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Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration. Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group. Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.

Renal sodium and water retention with resulting extracellular volume expansion and redistribution are hallmark features of heart failure syndromes. However, congestion assessment, monitoring, and treatment represent a real challenge in daily clinical practice. This document reviewed historical and contemporary evidence of available methods for determining volume status and discuss pharmacological aspects and pathophysiological principles that underlie diuretic use.

The article deals with the study of nutritional status in patients with chronic inflammatory bowel disease (CIBD) using bioimpedancemetry. 40 patients with CIBD were examined. The high prevalence of deviations in the percentage of fat mass in the body (87.5 %) has been detected, with a predominance of nutritional deficiency (65.0 %) associated with a decrease in the body’s adaptive capabilities and severe course of the disease. 70.0 % of patients were characterized by redistribution of water sectors of the body due to increased amount of extracellular fluid and reduced amount of intracellular fluid, which was more significant in patients with increased nutritional status compared to patients with nutritional deficiency. More expressed changes of the component composition of the body were in patients with Crohn’s disease.

BACKGROUND The development of heart failure is associated with fluid balance, including that of extracellular water (ECW) and intracellular water (ICW). This study determined whether sodium-glucose cotransporter 2 inhibitors affect fluid balance and improve heart failure in patients after acute myocardial infarction. METHODS AND RESULTS EMBODY was a prospective, randomized, double-blinded, placebo-controlled trial of Japanese patients with acute myocardial infarction and type 2 diabetes. Overall, 55 patients who underwent bioelectrical impedance analysis were randomized to receive once daily 10 mg empagliflozin or placebo 2 weeks after acute myocardial infarction onset. We investigated the time course of body fluid balance measured using the bioelectrical impedance analysis device, InBody. The primary end points were changes in body fluid balance from weeks 0 to 24. Changes between baseline and week 24 in the empagliflozin and placebo groups were -0.21 L (P = .127) and +0.40 L (P = .001) in ECW (P = .001) and -0.23 L (P = .264) and +0.74 L (P < .001) in ICW (P < .001), respectively. In a stratified analysis, the rise in ECW and ICW was significantly attenuated in the empagliflozin group in contrast to the placebo group in participants with a body mass index of 25 or higher but not in those with a body mass index of less than 25. CONCLUSIONS Early sodium-glucose cotransporter 2 inhibitor administration may attenuate changes in ECW and ICW.

As stated in Chap. 6, the maintenance of extracellular fluid (ECF) volume is dependent on the extracellular concentration of Na+ ([Na+]). An increase in total body Na+ causes an expansion in ECF volume, and a decrease in total body Na+ reduces ECF volume. Most of the critically ill patients and patients with less availability of salt and water develop volume contraction, because it is rather difficult to induce volume contraction in humans with normal renal function. The signs and symptoms of volume contraction depend on the rapidity of Na+ loss. Sudden loss of Na+ causes a marked reduction in blood pressure and cardiac output, whereas slow and sustained loss results in a slight decrease in blood pressure. Pure water loss results in hypertonicity with high serum [Na+], whereas loss of both Na+ and water leads to low blood pressure.

BACKGROUND Bioelectrical impedance analysis (BIA) devices have been advocated to guide volume management in hemodialysis (HD) patients. We hypothesized that understanding the dynamics of fluid shifts in different body segments may provide additional insight on preventive measures to reduce the risk of intradialytic hypotension. METHODS A prospective observational study was conducted among 42 HD patients at risk of hypotension who were admitted as emergencies inpatient. RESULTS A total of 191 BIA measurements were made during the 42 HD sessions, and hypotension occurred during 52 measurements (27%). The extracellular water (ECW) to intracellular water ratio (EIR) was measured in different body segments and declined significantly only in the non-access arm with increasing HD session duration (β = -0.04; 95% confidence interval (CI): -0.05 to -0.03, p

Dietary interventions can change metabolite levels in the tumour microenvironment, which might then affect cancer cell metabolism to alter tumour growth1–5. Although caloric restriction (CR) and a ketogenic diet (KD) are often thought to limit tumour progression by lowering blood glucose and insulin levels6–8, we found that only CR inhibits the growth of select tumour allografts in mice, suggesting that other mechanisms contribute to tumour growth inhibition. A change in nutrient availability observed with CR, but not with KD, is lower lipid levels in the plasma and tumours. Upregulation of stearoyl-CoA desaturase (SCD), which synthesises monounsaturated fatty acids, is required for cancer cells to proliferate in a lipid-depleted environment, and CR also impairs tumour SCD activity to cause an imbalance between unsaturated and saturated fatty acids to slow tumour growth. Enforcing cancer cell SCD expression or raising circulating lipid levels through a higher-fat CR diet confers resistance to the effects of CR. By contrast, although KD also impairs tumour SCD activity, KD-driven increases in lipid availability maintain the unsaturated to saturated fatty acid ratios in tumours, and changing the KD fat composition to increase tumour saturated fatty acid levels cooperates with decreased tumour SCD activity to slow tumour growth. These data suggest that diet-induced mismatches between tumour fatty acid desaturation activity and the availability of specific fatty acid species determine whether low glycaemic diets impair tumour growth. Lien et al. show that low glycemic diets can reduce tumour growth by deregulating lipid metabolism.

The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P

Aims In this study, we aimed to investigate whether body composition analysis (BCA) derived from bioelectrical impedance vector analysis (BIVA) could be used to monitor the hydration status of patients with acute heart failure (AHF) during intensified diuretic therapy. Methods and results This observational, single‐centre study involved a novel, validated eight‐electrode segmental body composition analyser to perform BCA derived from BIVA with an alternating current of 100 μA at frequencies of 5, 7.5, 50, and 75 kHz. The BCA‐derived and BIVA‐derived parameters were estimated and compared with daily body weight measurements in hospitalized patients with AHF. A total of 867 BCA and BIVA assessments were conducted in 142 patients (56.3% men; age 76.8 ± 10.7 years). Daily changes in total body water (TBW) and extracellular water (ECW) were significantly associated with changes in body weight in 62.2% and 89.1% of all measurements, respectively (range, ±1 kg). Repeated measures correlation coefficients between weight loss and TBW loss resulted with rho 0.43, P 0.01, CI [0.67, 0.75] for ECW loss. Between the first and last assessments, the mean weight loss was −2.5 kg, compared with the −2.6 L mean TBW loss and −1.7 L mean ECW loss. BIVA revealed an increase in mean Resistance R and mean Reactance Xc across all frequencies, with the subsequent reduction in body fluid (including corresponding body weight) between the first and last assessments. Conclusions Body composition analysis derived from BIVA with a focus on ECW is a promising approach to detect changes in hydration status in patients undergoing intensified diuretic therapy. Defining personalized BIVA reference values using bioelectrical impedance devices is a promising approach to monitor hydration status.

Background Disruption of cerebrospinal fluid (CSF)/interstitial fluid (ISF) exchange in the spinal cord is likely to contribute to central nervous system (CNS) diseases that involve abnormal fluid accumulation, including spinal cord oedema and syringomyelia. However, the physiological factors that govern fluid transport in the spinal cord are poorly understood. The aims of this study were to determine the effects of cardiac pulsations and respiration on tracer signal increase, indicative of molecular movement following infusion into the spinal cord grey or white matter. Methods In Sprague Dawley rats, physiological parameters were manipulated such that the effects of spontaneous breathing (generating alternating positive and negative intrathoracic pressures), mechanical ventilation (positive intrathoracic pressure only), tachycardia (heart atrial pacing), as well as hypertension (pharmacologically induced) were separately studied. Since fluid outflow from the spinal cord cannot be directly measured, we assessed the molecular movement of fluorescent ovalbumin (AFO-647), visualised by an increase in tracer signal, following injection into the cervicothoracic spinal grey or white matter. Results Tachycardia and hypertension increased AFO-647 tracer efflux, while the concomitant negative and positive intrathoracic pressures generated during spontaneous breathing did not when compared to the positive-pressure ventilated controls. Following AFO-647 tracer injection into the spinal grey matter, increasing blood pressure and heart rate resulted in increased tracer movement away from the injection site compared to the hypotensive, bradycardic animals (hypertension: p = 0.05, tachycardia: p Conclusions Arterial pulsations have profound effects on spinal cord interstitial fluid homeostasis, generating greater tracer efflux than intrathoracic pressure changes that occur over the respiratory cycle, demonstrated by increased craniocaudal CSF tracer movement in the spinal cord parenchyma.

