Early predictive value of lipocalin-type prostaglandin D synthase for 28-day mortality in cardiac arrest patients: study protocol for a prospective study.

INTRODUCTION: Public training in cardiopulmonary resuscitation and treatment in emergency and intensive care unit have made tremendous progress. However, cardiac arrest remains a major health burden worldwide, with brain damage being a significant contributor to disability and mortality. Lipocalin-type prostaglandin D synthase (L-PGDS), which is mainly localised in the central nervous system, has been previously shown to inhibit postischemia neuronal apoptosis. Therefore, we aim to observe whether serum L-PGDS can serve as a potential biomarker and explore its role in determining the severity and prognosis of patients who have achieved restoration of spontaneous circulation (ROSC). METHODS AND ANALYSIS: This is a prospective observational study. The participants (n = 60) who achieve ROSC will be distributed into two groups (non-survivor and survivor) based on 28-day survival. Healthy volunteers (n = 30) will be enrolled as controls. Each individual's relevant information will be extracted from Electronic Medical Record System in Xinhua Hospital, including demographic characteristics, clinical data, laboratory findings and so on. On days 1, 3 and 7 after ROSC, blood samples will be drawn and batch tested on the level of serum neuron-specific enolase, soluble protein 100ß, L-PGDS, procalcitonin, tumour necrosis factor-alpha and interleukin-6. The cerebral performance category score was assessed on the 28th day after ROSC. ETHICS AND DISSEMINATION: This study was performed with the approval of the Clinical Ethical Committee of Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Approval No. XHEC-C-2023-130-1). The results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2300078564).

Noninvasive Markers of Inflammation and Protein Loss Augment Diagnosis of Pediatric Celiac Disease.

INTRODUCTION: Circulating tissue transglutaminase immunoglobulin A concentration is a sensitive and specific indicator of celiac disease, but discrepancies between serologic and histologic findings occur. We hypothesized that fecal markers of inflammation and protein loss would be greater in patients with untreated celiac disease than in healthy controls. Our study aims to evaluate multiple fecal and plasma markers in celiac disease and correlate these findings with serologic and histologic findings as noninvasive means of evaluating disease activity. METHODS: Participants with positive celiac serologies and controls with negative celiac serologies were prospectively enrolled before upper endoscopy. Blood, stool, and duodenal biopsies were collected. Concentrations of fecal lipocalin-2, calprotectin, and alpha-1-antitrypsin and plasma lipocalin-2 were determined. Biopsies underwent modified Marsh scoring. Significance was tested between cases and controls, modified Marsh score and tissue transglutaminase immunoglobulin A concentration. RESULTS: Lipocalin-2 was significantly elevated in the stool ( P = 0.006) but not the plasma of participants with positive celiac serologies. There was no significant difference in fecal calprotectin or alpha-1 antitrypsin between participants with positive celiac serologies and controls. Fecal alpha-1 antitrypsin >100 mg/dL was specific, but not sensitive for biopsy-proven celiac disease. DISCUSSION: Lipocalin-2 is elevated in the stool but not the plasma of patients with celiac disease suggesting a role of local inflammatory response. Calprotectin was not a useful marker in the diagnosis of celiac disease. While random fecal alpha-1 antitrypsin was not significantly elevated in cases compared with controls, an elevation of greater than 100 mg/dL was 90% specific for biopsy-proven celiac disease.

Aumento de la lipocalina orosomucoide-1 (ORM1) en sujetos con hiperaldosteronismo primario / Increase of lipocalin ORM1 in primary aldosteronism

El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.

Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.

Lipocalin 10 as a New Prognostic Biomarker in Sepsis-Induced Myocardial Dysfunction and Mortality: A Pilot Study.

