the surface of LNPs were additionally integrated, and its decisive role in shaping the in vivo fate of LNPs was explored. The mechanisms underlying PC formation, including the adsorption theory and alteration theory, were introduced to delve into the formation process. Subsequently, the existing experimental outcomes were synthesized to offer insights into the research and application facets of PC, and it was concluded that the manipulation of PC held substantial promise in the realm of targeted delivery.

A Comparison Study on the Metabolites in PC-3, RWPE-1, and Chrysin-Treated PC-3 Cells

Prostate cancer is frequently diagnosed and the leading cause of death in men worldwide. Prostate-specific antigen (PSA) blood tests and biopsies are the primary methods for diagnosing prostate cancer; however, their accuracy is less than 50%. Therefore, there is a need to develop diagnostic tests that minimize patient discomfort during examination and adequate biomarkers that are more accurate, sensitive, and specific for the detection of prostate cancer. This study investigated the application of metabolomics to identify biomarkers in prostate cancer biofluids. In addition, changes in prostate cancer metabolite levels induced by chrysin, a natural anticancer compound, were evaluated and compared with those in non-treated prostate cancer cells. Gas chromatography-mass spectrometry (GC-MS)-based metabolomic profiling was performed to investigate the differences in metabolic alterations among prostate cancer, normal prostate, and chrysin-treated prostate cancer cells. Pairwise comparisons of the extracellular fluid metabolomes were performed using principal component analysis (PCA), partial least squares–discriminant analysis (PLS-DA), and Student’s t-test. The results revealed significantly different patterns among the metabolite groups, including alcohols, amino acids, carboxylic acids, organic acids, sugars, and urea. The RWPE-1- and chrysin-treated PC-3 (PC-3 Chr) cell groups showed similar tendencies for 23 metabolites, while the groups showed significant differences from the PC-3 group. Most amino acids showed higher concentrations in PC-3 cells than in the normal cell line RWPE-1 cells and PC-3 Chr cells. Our results revealed that GC-MS might be an effective diagnostic tool to detect prostate cancer and contribute to finding new tumor markers for prostate cancer as the basis for new ideas.

VENTRICULAR ARRHYTHMIAS IN A UNEXPECTED CARDIAC MAGNETIC RESONANCE

Abstract Background Electrical storm in a widespread inflammation of the myocardium represent a very challenge condition and recognizes a broad spectrum of etiology. Case Presentation A 59–year–old man, without significant prior medical history, came to our attention because, following an emergent hernioplasty procedure, he displayed anterior ST–segment elevation and elevated troponin levels (150.000 ng/L). An echocardiogram revealed an estimated left ventricular ejection fraction (EF) of 39% with anterior hypokinesia. Coronary angiography showed no abnormalities. Cardiac magnetic resonance imaging demonstrated ring–like edema and ring–like late gadolinium enhancement in the left ventricle on T2–weighted and PSIR sequences, with no involvement of the right ventricle. Additionally, there was an increase in extracellular volume. Despite several laboratory tests to investigate infectious or autoimmune causes, the etiology remained inconclusive. To further explore the cause, an endomyocardial biopsy was performed. However, the patient experienced an unstable electrical storm three days later. Management Recurrent ventricular tachycardia (VT) was initially treated with esmolol, amiodarone, and procainamide, but with limited success. Due to VT–induced hemodynamic instability, the patient was sedated with propofol and intubated. Endomyocardial biopsy (EMB) confirmed lymphocytic myocarditis. In light of the hemodynamic instability and refractory electrical storm, the patient was promptly cannulated for veno–arterial extracorporeal membrane oxygenation (VA–ECMO) and started on methylprednisolone. Although there was an apparent resolution of VT, the patient experienced new episodes, necessitating percutaneous stellate ganglion block and an upgraded treatment plan that included mycophenolate mofetil. Given the high burden of arrhythmias, severe ventricular dysfunction, and the lack of response to medications, the patient is now awaiting cardiac transplantation. Conclusion Transmural edema and ring–like late gadolinium enhancement (LGE) in the early phase are predictors of a poor prognosis. In cases of hemodynamic deterioration and refractory electrical storms, it is crucial to promptly initiate mechanical support. Cardiac transplantation remains the sole treatment option for individuals who do not respond to antiarrhythmic and immunosuppressive drugs.

Diagnostic performance of dynamic contrast-enhanced magnetic resonance imaging parameters and serum tumor markers in rectal carcinoma prognosis.

Rectal carcinoma (RC), one of the most common malignancies globally, presents an increasing incidence and mortality year by year, especially among young people, which seriously affects the prognosis and quality of life of patients. At present, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and serum carbohydrate antigen 19-9 (CA19-9) and CA125 Levels have been used in clinical practice to evaluate the T stage and differentiation of RC. However, the accuracy of these evaluation modalities still needs further research. This study explores the application and value of these methods in evaluating the T stage and differentiation degree of RC. To analyze the diagnostic performance of DCE-MRI parameters combined with serum tumor markers (TMs) in assessing pathological processes and prognosis of RC patients. A retrospective analysis was performed on 104 RC patients treated at Yantai Yuhuangding Hospital from May 2018 to January 2022. Patients were categorized into stages T1, T2, T3, and T4, depending on their T stage and differentiation degree. In addition, they were assigned to low (L group) and moderate-high differentiation (M + H group) groups based on their differentiation degree. The levels of DCE-MRI parameters and serum CA19-9 and CA125 in different groups of patients were compared. In addition, the value of DCE-MRI parameters [volume transfer constant (Ktrans), rate constant (Kep), and extravascular extracellular volume fraction (Ve) in assessing the differentiation and T staging of RC patients was discussed. Furthermore, the usefulness of DCE-MRI parameters combined with serum CA19-9 and CA125 Levels in the evaluation of RC differentiation and T staging was analyzed. Ktrans, Ve, CA19-9 and CA125 were higher in the high-stage group and L group than in the low-stage group and M + H Group, respectively (P < 0.05). The areas under the curve (AUCs) of the Ktran and Ve parameters were 0.638 and 0.694 in the diagnosis of high and low stages, respectively, and 0.672 and 0.725 in diagnosing moderate-high and low differentiation, respectively. The AUC of DCE-MRI parameters (Ktrans + Ve) in the diagnosis of high and low stages was 0.742, and the AUC in diagnosing moderate-high and low differentiation was 0.769. The AUCs of CA19-9 and CA-125 were 0.773 and 0.802 in the diagnosis of high and low stages, respectively, and 0.834 and 0.796 in diagnosing moderate-high and low differentiation, respectively. Then, we combined DCE-MRI (Ktrans + Ve) parameters with CA19-9 and CA-125 and found that the AUC of DCE-MRI parameters plus serum TMs was 0.836 in the diagnosis of high and low stages and 0.946 in the diagnosis of moderate-high and low differentiation. According to the Delong test, the AUC of DCE-MRI parameters plus serum TMs increased significantly compared with serum TMs alone in the diagnosis of T stage and differentiation degree (P < 0.001). The levels of the DCE-MRI parameters Ktrans and Ve and the serum TMs CA19-9 and CA125 all increase with increasing T stage and decreasing differentiation degree of RC and can be used as indices to evaluate the differentiation degree of RC in clinical practice. Moreover, the combined evaluation of the above indices has a better effect and more obvious clinical value, providing important guiding importance for clinical condition judgment and treatment selection.