Background: Adequate assessment of fluid status is an imperative objective in the management of HD patients. An inaccurate assessment of dry weight leads to many complications. Objective: The aim was to assess applicability of clinical using inferior vena cava (IVC) and lung ultrasonography to assess dry weight and the adequacy of fluid removal in hemodialysis children with special relation between acute and chronic renal failure. Patients and methods: 75 children were classified into two groups: Group (1): Chronic renal failure and group (2): Acute renal failure. Results: A statistically positive significant correlation between percent of weight loss after dialysis among the studied patients and all of serum ferritin, creatinine, phosphorus and iron. There was statistically negative significant correlation between percent of weight loss after dialysis among the studied patients and serum creatinine. There was statistically significant negative correlation between percent of weight loss after dialysis among the studied patients and SPAP. There was statistically non-significant correlation between percent of weight loss after dialysis among the studied patients and percent change in IVC inspiratory diameter, expiratory diameter, collapse index and B lines. There was statistically significant difference between the studied groups and expiratory IVCD, collapse index before and after dialysis, difference in B lines. Conclusion: Lung ultrasound is an accurate and sensitive method of quantifying subclinical fluid overload in children on dialysis before its clinical manifestation. IVC measurement is reliable to assess intravascular fluid overload in children on HD and was not correlated with extracellular fluid volume as need more time (2-3h) after dialysis and maneuver difficult with young age.

Введение. Концентрация Na+ и K+ в клетке и внеклеточной жидкости обусловливает фундаментальные свойства организма. В работе использовано Na+/К+ отношение сыворотки крови как патофизиологический критерий состояния человека при сходной патологии легких, но генетически разных орфанных заболеваниях. Цель исследования - изучение соотношения концентрации ионов Na+ и K+ в сыворотке крови как интегрального патофизиологического параметра базовой функции клеток при орфанных заболеваниях сопряженных с патологией легких. Методика. Обследованы 99 детей, в том числе 50 с 3 формами орфанной патологии легких. Среди них 24 ребенка с муковисцидозом (МВ), 15 детей с первичным иммунодефицитом (ПИД), 11 - с первичной цилиарной дискинезией (ПЦД). Контрольную группу- составили15 здоровых детей, группу сравнения - 34 пациента с внебольничной пневмонией, в том числе 15 с тяжелым течением. Возраст обследованных от 3 мес до 17 лет. Концентрация ионов Na+, K+, Cl-, измерялась ионоселективными электродами на анализаторе Erba XL-200, креатинина - кинетическим методом по реакции Яффе без депротеинизации на анализаторе Erba XL-200. Результаты. Концентрация Na+ и К+ в сыворотке крови у пациентов всех групп соответствовала стандартам нормы, однако расчет Na+/К+ отношения выявил статистически значимые отличия от показателей контрольной группы (30.40 ± 0.48) у пациентов с МВ, ПИД, ПЦД и при внебольничной пневмонии средней степени тяжести - 32.7±0.8, 33.2±0.9, 32.83±0.8 и 33±1, соответственно, (р Introduction. Concentrations of Na+ and K+ in the cell and in the extracellular fluid determine fundamental properties of the organism. The study used the blood serum Na+/K+ ratio as a pathophysiological criterion for the state of patients with similar pathologies of the lungs but with genetically different orphan diseases. The aim of the study was to evaluate the Na+/K+ concentration ratio in the blood serum as an integral pathophysiological parameter of the basic cell function in orphan diseases associated with lung pathology. Methods. 99 children were examined, including 24 with cystic fibrosis (CF), 15 with primary immunodeficiency (PIDs), and 11 with primary ciliary dyskinesia (PCD). The control group consisted of 15 healthy children and the comparison group consisted of 34 patients with community-acquired pneumonia, including 15 with severe disease. The patients aged from 3 mos. to 17 years. Concentrations of Na+, K+, and Cl- were measured with ion-selective electrodes on an Erba XL-200 analyzer; creatinine was measured by the kinetic method using the Jaffe reaction without deproteinization on an Erba XL-200 analyzer. Results. Concentrations of Na+ and K+ in blood serum in all groups corresponded to normal, standard values. The Na+/K+ ratio was 30.4±0.48 in healthy people, 32.7±0.8, 33.2±0.9, 32.83±0.8, and 33±1 in patients with CF, PIDs, PCD, or community-acquired pneumonia of moderate severity, respectively (р

Objective Although fluid resuscitation is the cornerstone of treatment for sepsis, the role of body water status in sepsis is poorly understood. This study aimed to understand how body water and its distribution are modified in patients with sepsis and those with non-septic infection compared to healthy individuals.Methods Two groups of adults presumed to have non-septic infection (n=87) and sepsis (n=54) were enrolled in this prospective study in a single emergency department, and they were compared to sex-, age-, and height-matched (1:3 ratio) healthy controls (n=11,190) from retrospective data in a health promotion center. Total body water (TBW), intracellular water (ICW), and extracellular water (ECW), determined using direct segmental multi-frequent bioelectrical impedance analysis (InBody S10) were expressed as indices for normalization by body weight (BW). The ratio of ECW to TBW (ECW/TBW) was evaluated to determine body water distribution.Results TBW/BW, ICW/BW, and ECW/BW were significantly higher in the non-septic infection group than in the healthy group (P

Introduction: Isolated ultrafiltration (IUF) is an alternative treatment for diuretic-resistant patients with fluid retention. Although hemodialysis (HD) predominantly decreases extracellular water (ECW), the impact of IUF on fluid distribution compared with HD remains unclear. Methods: We compared the effect of HD (n = 22) and IUF (n = 10) sessions on the body fluid status using a bioimpedance analysis device (InBody S10). Results: The total ultrafiltration volume was similar between HD and IUF (HD 2.5 ± 0.3 vs. ICF 2.1 ± 0.3 L/session, p = 0.196). The reduction rate of ECW was significantly higher than that of intracellular water (ICW) after HD (ECW −7.9% ± 0.8% vs. ICW −3.0% ± 0.9%, p < 0.001) and IUF (ECW −5.8% ± 0.9% vs. ICW -3.6% ± 0.8%, p = 0.048). However, the change in the ratio of ECW to total body water in HD was significantly larger than that in IUF (HD −3.2% ± 0.3% vs. ICF −1.1% ± 0.4%, p < 0.001). The reduction rates in serum tonicity (effective osmolality) were higher after HD than after IUF (HD −1.8% ± 0.5% vs. IUF −0.6% ± 0.2%, p = 0.052). Among the components of effective osmolality, the reduction rates of serum K+ and glucose levels after HD were significantly higher than those after IUF (serum K+: HD −30.5% ± 1.6% vs. IUF −0.5% ± 3.8%, p < 0.001; serum glucose: HD −15.4% ± 5.0% vs. IUF 0.7% ± 4.8%, p = 0.026), while the serum Na+ level was slightly and similarly reduced (HD −0.8% ± 0.4% vs. IUF −0.8% ± 0.4%, p = 0.500). The reduction in the osmolal gap value (measured osmolality–calculated osmolarity) was significantly greater after HD sessions than after IUF sessions (HD −12.4 ± 1.4 vs. IUF 2.0 ± 1.0 mOsm/kg, p = 0.001). Conclusion: The extracellular fluid reduction effect of HD is stronger than that of IUF. The different changes in effective osmolality and osmolal gap after HD and IUF sessions may be related to the different effects of HD and IUF on fluid distribution.