INTRODUCTION: Sepsis-induced myocardial dysfunction (SIMD) is the most common complications of sepsis and septic shock with extremely high incidence and mortality. Lipocalin 10 (Lcn10) has recently been identified as a potential biomarker for heart failure, yet its relation to sepsis has not been investigated. The purpose of this study was to explore whether circulating Lcn10 could be used as a prognostic tool in patients with SIMD. METHODS: In this single-center observational pilot study, seventy-five sepsis patients were enrolled after sepsis diagnosis or ICU admission (45.3% female, median age 60 years), and 35 patients (46.7%) developed myocardial dysfunction. Serum Lcn10 levels of septic patients were measured using the enzyme-linked immunosorbent assay (ELISA) at the time of admission. Other biomarkers of cardiac function and Lcn10 concentration were compared between SIMD and non-SIMD groups. RESULTS: We observed that the median Lcn10 levels were 2.780 ng/mL in patients with SIMD and 2.075 ng/mL in patients without SIMD (P < 0.05). The area under the receiver operating characteristic (ROC) curve for the diagnosis of SIMD was 0.797 (P < 0.05). In addition, elevated serum Lcn10 levels at the time of admission were positively associated with 28-day mortality in septic patients. CONCLUSIONS: Our study indicates that circulating Lcn10 levels may serve as a novel biomarker for the diagnosis and prognosis of myocardial dysfunction induced by sepsis. An additional large multicenter study may be warranted to confirm the findings of this study.

Prolonged Changes in Hepatic Mitochondrial Activity and Insulin Sensitivity by High Fructose Intake in Adolescent Rats.

Persistence of damage induced by unhealthy diets during youth has been little addressed. Therefore, we investigated the impact of a short-term fructose-rich diet on liver metabolic activity in adolescent rats and the putative persistence of alterations after removing fructose from the diet. Adolescent rats were fed a fructose-rich diet for three weeks and then switched to a control diet for further three weeks. Body composition and energy balance were not affected by fructose-rich diet, while increased body lipids and lipid gain were found after the rescue period. Switching to a control diet reversed the upregulation of plasma fructose, uric acid, lipocalin, and haptoglobin, while plasma triglycerides, alanine aminotransferase, lipopolysaccharide, and tumor necrosis factor alpha remained higher. Hepatic steatosis and ceramide were increased by fructose-rich diet, but reversed by returning to a control diet, while altered hepatic response to insulin persisted. Liver fatty acid synthase and stearoyl-CoA desaturase (SCD) activities were upregulated by fructose-rich diet, and SCD activity remained higher after returning to the control diet. Fructose-induced upregulation of complex II-driven mitochondrial respiration, peroxisome proliferator-activated receptor-gamma coactivator 1 alpha, and peroxisome proliferator activated receptor α also persisted after switching to control diet. In conclusion, our results show prolonged fructose-induced dysregulation of liver metabolic activity.

Beta-trace protein as a potential biomarker of residual renal function in patients undergoing peritoneal dialysis.

BACKGROUND: Residual renal function is closely linked to quality of life, morbidity and mortality in dialysis patients. Beta-trace protein (BTP), a low molecular weight protein, has been suggested as marker of residual renal function, in particular in patients on hemodialysis. We hypothesized that BTP also serves as a marker of residual renal function in pertioneal dialysis patients. METHODS: In this study 34 adult patients on peritoneal dialysis were included. BTP, creatinine, cystatin C and urea concentrations were analyzed simultaneously in serum and dialysate to calculate renal and peritoneal removal of the analytes. RESULTS: In peritoneal dialysis patients with residual diuresis, mean serum BTP was 8.16 mg/l (SD ± 4.75 mg/l). BTP correlated inversely with residual diuresis (rs = - 0.58, p < 0.001), residual creatinine clearance (ClCr) (rs = - 0.69, p < 0.001) and total urea clearance (Clurea) (rs = - 0.56, p < 0.001). Mean peritoneal removal of BTP was 3.36 L/week/1.73m2 (SD ± 1.38) and mean renal removal 15.14 L/week/1.73m2 (SD ± 12.65) demonstrating a significant renal contribution to the total removal. Finally, serum BTP inversely correlated with alterations in residual diuresis (r = - 0.41, p = 0.035) and renal creatinine clearance over time (r = - 0.79, p = p < 0.001). CONCLUSION: BTP measurement in the serum may be a simple tool to assess residual renal function in peritoneal dialysis patients.

Lipocalin 13 enhances insulin secretion but is dispensable for systemic metabolic control.