In animal and human neonates, expansion of the extracellular fluid volume is associated with "wet" lung and poor respiratory outcomes. To define fluid status changes during the transition from fetal to neonatal life in infants of diabetic mothers (IDM), we conducted a single-centre (Policlinico Abano Terme, Abano Terme, Italy) study of 66 IDM and a 1:2 matched control group from January 1 to September 30, 2020. Fluid status changes were assessed by computing Δ Hct from umbilical cord blood at birth and capillary heel Hct at 48 h, accounting for body weight decrease. IDM presented with significantly lower cord blood Hct levels in comparison to controls (47.33 ± 4.52 vs 50.03 ± 3.51%, p < 0.001), mainly if delivered by elective cesarean Sect. (45.01 ± 3.77 vs 48.43 ± 3.50%, p = 0.001). Hct levels at 48 h were comparable (55.18 ± 5.42 vs 54.62 ± 7.41%, p = 0.703), concurrently with similar body weight decrease (- 217.21 ± 113.34 vs - 217.51 ± 67.28 g, p = 0.614). This supports significantly higher ∆ Hct in IDM (5.13 ± 5.24 vs 7.29 ± 6.48, p < 0.01) and extra circulating fluid loss of 2-3%.Conclusion: Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung. What is Known: • In neonates, evidence suggests that expansion of the extracellular fluid volume prior to the postnatal diuresis is associated with poor respiratory outcomes. What is New: • Gestational diabetes is associated with an excess of circulating fluids during the transition from fetal to neonatal life, challenging the current assumption that is per se at risk of wet lung.

Background Quantification of non-ischemic myocardial scar remains a challenge due to the patchy diffuse nature of fibrosis. Extracellular volume (ECV) to guide late gadolinium enhancement (LGE) analysis may achieve a robust scar assessment. Methods Three cohorts of 80 non-ischemic-training, 20 non-ischemic-validation, and 10 ischemic-validation were prospectively enrolled and underwent 3.0 Tesla cardiac MRI. An ECV cutoff to differentiate LGE scar from non-scar was identified in the training cohort from the receiver-operating characteristic curve analysis, by comparing the ECV value against the visually-determined presence/absence of the LGE scar at the highest signal intensity (SI) area of the mid-left ventricle (LV) LGE. Based on the ECV cutoff, an LGE semi-automatic threshold of n-times of standard-deviation (n-SD) above the remote-myocardium SI was optimized in the individual cases ensuring correspondence between LGE and ECV images. The inter-method agreement of scar amount in comparison with manual (for non-ischemic) or full-width half-maximum (FWHM, for ischemic) was assessed. Intra- and inter-observer reproducibility were investigated in a randomly chosen subset of 40 non-ischemic and 10 ischemic cases. Results The non-ischemic groups were all female with the HIV positive rate of 73.8% (training) and 80% (validation). The ischemic group was all male with reduced LV function. An ECV cutoff of 31.5% achieved optimum performance (sensitivity: 90%, specificity: 86.7% in training; sensitivity: 100%, specificity: 81.8% in validation dataset). The identified n-SD threshold varied widely (range 3 SD–18 SD), and was independent of scar amount (β = −0.01, p = 0.92). In the non-ischemic cohorts, results suggested that the manual LGE assessment overestimated scar (%) in comparison to ECV-guided analysis [training: 4.5 (3.2–6.4) vs. 0.92 (0.1–2.1); validation: 2.5 (1.2–3.7) vs. 0.2 (0–1.6); P P Conclusions ECV-guided LGE analysis is a robust scar quantification method for a non-ischemic cohort. Trial registration ClinicalTrials.gov; NCT00000797, retrospectively-registered 2 November 1999; NCT02501811, registered 15 July 2015.

Aims/Introduction Body fluid volume imbalance is common in patients with kidney failure, and is associated with all‐cause mortality. This study aimed to investigate the association between fluid volume imbalance and albuminuria in patients with type 2 diabetes mellitus without kidney failure. Materials and Methods Using data from one cohort study, a baseline cross‐sectional study of 432 participants and a longitudinal cohort study of 368 participants who could follow up was carried out. Body fluid imbalance was determined by measuring the extracellular water (ECW)‐to‐intracellular water (ICW) ratio (ECW/ICW) using bioelectrical impedance analysis. A change in the urinary albumin‐to‐creatinine ratio (ACR) was defined as the ratio of urinary ACR at follow up to that at baseline. The ECW/ICW ratio was compared with the level of albuminuria. Results In this cross‐sectional study, the ECW/ICW ratio increased with the level of albuminuria. There was an association between the ECW/ICW ratio and logarithms of urinary ACR after adjusting for covariates (β = 0.205, P 300 mg/gCr, was 0.648 (area under the curve 0.78, 95% confidence interval 0.58–0.90). Conclusions The ECW/ICW ratio is independently associated with the level of albuminuria in patients with type 2 diabetes mellitus without kidney failure. This reinforces the importance of monitoring fluid balance in patients with type 2 diabetes mellitus., Fluid imbalance occurred in diabetes patients without kidney failure, and was associated with the level of albuminuria. The extracellular water to intracellular water ratio is independently associated with changes in albuminuria in patients with type 2 diabetes mellitus without kidney failure. Clinicians need to pay more attention to monitoring the fluid status among patients with type 2 diabetes mellitus, and maintaining fluid balance in the early stage of diabetic kidney disease.

The study group consisted of 20 men of various ages (14-69 years) and weight. To assess the processes of autophagy, the activity of the protein Beclin-1 was used. In individuals with normal body weight, the presence of positive reliable correlations between the level of beclin-1 and extracellular water was revealed (r = 0.96; p

Background Rodent brain slices—particularly hippocampal slices—are widely used in experimental investigations of epileptiform activity. Oxygenated artificial cerebrospinal fluid (ACSF) is used to maintain slices in vitro. Physiological or standard ACSF containing 3–3.5 mM K+, 1–2 mM Mg2+, and 1–3 mM Ca2+ generally does not induce population epileptiform activity, which can be induced by ACSF with high K+ (8–10 mM), low Mg2+, or low Ca2+ alone or in combination. While low-Mg2+ ACSF without intentionally added Mg salt but with contaminating Mg2+ (≤ 50–80 µM) from other salts can induce robust epileptiform activity in slices, it is unclear whether such epileptiform activity can be achieved using ACSF with moderately decreased Mg2+. To explore this issue, we examined the effects of moderately modified (m)ACSF with 0.8 mM Mg2+, 1.3 mM Ca2+, and 5.7 mM K+ on induction of epileptiform discharges in mouse hippocampal slices. Results Hippocampal slices were prepared from young (21–28 days old), middle-aged (13–14 months old), and aged (24–26 months old) C57/BL6 mice. Conventional thin (0.4 mm) and thick (0.6 mm) slices were obtained using a vibratome and pretreated with mACSF at 35–36 °C for 1 h prior to recordings. During perfusion with mACSF at 35–36 °C, spontaneous or self-sustained epileptiform field potentials following high-frequency stimulation were frequently recorded in slices pretreated with mACSF but not in those without the pretreatment. Seizure-like ictal discharges were more common in thick slices than in thin slices. Conclusions Prolonged exposure to mACSF by pretreatment and subsequent perfusion can induce epileptiform field potentials in mouse hippocampal slices.