Members of the lipocalin protein family serve as biomarkers for kidney disease and acute phase inflammatory reactions, and are under preclinical development for the diagnosis and therapy of allergies. However, none of the lipocalin family members has made the step into clinical development, mostly due to their complex biological activity and the lack of in-depth mechanistic knowledge. Here, we show that the hepatokine lipocalin 13 (LCN13) triggers glucose-dependent insulin secretion and cell proliferation of primary mouse islets. However, inhibition of endogenous LCN13 expression in lean mice did not alter glucose and lipid homeostasis. Enhanced hepatic secretion of LCN13 in either diet-induced or genetic obesity led to no discernible impact on systemic glucose and lipid metabolism, neither in preventive nor therapeutic setting. Of note, loss or forced LCN13 hepatic secretion did not trigger any compensatory regulation of related lipocalin family members. Together, these data are in stark contrast to the suggested gluco-regulatory and therapeutic role of LCN13 in obesity, and imply complex regulatory steps in LCN13 biology at the organismic level mitigating its principal insulinotropic effects.

Long-Term Longitudinal Stability of Kidney Filtration Marker Measurements: Implications for Epidemiological Studies and Clinical Care.

BACKGROUND: Establishment and improvement of glomerular filtration rate estimating equations requires accurate and precise laboratory measurement procedures (MPs) for filtration markers. The Advanced Research and Diagnostic Laboratory (ARDL) at the University of Minnesota, which has served as the central laboratory for the Chronic Kidney Disease Epidemiology Collaboration since 2009, has implemented several quality assurance measures to monitor the accuracy and stability of filtration marker assays over time. METHODS: To assess longitudinal stability for filtration marker assays, a 40-sample calibration panel was created using pooled serum, divided into multiple frozen aliquots stored at -80 °C. ARDL monitored 4 markers-creatinine, cystatin C, beta-2-microglobulin (B2M) and beta-trace protein-measuring 15 calibration panel aliquots from 2009 to 2019. Initial target values were established using the mean of the first 3 measurements performed in 2009-10, and differences from target were monitored over time. New MPs for cystatin C and B2M were added in 2012, with target values established using the first measurement. RESULTS: The mean percentage difference from mean target values across time was <2% for all original MPs (-0.59% for creatinine; -0.94% for cystatin C; -0.82% for B2M; 1.24% for beta-trace protein). CONCLUSIONS: Close monitoring of filtration marker trends with a calibration panel at ARDL demonstrates remarkable long-term stability of the MPs. Routine use of a calibration panel for both research studies and clinical care is recommended for filtration markers where longitudinal monitoring is important to detect analytical biases, which can mask or confound true clinical trends in patients.

Formulas Estimating Glomerular Filtration Rate in the Evaluation of Living Kidney Donor Candidates: Comparison of Different Formulas With Scintigraphy-Measured Glomerular Filtration Rate.

INTRODUCTION: Estimation of kidney function is crucial in the evaluation of living kidney donor candidates. Despite the multitude of glomerular filtration rate (GFR) formulas, no equation is universal, and none were validated in the population of kidney donors. Novel biomarkers, including beta trace protein (BTP) and cystatin C, are studied to help estimate GFR and improve the safe qualification of living kidney donors. AIM: This study compares the accuracy of different formulas that estimate GFR with reference scintigraphy-measured GFR in the population of living kidney donor candidates. MATERIAL AND METHODS: This study enrolled 30 healthy living kidney donor candidates. GFR was measured using the following 11 different formulas. For reference, GFR was assessed using 99m-Technetium-diethylenetriaminepentaacetic acid. RESULTS: The accuracy of estimation was generally low in all formulas. The strongest correlation between measured GFR (mGFR) and estimated GFR (eGFR) was achieved by the Nankivell formula (R = 0.47, P = .009); however, in the group of patients with a body mass index of >25 kg/m2, only the equations based on BTP had a statistically significant correlation with mGFR: White (R = 0.59; P = .016) and Poge (R = 0.53; P = .035). Bland-Altman plots revealed wide limits of agreement between eGFRs and mGFR in all groups of patients. CONCLUSION: In living kidney donor candidates, GFR estimation formulas should be chosen individually. White formula, which is based on BTP, may be a promising tool in estimating GFR in overweight potential living kidney donor candidates. More than 1 formula and personalized choice of GFR estimation method regarding the given patient should be performed in qualification of kidney donors.