Background Myocardial fibrosis and left ventricular (LV) longitudinal strain are independently associated with adverse clinical outcomes. However, the relationship between tissue properties and strain indices as well as their collective impact on outcomes are yet to be fully elucidated. We aim to investigate the relationship between LV global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) with extracellular volume (ECV) and their collective impact. Methods Consecutive patients referred for clinical cardiovascular magnetic resonance (CMR) due to cardiomyopathy were prospectively enrolled. All patients underwent CMR with T1 mapping. ECV was calculated incorporating native and post-contrast T1 as well as hematocrit. LV GLS, GCS, and GRS were assessed by feature tracking. Hazard ratios and Kaplan–Meier curves were produced to assess the association between strains and T1 mapping indices with a composite outcome of all-cause mortality and hospitalized heart failure. Results The study consisted of 259 patients with mixed referring diagnoses of non-ischemic/ischemic cardiomyopathy and 21 normal controls. Decreased GLS, GCS and GRS were associated with increased ECV, increased native T1, and reduced post-contrast T1 in a dose dependent manner when T1 or ECV was in the abnormal range. After a mean follow-up of 31 ± 23 months, 41 events occurred including 37 heart failure admissions and 4 deaths. Kaplan–Meier plots demonstrated that reduced strains were associated with reduced event-free survival predominantly in patients with increased ECV (≥ 28.3%). The worst outcome was among those with both reduced strains and increased ECV. In the multivariable models, increased ECV, reduced post-contrast T1 and reduced strains in all 3 directions remained predictors of outcome risk, respectively. Conclusion Our findings highlight the intrinsic link between altered CMR tissue properties and impaired myocardial mechanical performance and additionally demonstrate improved risk stratification by characterizing tissue property among patients with reduced strain.

Background Extracellular DNA (e-DNA) and neutrophil extracellular traps (NETs) are linked to asthmatics airway inflammation. However, data demonstrating the characterization of airway inflammation associated with excessive e-DNA production and its impact on asthma outcomes are limited. Objective To characterize the airway inflammation associated with excessive e-DNA production and its association with asthma control, severe exacerbations and pulmonary function, particularly, air trapping and small airway dysfunction. Methods We measured e-DNA concentrations in induced sputum from 134 asthma patients and 28 healthy controls. We studied the correlation of e-DNA concentrations with sputum neutrophils, eosinophils and macrophages and the fractional exhaled nitric oxide (FeNO). Lung function was evaluated using spirometry, body plethysmography, impulse oscillometry and inert gas multiple breath washout. We stratified patients with asthma into low-DNA and high-DNA to compare lung function impairments and asthma outcomes. Results Patients with severe asthma had higher e-DNA concentration (54.2 ± 42.4 ng/µl) than patients with mild-moderate asthma (41.0 ± 44.1 ng/µl) or healthy controls (26.1 ± 16.5 ng/µl), (all p values 1) and small airways (FEF50%, FEF25–75), increased air trapping (RV, RV/TLC), increased small airway resistance (R5-20, sReff), decreased lung elasticity (X5Hz) and increased ventilation heterogeneity (LCI), (all P values Conclusion Increased production of extracellular DNA in the airway characterizes a subset of neutrophilic asthma patients who have broad lung function impairments, poor symptom control and increased risk of severe exacerbations.

This study used cardiovascular magnetic resonance (CMR) to evaluate whether elevated extracellular volume (ECV) was associated with mitral valve prolapse (MVP) or if elevated ECV was a consequence of remodeling independent of primary mitral regurgitation (MR) etiology.Replacement fibrosis in primary MR is more prevalent in MVP; however, data on ECV as a surrogate for diffuse interstitial fibrosis in primary MR are limited.Patients with chronic primary MR underwent comprehensive CMR phenotyping and were stratified into an MVP cohort (2 mm leaflet displacement on a 3-chamber cine CMR) and a non-MVP cohort. Factors associated with ECV and replacement fibrosis were assessed. The association of ECV and symptoms related to MR and clinical events (mitral surgery and cardiovascular death) was ascertained.A total of 424 patients with primary MR (229 with MVP and 195 non-MVP) were enrolled. Replacement fibrosis was more prevalent in the MVP cohort (34.1% vs. 6.7%; p 0.001), with bi-leaflet MVP having the strongest association with replacement fibrosis (odds ratio: 10.5; p 0.001). ECV increased with MR severity in a similar fashion for both MVP and non-MVP cohorts and was associated with MR severity but not MVP on multivariable analysis. Elevated ECV was independently associated with symptoms related to MR and clinical events.Although replacement fibrosis was more prevalent in MVP, diffuse interstitial fibrosis as inferred by ECV was associated with MR severity, regardless of primary MR etiology. ECV was independently associated with symptoms related to MR and clinical events. (DeBakey Cardiovascular Magnetic Resonance Study [DEBAKEY-CMR]; NCT04281823).

Enhanced muscle echo intensity (EI) with ultrasound imaging and a higher extracellular water-to-intracellular water (ECW/ICW) ratio with segmental-bioelectrical impedance spectroscopy (S-BIS) represent muscle quality loss. This study aimed to clarify quadriceps muscle degeneration characteristics, focusing on muscle quality changes in patients with knee osteoarthritis (OA). Forty-one women with knee OA (mean age, 71.4±6.0 years) and 27 healthy women (mean age, 75.6±4.9 years) participated. Ultrasonography was used to evaluate the muscle thickness (MT) and the EI of each quadriceps compartment. The ECW/ICW ratio was obtained by S-BIS. MT, EI, and ECW/ICW ratio differences between the two groups were tested using univariate analysis of variance, adjusting for age and body mass index. Logistic regression analyses were performed with the group as the dependent variable, and the MT and EI of the vastus medialis (VM) and the ECW/ICW ratio as independent variables. Patients with knee OA had a significant decrease in VM MT, enhanced VM, and vastus intermedius EIs and a higher ECW/ICW ratio compared with healthy participants. Logistic regression analysis showed that the VM EI (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.06–1.35) and the ECW/ICW ratio were independently associated with knee OA (OR, 1.19; 95% CI, 1.00–1.42). VM EI and the ECW/ICW ratio, rather than VM MT, characterised quadriceps muscle degeneration in patients with knee OA. Therefore, enhanced EI and a higher ECW/ICW ratio are helpful clinical signs for detecting muscle degeneration in patients with knee OA.

Introduction: Serum cancer antigen 125(SeCA125) has been reported to be increased in patients with heart failure and correlate with both extracellular water (ECW) overload and poor prognosis. Ultrafiltration failure and ECW overload are a major cause of peritoneal dialysis (PD) technique failure. We wished to determine whether SeCA125 could also be a marker of volume status in PD patients. Methods: We contemporaneously measured SeCA125, serum N terminal brain natriuretic peptide (NTproBNP) and ECW by bioimpedance in adult PD patients attending for outpatient assessment of peritoneal membrane function. Results: The median SeCA125 was 19 (12–33) U/mL in 489 PD patients, 61.3% male, median age 61.5 (interquartile range 50–75) years. SeCA125 was positively associated with the ratio of ECW/total body water (TBW) ( r = 0.29, p Conclusion: Heart failure studies have reported SeCA125 is a marker of ECW overload. Our retrospective analysis suggests that SeCA125 is also associated with ECW volume in PD patients. Further studies are required to determine whether serial measurements of SeCA125 trend with changes in ECW status in PD patients and can be used to aid volume assessments.

Pituitary adenylate cyclase-activating polypeptide (PACAP) plays an essential role in the modulation of astrocyte functions. Although lactate secretion from astrocytes contributes to many forms of neuronal plasticity in the central nervous system, including fear learning and memory, the role of PACAP in lactate secretion from astrocytes is unclear. The amygdala and hippocampus of PACAP (+ / +) and PACAP (−/−) mice were acquired 1 h after memory acquisition and recall in the passive avoidance test. The concentration of glycogen and lactate in these regions was measured. The concentration of lactate in the hippocampus's extracellular fluid was also measured by microdialysis during memory acquisition or intracerebroventricular administration of PACAP. We observed that memory acquisition caused a significant decrease in glycogen concentration and increased lactate concentration in the PACAP (+ / +) mice's hippocampus. However, memory acquisition did not increase in the lactate concentration in PACAP (−/−) mice's hippocampus. Further, memory retrieval evoked lactate production in the amygdala and the hippocampus of PACAP (+ / +) mice. Still, there was no significant increase in lactate concentration in the same regions of PACAP (−/−) mice. In vivo microdialysis in rats revealed that the hippocampus's extracellular lactate concentration increased after a single PACAP intracerebroventricular injection. Additionally, the hippocampus's extracellular lactate concentration increased with the memory acquisition in PACAP (+ / +) mice, but not in PACAP (−/−) mice. PACAP may enhance lactate production and secretion in astrocytes during the acquisition and recall of fear memories.

SARS-CoV-2 infection has a wide spectrum of clinical manifestations secondary to the impairment of different organs, including kidney. Rhabdomyolysis is produced by disintegration of striated muscle and the liberation of its contents to the extracellular fluid and bloodstream. This may produce hydro electrolytic disorders and acute kidney injury. We report a 35-year-old female with a history of SARS-CoV-2 infection who was hospitalized because of respiratory failure and developed renal failure. The etiologic study showed elevated total creatine kinase levels and a magnetic resonance imaging confirmed rhabdomyolysis. The patient required supportive treatment with vasoactive drugs, mechanic ventilation and kidney replacement therapy. She had a favorable evolution with resolution of respiratory failure and improvement of kidney function.

Type 2 diabetes mellitus (T2DM) is one of the most common lifestyle-related diseases (metabolic disorders) due to hyperphagia and/or hypokinesia. Hyperglycemia is the most well-known symptom occurring in T2DM patients. Insulin resistance is also one of the most important symptoms, however, it is still unclear how insulin resistance develops in T2DM. Detailed understanding of the pathogenesis primarily causing insulin resistance is essential for developing new therapies for T2DM. Insulin receptors are located at the plasma membrane of the insulin-targeted cells such as myocytes, adipocytes, etc., and insulin binds to the extracellular site of its receptor facing the interstitial fluid. Thus, changes in interstitial fluid microenvironments, specially pH, affect the insulin-binding affinity to its receptor. The most well-known clinical condition regarding pH is systemic acidosis (arterial blood pH

The production of 51Cr-labelled ethylenediaminetetraacetic acid (51Cr-EDTA), a validated and widely used radio-isotopic tracer for glomerular filtration rate (GFR) measurement in Europe, was recently halted by the manufacturer. Technetium-99m-diethylenetriaminepentaacetic acid (99mTc-DTPA) clearance has so far mostly been restricted to assessment of separate renal function by scintigraphy, but scarcely used and validated for GFR measurement. We compared the performances of 51Cr-EDTA and 99mTc-DTPA for GFR and extracellular fluid measurement. In a multi-centre prospective study, 51Cr-EDTA and 99mTc-DTPA were simultaneously injected into 88 patients, and their urinary and plasma clearances, as well as their volumes of distribution, were measured during seven 30-min periods after a 90-min equilibrium time. Mean age was 52.2 ± 14.5 years, 59% were men. Urinary clearances of 51Cr-EDTA and 99mTc-DTPA were 64.1 ± 27.6 and 66.1 ± 28.0 mL/min, respectively, with a mean bias of 2.00 ± 2.25 mL/min, an accuracy within 10% of 95% [95% CI 91–99], and a coefficient of determination (R2) of 0.994. Plasma clearances of 51Cr-EDTA and 99mTc-DTPA were 66.1 ± 25.8 and 68.1 ± 26.6 mL/min, respectively, with a mean bias of 1.96 ± 3.32 mL/min, an accuracy within 10% of 91% [95% CI 85–97] and a R2 of 0.985. Distribution volumes were 17.3 ± 4.6 L for 51Cr-EDTA and 16.6 ± 4.6 L for 99mTc-DTPA (R2 0.930). The accuracy and precision of 99mTc-DTPA clearance, compared to 51Cr-EDTA clearance, was excellent for both urinary and plasma clearance methods, despite an approximate 2 mL/min overestimation, showing that the tracer is a reliable alternative to 51Cr-EDTA for GFR measurement.

The development of high blood pressure is influenced by genetic and environmental factors, with high salt intake being a known environmental contributor. Humans display a spectrum of sodium-sensitivity, with some individuals displaying a significant blood pressure rise in response to increased sodium intake while others experience almost no change. These differences are, in part, attributable to genetic variation in pathways involved in sodium handling and excretion. ENaC (epithelial sodium channel) is one of the key transporters responsible for the reabsorption of sodium in the distal nephron. This channel has an important role in the regulation of extracellular fluid volume and consequently blood pressure. Herein, we review the role of ENaC in the development of salt-sensitive hypertension, and present mechanistic insights into the regulation of ENaC activity and how it may accelerate sodium-induced damage and dysfunction. We discuss the traditional role of ENaC in renal sodium reabsorption and review work addressing ENaC expression and function in the brain, vasculature, and immune cells, and how this has expanded the implications for its role in the initiation and progression of salt-sensitive hypertension.

During the evolution of skeletons, terrestrial vertebrates acquired strong bones made of calcium-phosphate. By keeping the extracellular fluid in a supersaturated condition regarding calcium and phosphate ions, they created the bone when and where they wanted simply by providing a cue for precipitation. To secure this strategy, they acquired a novel endocrine system to strictly control the extracellular phosphate concentration. In response to phosphate intake, fibroblast growth factor-23 (FGF23) is secreted from the bone and acts on the kidney through binding to its receptor Klotho to increase urinary phosphate excretion, thereby maintaining phosphate homeostasis. The FGF23-Klotho endocrine system, when disrupted in mice, results in hyperphosphatemia and vascular calcification. Besides, mice lacking Klotho or FGF23 suffer from complex aging-like phenotypes, which are alleviated by placing them on a low- phosphate diet, indicating that phosphate is primarily responsible for the accelerated aging. Phosphate acquires the ability to induce cell damage and inflammation when precipitated with calcium. In the blood, calcium-phosphate crystals are adsorbed by serum protein fetuin-A and prevented from growing into large precipitates. Consequently, nanoparticles that comprised calcium-phosphate crystals and fetuin-A, termed calciprotein particles (CPPs), are generated and dispersed as colloids. CPPs increase in the blood with an increase in serum phosphate and age. Circulating CPP levels correlate positively with vascular stiffness and chronic non-infectious inflammation, raising the possibility that CPPs may be an endogenous pro-aging factor. Terrestrial vertebrates with the bone made of calcium- phosphate may be destined to age due to calcium-phosphate in the blood.

Aim The study aim was to compare the kinetics of the potassium analogue, 82 Rb, between spleen, liver and kidney. Methods Patients had myocardial stress/rest perfusion imaging using adenosine (n=45) or regadenoson (n=33) for stressing. Hepatic arterial (HAP), splenic (SP) and renal (RP) perfusions were measured from first-pass, and blood 82 Rb clearances (Ki) from Gjedde-Patlak-Rutland graphical analysis of data between 1 and 2 min post-injection, using regions of interest over left ventricular cavity or abdominal aorta to monitor arterial concentration. Tissue 82 Rb extraction efficiency (E) was calculated as [Ki/perfusion]*100. Tissue extracellular fluid volume (ECV) was derived from the GPR plot intercept. Results SP (24%) and RP (23%) increased after regadenoson but decreased (-41% and -19%) after adenosine. HAP increased after adenosine (91%) and regadenoson (68%). Resting E was high in kidney (69%) and low in spleen (26%). After adenosine, it increased to 91% in kidney and 49% in spleen. Assuming an arterial contribution of 25% to hepatic blood flow, resting E in liver was estimated as 23%. Relationships between Ki and perfusion in spleen and kidney were consistent with the Crone-Renkin equation (Ki = [1 - A.e-B/perfusion ]*perfusion), with respective values of A of 0.95 and 0.94 and B of 31 and 186 ml/min/100 ml. Splenic ECV decreased following adenosine from 62 to 39 ml/100ml and showed a logarithmic correlation with SP. Conclusion Kidney, spleen and liver display contrasting tissue kinetics. E is high in kidney and low in spleen and liver. Spleen is erectile, collapsing when perfusion decreases.