Age appropriate reference intervals for eight kidney function and injury markers in infants, children and adolescents.

Objectives: The use of kidney function and injury markers for early detection of drug-related glomerular or tubular kidney injury in infants, children and adolescents requires age-specific data on reference intervals in a pediatric healthy population. This study characterizes serum values for eight kidney function and injury markers in healthy infants, children and adolescents. Methods: A single center prospective observational study was conducted between December 2018 and June 2019. Serum samples from 142 healthy infants, children and adolescents aged between 0 and ≤15 years were collected. Statistical analyses for eight markers (albumin (ALB), ß2-microglobulin (B2M), ß-trace protein (BTP), creatinine (SCR), cystatin C (CYSC), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), uromodulin (URO)) were performed to obtain reference intervals and associations with age, sex and weight were investigated (Pearson correlation, linear and piecewise regression). Results: ALB and SCR increased with age (p<0.01), whereas B2M, BTP and KIM-1 values decreased with advancing age (p<0.05) in this healthy pediatric study population. CYSC showed dependency on sex (lower concentration in females) and decreased with age until reaching approximately 1.8 years; thereafter an increase with age was seen. NGAL and URO did not show any age-dependency. Conclusions: This study provides age appropriate reference intervals for key serum kidney function and injury markers determined in healthy infants, children and adolescents. Such reference intervals facilitate the interpretation of changes in kidney function and injury markers in daily practice, and allow early detection of glomerular and tubular injury in infancy, childhood and adolescence.

Predictive value of cystatin C and neutrophil gelatinase-associated lipocalin in contrast-induced nephropathy: A meta-analysis.

BACKGROUND: There are still limited studies comprehensively examining the diagnostic performance of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C in contrast-induced nephropathy (CIN). The study aimed to investigate and compare the predictive value of NGAL and cystatin C in the early diagnosis of CIN. METHODS AND MATERIALS: We searched the PubMed, EMBASE and Cochrane Library databases until November 10, 2019. The methodological quality of the included studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Bivariate modeling and hierarchical summary receiver operating characteristic (HSROC) modeling were performed to summarize and compare the diagnostic performance of blood/urine NGAL and serum cystatin C in CIN. Subgroup and meta-regression analyses were performed according to the study and patient characteristics. RESULTS: Thirty-seven studies from thirty-one original studies were included (blood NGAL, 1840 patients in 9 studies; urine NGAL, 1701 patients in 10 studies; serum cystatin C, 5509 patients in 18 studies). Overall, serum cystatin C performed better than serum/urine NGAL (pooled DOR: 43 (95%CI: 12-152); AUROC: 0.93; λ: 3.79); serum and urine NGAL had a similar diagnostic performance (pooled DOR: 25 (95%CI: 6-108)/22(95%CI: 8-64); AUROC: 0.90/0.89; λ: 3.20/3.08). Meta-regression analysis indicated that the sources of heterogeneity might be CIN definition, assays, and nationalities. CONCLUSION: Both NGAL and cystatin C can serve as early diagnostic indicators of CIN, while cystatin C may perform better than NGAL.

High sPLA2-IIA level is associated with eicosanoid metabolism in patients with bacterial sepsis syndrome.

The aim of this study was to determine the association between secretory phospholipase A2 group IIA (sPLA2-IIA) and eicosanoid pathway metabolites in patients with bacterial sepsis syndrome (BSS). Levels of sPLA2-IIA, eicosanoids prostaglandin (PG)E2, PGD synthase were quantified in the sera from patients confirmed to have bacterial sepsis (BS; N = 45), bacterial severe sepsis/septic shock (BSS/SS; N = 35) and healthy subjects (N = 45). Cyclooxygenase (COX)-1 and COX-2 activities were analyzed from cell lysate. Serum levels of sPLA2-IIA, PGE2, and PGDS increased significantly in patients with BS and BSS/SS compared to healthy subjects (p<0.05). COX-2 activity was significantly increased in patients with BS compared to healthy subjects (p<0.05), but not COX-1 activity. Binary logistic regression analysis showed that sPLA2-IIA and PGE2 were independent factors predicting BSS severity. In conclusion, high level of sPLA2-IIA is associated with eicosanoid metabolism in patients with BSS.