Introduction: Intra-dialytic hypotension (IDH) remains the most common complication with outpatient hemodialysis (HD) sessions. As fluid is removed during HD, there is contraction of the extracellular volume (ECW). We wished to determine whether the fall in ECW was associated with a fall in systolic blood pressure (SBP). Methods: We retrospectively reviewed the records of adult dialysis outpatients attending for their midweek sessions who had corresponding pre- and post-HD bioimpedance measurements of ECW. Result: We reviewed 736 patients, median age 67 (54–76) years, 62.8% male, 45.7% diabetic with a median dialysis vintage of 24.4 (9.2–56.8) months. The percentage fall in ECW (ECW%) was associated with post-dialysis systolic blood pressure (SBP) ( r = −0.14, p 20 mmHg had a greater fall in ECW% compared to patients with stable SBP 7.6 (4.6–10.1) vs 6.0 (4.0–8.5), p Conclusion: We observed an association between the reduction in ECW and SBP with dialysis. Our results would advocate monitoring ECW changes during dialysis and developing biofeedback devices to control ultrafiltration and dialysate sodium to reduce the risk of IDH.

NEW FINDINGS What is the central question of this study? What are the mechanisms by which equine sweat glands transport sodium, potassium and water into sweat? What is the main finding and its importance? The flux of sodium into sweat does not have an active transport component, the flux of potassium into sweat is partially dependent on an active transport mechanism, and there is no evidence for paracellular transport. ABSTRACT In two series of experiments, this study used radioactive sodium (Na+ ) and potassium (K+ ) to trace the net flux, and calculate the unidirectional fluxes, of these ions from extracellular fluid into sweat of horses during exercise and recovery. The effect of an oral electrolyte supplement (PNW) on the sweating responses and ion fluxes was also examined. Compared to 8 litres of water (controls), provision of 8 litres of PNW resulted in significantly increased sweating duration (P

BACKGROUND: Visualization of diffuse myocardial fibrosis is challenging and mainly relies on histology. Cardiac magnetic resonance (CMR), which uses extracellular contrast agents, is a rapidly developing technique for measuring the extracellular volume (ECV). The objective of this study was to evaluate the feasibility of the synthetic myocardial ECV fraction based on 3.0 T CMR compared with the conventional ECV fraction. METHODS: This study was approved by the local animal care and ethics committee. Fifteen beagle models with diffuse myocardial fibrosis, including 12 experimental and three control subjects, were generated by injecting doxorubicin 30 mg/m(2) intravenously every three weeks for 24 weeks. Short-axis (SAX) and 4-chamber long-axis (LAX) T1 maps were acquired for both groups. The association between hematocrit (Hct) and native T1(blood) was derived from 9 non-contrast CMR T1 maps of 3 control beagles using regression analysis. Synthetic ECV was then calculated using the synthetic Hct and compared with conventional ECV at baseline and the 16(th) and 24(th) week after doxorubicin administration. The collagen volume fraction (CVF) value was measured on digital biopsy samples. Bland-Altman plots were used to analyze the agreement between conventional and synthetic ECV. Correlation analyses were performed to explore the association among conventional ECV, synthetic ECV, CVF, and left ventricular ejection fraction (LVEF). RESULTS: The regression model synthetic Hct = 816.46*R1(blood) − 0.01 (R(2)=0.617; P=0.012) was used to predict the Hct from native T1(blood) values. The conventional and synthetic ECV fractions of experimental animals at the 16(th) and 24(th) week after modeling were significantly higher than those measured at the baseline (31.4%±2.2% and 36.3%±2.1% vs. 22.9%±1.7%; 29.9%±2.4% and 36.1%±2.6% vs. 22.0%±2.4%; all with P

BACKGROUND & AIMS Obesity is associated with higher extracellular fluid (ECF) compared to intracellular fluid (ICF) volume and this dysregulation is associated with hypertension and abdominal obesity, associated with metabolic syndrome. As sodium is predominantly an extracellular cation, a higher ECF/ICF ratio will lower serum sodium concentration. The aim of the study was to see whether weight loss, due to dieting and bariatric surgery, had any impact on serum sodium concentrations in patients with severe obesity. METHODS Patients with a BMI ≥35 kg/m2 admitted for bariatric surgery at Innlandet Hospital Trust, Norway during 2012-14 were included in the study (n = 119). Clinical data and blood samples were recorded at inclusion, after mean six months of dieting, as well as six and 12 months after bariatric surgery. RESULTS At inclusion, mean serum sodium was in the lower normal range, 138.3 (SD 2.4) mmol/L, but increased to 141.8 (SD 1.9) mmol/L after weight loss. The increase was significantly correlated to total weight loss (rho: 0.29, p = 0.007). Twelve months after surgery, serum sodium was significantly higher in patients with a normal BMI (

Cardiologists and emergency-wards physicians are used to check natriuretic peptides serum level, mainly B-type natriuretic peptide and N-terminal pro-Brain natriuretic peptide for acute cardiac failure diagnosis. Due to their accumulation in chronic kidney disease and their elimination by dialysis, natriuretic peptides sampling remains debatable in chronic kidney disease patients. In dialysis patients, high natriuretic peptides values are associated with mortality, left ventricular hypertrophy and cardiac failure. However, a single value cannot provide a reliable diagnosis. Our clinical practice is as follows: First, we prefer B-type natriuretic peptide to N-terminal pro-Brain natriuretic peptide because of its shorter half-life, with less impact of renal function and dialysis, making its interpretation easier in case of advanced chronic kidney disease or in dialysis patients; second, we define a reference value of B-type natriuretic peptide at dry weight from serial measurements; third, the B-type natriuretic peptide changes are interpreted according to extracellular fluid and cardiac status, but also from the arteriovenous fistula blood flow. In stable dialysis patients, B-type natriuretic peptide is sampled monthly and weekly in unstable patients. We illustrate our experience using clinical cases of overhydration, new cardiac disease onset, hypovolemia and arteriovenous fistula with high blood flow. Longitudinal follow-up of B-type natriuretic peptide is an important advance in dialysis patients in order to detect and treat extracellular fluid variations and cardiac disease status early, both important factors associated with hard outcomes.

Following myocardial infarction, tissue undergoes pathophysiological changes involving inflammation and scar tissue formation. However, little is known about the pathophysiology and prognostic significance of any corresponding changes in remote myocardium. The aim of this study was to investigate the potential application of a combined constant infusion of 18F-FDG and Gd-DTPA to quantitate inflammation and extracellular volume (ECV) from 3 to 40 days after myocardial infarction. Eight canine subjects were imaged at multiple time points following induction of an MI with a 60-minute concurrent constant infusion of Gd-DTPA and 18F-FDG using a hybrid PET/MRI scanner. There was a significant increase in ECV in remote myocardium on day 14 post-MI (P = .034) and day 21 (P = .021) compared to the baseline. ECV was significantly elevated in the infarcted myocardium compared to remote myocardium at all time points post-MI (days 3, 7, 14, 21, and 40) (P < .001) while glucose uptake was also increased within the infarct on days 3, 7, 14, and 21 but not 40. The significant increase in ECV in remote tissue may be due to an ongoing inflammatory process in the early weeks post-infarct.