Kidney-Detrimental Factors and Estimated Glomerular Filtration Rate in Preterm Newborns: The Role of Nutrition.

: Background: Kidney function in preterm newborns may be impaired by many factors. METHODS: 71 newborns with gestational age (GA) < 32 weeks were enrolled. Serum creatinine (sCr), cystatin C (CysC), beta-trace protein (BTP) and urea were measured at T0 (3rd day of life) and T36 (GA 36 weeks), and estimated glomerular filtration rate (eGFR) was calculated according to different formulas at T36. Pre-natal and post-natal kidney injury risk scores were calculated. RESULTS: Newborns with GA ≤ 28 weeks had higher sCr at T0, and lower sCr, BTP and higher urea levels at T36 (p = 0.007, p = 0.005 and p = 0.029, respectively). eGFR values were not different according to GA when calculated by the formulas using only CysC, but were higher in subjects with GA ≤ 28 weeks according to the other formulas. The post-natal score was positively correlated with eGFR according to sCr-based formulas, but the correlations did not persist when adjusted for urea levels and GA. CONCLUSIONS: CysC-based eGFR values are not influenced by GA. Post-natal score shows a direct correlation with eGFR according to sCr-based formulas, not persisting after adjustment for GA and urea levels, implying the importance of the nutritional status, since more premature subjects receive a more aggressive nutritional regimen, testified by higher urea levels.

Lipocalin-type prostaglandin D synthase levels are associated with the severity of pulmonary embolism.

Pulmonary thromboembolism (PTE) is an acute emergency with high mortality and morbidity rates. This study aimed to investigate the importance of Lipocalin-type prostaglandin D synthase (L-PGDS) in predicting mortality and prognosis in PTE. The study prospectively included 90 patients who were admitted to the emergency department and in whom PTE was confirmed by computed tomographic pulmonary angiography as well as 40 healthy volunteers with no disease. L-PGDS levels in the venous blood were measured and compared. Pulmonary embolism severity index (PESI) prognosis scores of all patients and 1-month mortality rate were calculated. There was a statistically significant difference between the L-PGDS levels of the patient and control groups (P = 0.024), and 1-month mortality of patients diagnosed with PTE was 20% (n = 18). Furthermore, the patients were divided into two groups: patients deceased within 1 month following the diagnosis and survivors. L-PGDS levels of the deceased patients were significantly higher than those of the survivors (P < 0.001). Age, systolic blood pressure, pulse, shock index, lactate, and PESI scores were significantly different between the survivors and deceased patients. The cut-off value for L-PGDS obtained using receiver operating characteristic (ROC) curve analysis for 1-month mortality was 815.26 ng/mL (sensitivity: 83.33%; specificity: 79.17%; area under the curve: 0.851; 95% confidence interval 0.760-0.917; P < 0.001). Based on this cut-off value, logistic regression analysis revealed that increased L-PGDS, together with PESI, was an independent indicator of 1-month mortality. L-PGDS is associated with short-term mortality in patients with PTE; therefore, it can be used to predict mortality risk in patients with PTE.

Concurrence of elevated FeNO and airway hyperresponsiveness in nonasthmatic adolescents.

OBJECTIVES: The aim of this study was to investigate airway responsiveness and eosinophil and neutrophil inflammatory markers in clinically confirmed nonasthmatic adolescents with elevated fractional exhaled nitric oxide (FeNO), a marker of type-2 inflammation in the airways. METHODOLOGY: A total of 959 subjects from a general population, aged 12 to 15 years, answered a standardised questionnaire and underwent FeNO measurements at a screening visit at school. Adolescents without asthma, who had elevated FeNO (FeNO100 > 15 ppb) (n = 19), and control subjects, with low FeNO (FeNO100 < 5 ppb) and without reported symptoms of asthma or allergy (n = 28), participated in a follow-up study where FeNO50 , airway responsiveness to methacholine (PD20 ), blood eosinophil counts, and serum neutrophil lipocalin (HNL) and myeloperoxidase (MPO) levels were measured. Questionnaire follow-ups were performed 4 and 16 years later. RESULTS: Airway responsiveness (PD20 : 6.94 [1.87, 11.39] vs 11.42 [6.33, 59.4] µmol; P < .05) and blood eosinophil counts (0.31 [0.20, 0.44] vs 0.13 [0.1, 0.22] 109 /L; P < .001) (geometric mean [95% CI]) were higher among cases than controls. A significant correlation between blood eosinophils and FeNO was found (rho = 0.41; P = .005). In contrast, serum HNL and MPO were lower in cases than controls (P < .05 both), and there was a negative correlation between HNL and FeNO (r = -0.31; P = .04). At both follow-ups, a higher proportion of subjects reported allergic symptoms compared with baseline (P = .02, P = .01). CONCLUSIONS: Elevated FeNO in nonasthmatic adolescents was associated with airway hyperresponsiveness, elevated blood eosinophil counts, and lower systemic activation of neutrophils.

Sex specificity of kidney markers to assess prognosis in cirrhotic patients with TIPS.

BACKGROUND & AIMS: Renal function assessed by creatinine is a key prognostic factor in cirrhotic patients. However, creatinine is influenced by several factors, rendering interpretation difficult in some situations. This is especially important in early stages of renal dysfunction where renal impairment might not be accompanied by an increase in creatinine. Other parameters, such as cystatin C (CysC) and beta-trace protein (BTP), have been evaluated to fill this gap. However, none of these studies have considered the role of the patient's sex. The present study analysed CysC and BTP to evaluate their prognostic value and differentiate them according to sex. PATIENTS AND METHODS: CysC and BTP were measured in 173 transjugular intrahepatic portosystemic shunt (TIPS)-patients from the NEPTUN-STUDY(NCT03628807) and analysed their relationship with mortality and sex. Propensity score for age, MELD, etiology and TIPS indication was used. RESULTS: Cystatin C and BTP showed excellent correlations with creatinine values at baseline and follow-up. CysC was an independent predictor of overall mortality (HR = 1.66(1.33-2.06)) with an AUC of 0.75 and identified a cut-off of 1.55 mg/L in the whole cohort. Interestingly, CysC was significantly lower in females, also after propensity score matching. In males, the only independent predictor was the creatinine level (HR = 1.54(1.25-1.58)), while in females CysC levels independently predicted mortality (HR = 3.17(1.34-7.52)). CONCLUSION: This study demonstrates for the first time that in TIPS-patients creatinine predicts mortality in males better than in females, whereas CysC is a better predictor of mortality in females. These results may influence future clinical decisions on therapeutic options for example, allocation for liver transplantation in TIPS-patients.

Novel Urinary Biomarkers for Acute Kidney Injury and Prediction of Clinical Outcomes After Pediatric Cardiac Surgery.

Acute kidney injury (AKI) is a serious complication of pediatric cardiac surgery, with high morbidity and mortality. We aimed to evaluate the perioperative risk factors for AKI, and the validity of novel diagnostic urinary biomarkers after pediatric cardiac surgery. We analyzed 103 consecutive pediatric patients (≤ 18 years old), who underwent cardiac surgery. AKI was defined by ≥ 50% increase in serum creatinine levels from baseline. Urinary liver-type fatty acid binding protein (L-FABP) and neutrophil gelatinase-associated lipocalin (NGAL) were measured postoperatively at the intensive care unit (ICU) admission, subsequently at 4, 12, and 24 h. Areas under the receiver-operating characteristic curves (AUC) were calculated at each assessment time. AKI had developed in 47 patients (45.6%) by the second postoperative day. Univentricular status, aortic cross-clamping time, and intraoperative fluid balance were independently associated with AKI (p = 0.02, 0.01 and 0.01, respectively). Urinary L-FABP and NGAL were significantly higher in the AKI group at each point (p < 0.05). The predictive abilities of both biomarkers (AUC = 0.78-0.90) at ICU admission and 4 h after were especially high. The patients with L-FABP greater than the cutoff value at ICU admission and 4 h after ICU admission had significantly longer intubation and hospitalization periods (p < 0.05). Those with elevated NGAL levels at admission, and 4 h and 24 h after ICU admission, had significantly longer intubation, ICU stay, and hospitalization (p < 0.05). L-FABP and NGAL can be useful biomarkers for detecting early AKI after pediatric cardiac surgery and predicting adverse clinical outcomes.