Background Overhydration is a predictor of mortality in hemodialysis (HD) patients. Bioimpedance spectroscopy (BIS) is used to determine the body composition. Extracellular Water/Total Body Water (ECW/TBW) ratio has been proposed to predict mortality. Methods Multicenter, prospective, observational, proof-of-concept study to estimate the impact of ECW/TBW in global and cardiovascular mortality and the relationship with cardiovascular biomarkers. The study included 60 patients (mean age, 71.8 ± 11.4 years; mean time on HD, 52.3 ± 30.8 months) with a median follow-up of 30.5 months (IQ range, 17.2–34 months). Results Post-dialysis ECW/TBW was directly associated with NT-proBNP and cTnT. During the study 28 patients died, most of them (43%) due to cardiovascular events. Compared to the survivors, these subjects had a higher post-dialysis ECW/TBW ratio (p = 0.006), while for cardiovascular mortality the only significant difference was a higher pre-dialysis ECW/TBW. The ability of post-dialysis ECW/TBW ratio to predict all-cause mortality had an area under the ROC curve (AUC) of 0.71 (CI 95%, 0.57–0.81; p = 0.002), with a cutoff point of 0.5023. For cardiovascular mortality the AUC was 0.66 (CI 95%, 0.52–0.77; p = 0.045), with a cutoff point of 0.4713. Conclusions The post-dialysis ECW/TBW ratio measured by BIS can be a predictor of all-cause and cardiovascular mortality.

Introduction: The Frequent Hemodialysis Network (FHN) Daily and Nocturnal trials aimed to compare the effects of hemodialysis (HD) given 6 versus 3 times per week. More frequent in-center HD significantly reduced left-ventricular mass (LVM), with more pronounced effects in patients with low urine volumes. In this study, we aimed to explore another potential effect modifier: the predialysis serum sodium (SNa) and related proxies of plasma tonicity. Methods: Using data from the FHN Daily and Nocturnal Trials, we compared the effects of frequent HD on LVM among patients stratified by SNa, dialysate-to-predialysis serum-sodium gradient (GNa), systolic and diastolic blood pressure, time-integrated sodium-adjusted fluid load (TIFL), and extracellular fluid volume estimated by bioelectrical impedance analysis. Results: In 197 enrolled subjects in the FHN Daily Trial, the treatment effect of frequent HD on ∆LVM was modified by SNa. When the FHN Daily Trial participants are divided into lower and higher predialysis SNa groups (less and greater than 138 mEq/L), the LVM reduction in the lower group was substantially higher (−28.0 [95% CI −40.5 to −15.4] g) than in the higher predialysis SNa group (−2.0 [95% CI −15.5 to 11.5] g). Accounting for GNa, TIFL also showed more pronounced effects among patients with higher GNa or higher TIFL. Results in the Nocturnal Trial were similar in direction and magnitude but did not reach statistical significance. Discussion/Conclusion: In the FHN Daily Trial, the favorable effects of frequent HD on left-ventricular hypertrophy were more pronounced among patients with lower predialysis SNa and higher GNa and TIFL. Whether these metrics can be used to identify patients most likely to benefit from frequent HD or other dialytic or nondialytic interventions remains to be determined. Prospective, adequately powered studies studying the effect of GNa reduction on mortality and hospitalization are needed.

The pathological significance of amyloid-β1-42 (Aβ1-42) dynamics is poorly understood in the brain extracellular compartment. Here we test which of the concentration or the retention is critical for Aβ1-42 toxicity after injection of equal dose into dentate granule cell layer of freely moving rats. The toxicity of Aβ1-42 (25 µM) was compared between injections at the rate of 0.25 µL/min for 4 min (fast injection) and 0.025 µL/min for 40 min (slow injection). Dentate gyrus long-term potentiation (LTP) was affected 1 and 2 h after the fast injection, but not 4 h. In contrast, LTP was affected even 72 h after the slow injection. Aβ1-42 staining 5 min after finish of the slow injection was more intense in the dentate granule cell layer than of the fast injection. The present study indicates that the retention of Aβ1-42 in the extracellular fluid is correlated with neuronal Aβ1-42 uptake and plays a key role in Aβ1-42 neurotoxicity. In the extracellular fluid of the dentate gyrus, the retention period of Aβ1-42 is much more critical for Aβ1-42 toxicity than Aβ1-42 concentration. It is likely that Aβ1-42 toxicity is accelerated by the disturbance of Aβ1-42 metabolism in the dentate gyrus.

The association between extracellular volume (ECV) measured by computed tomography angiography (CTA) and clinical outcomes was evaluated in low-flow low-gradient (LFLG) aortic stenosis (AS) patients undergoing transcatheter aortic valve replacement (TAVR).Patients with LFLG AS comprise a high-risk group with respect to clinical outcomes. Although ECV, a marker of myocardial fibrosis, is traditionally measured with cardiac magnetic resonance, it can also be measured using cardiac CTA. The authors hypothesized that in LFLG AS, increased ECV may be associated with adverse clinical outcomes.In 150 LFLG patients with AS who underwent TAVR, ECV was quantified using pre-TAVR CTA. Echocardiographic and clinical information including all-cause death and heart failure rehospitalization (HFH) was obtained from electronic medical records. A Cox proportional hazards model was used to evaluate the association between ECV and death+HFH.During a median follow-up of 13.9 months (range 0.07 to 28.9 months), there were 31 death+HFH events (21%). Patients who experienced death+HFH had a greater median Society of Thoracic Surgery score (9.9 vs. 4.7; p 0.01), lower left ventricular ejection fraction (42.3 ± 20.2% vs. 52.7 ± 17.2%; p 0.01), lower mean transvalvular gradient (24.9 ± 8.9 mm Hg vs. 28.1 ± 7.3 mm Hg; p = 0.04) and increased mean ECV (35.5 ± 9.6% vs. 29.9 ± 8.2%; p 0.01) compared with patients who did not experience death+HFH. In a multivariable Cox proportional hazards model, increase in ECV was associated with increase in death+HFH, (hazard ratio per 1% increase: 1.04, 95% confidence interval: 1.01 to 1.09; p 0.01).In patients with LFLG AS, CTA measured increase in ECV is associated with increased risk of adverse clinical outcomes post-TAVR and may thus serve as a useful noninvasive marker for prognostication.

Calcium (Ca) is one of the most important mineral components of food, which is used to build and maintain the skeletal structure of the body. Calcium is the most important mineral in the body. About 99% of the body's calcium is found in bone and teeth, along with phosphorus and the rest in soft tissue and extracellular fluid. Calcium is involved in the human body for activities such as bone and tooth building, blood clotting, muscle contraction, nerve conduction, and cell metabolism. Calcium deficiency in children leads to physical and mental developmental disorders and the development of osteoporosis called Rashitisme. This condition causes abnormal bones, large joints, and difficulty moving. In adults, calcium deficiency causes osteomalacia, which results in decreased calcium density in the bones, resulting in hollow and brittle bones. Calcium deficiency is often associated with vitamin D deficiency, which leads to problems with bone mineralization and severe muscle cramps. The aim of this study was that calcium plays an important role in the human body for activities such as bone and tooth building, blood coagulation, muscle contraction, nerve conduction, and cell metabolism. The results of this study showed that calcium is the cause of bone strength. There should be enough calcium in the diet of children before adulthood so that the bones are properly compacted and adults do not develop osteoporosis. There is the research method in this article is in the style of a library and a new scientific barrier has been written and the importance of the role of calcium in the body and the effects of its deficiency on the growth and development of children have been studied.

The authors aimed to compare the effects of creatine (Cr) supplementation combined with resistance training on skeletal muscle mass (SMM), total body water, intracellular water (ICW), and extracellular water (ECW) in resistance-trained men as well as to determine whether the SMM/ICW ratio changes in response to the use of this ergogenic aid. Twenty-seven resistance-trained men received either Cr (n = 14) or placebo (n = 13) over 8 weeks. During the same period, subjects performed two split resistance training routines four times per week. SMM was estimated from appendicular lean soft tissue assessed by dual-energy X-ray absorptiometry. Total body water, ICW, and ECW were determined by spectral bioelectrical impedance. Both groups showed improvements (p p p > .05), whereas the SMM/ECW ratio decreased only in the Cr group (p p r = .71). The authors’ results suggest that the increase in muscle mass induced by Cr combined with resistance training occurs without alteration of the ratio of ICW to SMM in resistance-trained men.

Background Tolvaptan has been shown to improve congestion in heart failure patients. The purpose of this study was to evaluate the pharmacology and clinical efficacy of combined tolvaptan and furosemide therapy. Methods This study included 40 patients with systemic volume overload who were hospitalized for heart failure. Patients who showed no improvement in the condition after receiving 20 mg intravenous furosemide were included and were randomly selected to receive tolvaptan as an add-on to furosemide or to receive an increased dose of furosemide. We evaluated the bioelectrical impedance analyzer parameters, the parameters of the inferior vena cava using echocardiography, vital signs, body weight, urine output, and laboratory data for 5 days. Results In the changes from baseline between intracellular water volume (ICW) and extracellular water volume (ECW) after additional use of tolvaptan or furosemide from Day 1 to Day 5, there were no significant differences observed between ICW and ECW over 5 days in the tolvaptan + furosemide group, although differences were found in the furosemide group from Day 2 onward. Changes in the respiratory collapse of inferior vena cava increased significantly, and systolic blood pressure decreased significantly only in the furosemide group. Conclusions The present study clearly demonstrates that combined therapy with tolvaptan and furosemide removed excess ICW and ECW to an equal extent, while furosemide alone primarily removed ECW, including intravascular water.

Extracellular fluid (ECF) potassium concentration ([K+]) is maintained by adaptations of kidney and skeletal muscle, responses heretofore studied separately. We aimed to determine how these organ systems work in concert to preserve ECF [K+] in male C57BL/6J mice fed a K+-deficient diet (0K) versus 1% K+ diet (1K) for 10 days ( n = 5–6/group). During 0K feeding, plasma [K+] fell from 4.5 to 2 mM; hindlimb muscle (gastrocnemius and soleus) lost 28 mM K+ (from 115 ± 2 to 87 ± 2 mM) and gained 27 mM Na+ (from 27 ± 0.4 to 54 ± 2 mM). Doubling of muscle tissue [Na+] was not associated with inflammation, cytokine production or hypertension as reported by others. Muscle transporter adaptations in 0K- versus 1K-fed mice, assessed by immunoblot, included decreased sodium pump α2-β2 subunits, decreased K+-Cl− cotransporter isoform 3, and increased phosphorylated (p) Na+,K+,2Cl− cotransporter isoform 1 (NKCC1p), Ste20/SPS-1-related proline-alanine rich kinase (SPAKp), and oxidative stress-responsive kinase 1 (OSR1p) consistent with intracellular fluid (ICF) K+ loss and Na+ gain. Renal transporters’ adaptations, effecting a 98% reduction in K+ excretion, included two- to threefold increased phosphorylated Na+-Cl− cotransporter (NCCp), SPAKp, and OSR1p abundance, limiting Na+ delivery to epithelial Na+ channels where Na+ reabsorption drives K+ secretion; and renal K sensor Kir 4.1 abundance fell 25%. Mass balance estimations indicate that over 10 days of 0K feeding, mice lose ~48 μmol K+ into the urine and muscle shifts ~47 μmol K+ from ICF to ECF, illustrating the importance of the concerted responses during K+ deficiency.

Purpose of review Accumulating evidence supports the important contribution of volume-related metrics to morbidity and mortality in patients receiving chronic haemodialysis. The purpose of this review is to summarize recent advances in the understanding and management of volume status in this high-risk group. Recent findings Delivery of optimal volume management involves three key components: accurate estimation of volume status, correction of extracellular fluid overload and prevention of intradialytic instability. The lack of a gold standard for assessing volume status makes accurate estimation difficult to achieve; clinical examination has insufficient sensitivity and specificity, while tools to assist in the objective measurement of extracellular fluid volume require further validation. Hypervolemia is common in patients on chronic haemodialysis and substantially increases the risk of morbidity and mortality. Rapid correction of hypervolemia should be avoided due to the risk of precipitating intradialytic hypotension and hypoperfusion of vital end-organs, including the heart, brain, liver, gut and kidneys. Evidence-based interventions to aid in normalizing extracellular fluid volume are urgently needed; several targeted strategies are currently being evaluated. Many centres have successfully implemented local protocols and programmes to enhance volume management. Summary Achieving normal volume status is a fundamental goal of haemodialysis. Novel methods of assessing and restoring extracellular fluid volume while maintaining intradialytic stability are currently undergoing evaluation. Implementation of volume-related strategies into clinical practice is feasible and may improve patient outcome.

To investigate whether cardiovascular magnetic resonance (CMR) T1 mapping and strain parameters can detect early histological and functional myocardial changes in idiopathic inflammatory myopathy (IIM) with negative late gadolinium enhancement (LGE) and preserved ejection fraction. Thirty consecutive patients with IIM (41.5 ± 15.4 years, 24 females) who did not have LGE or reduced left ventricular ejection fraction (LVEF) and 30 age- and gender-matched healthy controls (40.6 ± 14.2 years, 20 females) were recruited. Patients with IIM were further classified into two subgroups according to high-sensitivity cardiac troponin I (hs-cTnI) values: elevated hs-cTnI subgroup (n = 10) and normal hs-cTnI subgroup (n = 20). Myocardial native T1 values, extracellular volume (ECV) fractions, and strain parameters were analyzed in patients with IIM and healthy controls. Compared with healthy controls, patients with IIM had significantly prolonged native T1 values and increased ECV in each LV segment (p < 0.05). In further subgroup analysis, LV mid-slice native T1 values had the most power to discriminate between patients with elevated hs-cTnI and healthy controls (area under the curve = 0.92). There was no significant difference of global LV strain or strain rates between IIM patients and controls. Diffuse interstitial fibrosis can be detected by CMR T1 mapping in patients with IIM who do not have LGE or reduced LVEF or elevated hs-cTnI, and it may be a promising method for screening subclinical cardiac involvement in IIM. • Myocardial abnormality in IIM is often subclinical and leads to poor prognosis. • Conventional CMR parameters have limitations in early detection of cardiac function and tissue changes. • CMR T1 mapping techniques and myocardial strain analysis have the potential to provide detailed information on cardiac histology and function.

It is not yet known whether continuous glucose monitoring (CGM) abnormalities persist in young children with CF. We evaluated longitudinal CGM results for children with CF 10 years of age. We performed 3-day CGM at baseline, 12 months, and 24 months on 11 CF children (1 female) initially aged mean (SD) 3.8 (2.5) years. CGM analysis included (i) mean sensor glucose (SG), (ii) standard deviation (SD) for SG, (iii) peak SG and (iv)% time spent above a threshold of 7.8 mmol/L. Only three (3/11, 27%) had normal CGM at all time-points. Nearly three quarters of the participants (8/11, 73%) spent more than 4.5 percent time 7.8 mmol/L at one time-point, five of whom had an elevated percent time on a subsequent test. Young children with CF have glucose abnormalities detected by CGM that fluctuate over time.