Evidence for shrunken pore syndrome in children.

The link between cystatin C and mortality independent of glomerular filtration rate (GFR) in adults has prompted the "Shrunken Pore Syndrome" (SPS) hypothesis, where high serum cystatin C with normal creatinine is explained by smaller glomerular pores, through which creatinine can pass freely, while the larger cystatin C, beta-trace protein (BTP) and pro-inflammatory molecules are retained. This study set out to apply the definition of SPS to children. In 294 children who underwent inulin clearance (Cin) test, serum creatinine, cystatin C and BTP were measured. For all three markers eGFRx was calculated using the full age spectrum equations. The ratio eGFRcys/eGFRcrea was plotted against the error of eGFRBTP(%) (i.e. eGFRBTP-Cin)/Cin*100%). Patients with and without SPS according to different cut-off points of eGFRcys/eGFRcrea and eGFRcys/Cin (i.e. ≤0.6,0.7,0.8) were compared in terms of eGFRx, Cin, error of eGFRx(%) and eGFRBTP/eGFRcrea-ratio. The ratio eGFRcys/eGFRcrea and error of eGFRBTP(%) were positively correlated. The prevalence of SPS by eGFRcys/eGFRcrea with a cut-off of 0.6 was 4.8%. Patients with SPS had a more negative error of eGFRcys(%) and eGFRBTP(%) and higher Cin regardless of the definition. Overestimation of eGFRcrea in patients with SPS was only present when using the eGFRcys/eGFRcrea rather than the eGFRcys/Cin definition. Cystatin C and BTP are related independent of creatinine, suggesting glomerular pore size as a common denominator. The prevalence of SPS in children is comparable to adults. For research in SPS, a definition based on eGFRcys/exogenous clearance study may be useful to study the effect of SPS on creatinine metabolism.

Serum human neutrophil lipocalin: An effective biomarker for diagnosing bacterial infections.

BACKGROUND: Human neutrophil lipocalin (HNL) is used as a novel biomarker for infections. However, only a few studies have focused on the usefulness of HNL. The purpose of this study was to evaluate the diagnostic efficiency of HNL for identifying bacterial infections and to compare HNL with procalcitonin (PCT) and C-reactive protein (CRP). METHODS: Hospital patients with acute infections of bacterial origin (n = 439), viral origin (n = 71), and healthy volunteers (n = 67) were included in the study. The infection status of each patient was verified using microbiological, serological, and PCR testing. Additionally, CRP, HNL, and PCT levels were measured by established methods. RESULTS: In distinguishing bacterial and viral infections, area under the curve (AUC) analysis showed that, with a value of 0.81 (95% CI, 0.76-0.86), HNL was superior to CRP at 0.73 (0.68-0.79) and PCT at 0.64 (0.58-0.70). Interestingly, the combination of HNL, PCT, and CRP improved the diagnostic potential significantly with an AUC of 0.86 (0.82-0.90, P < 0.05). Furthermore, when comparing different infection site subgroups with healthy patients, HNL levels were higher in all bacterial groups, albeit to widely varying degrees (P < 0.0001), and HNL reached a higher level in bloodstream and abdominal infections. CRP levels showed the same trend as HNL levels. PCT levels were significantly increased in bloodstream infections, abdominal infections, and in bacterial pneumonia (P < 0.0001), while no significant differences were found in soft tissue (P = 0.4378) or urinary tract infections (P = 0.423). There was no difference in HNL and CRP levels between patients with Gram-negative bacterial (GNB) or Gram-positive bacterial infections. However, compared with controls, PCT was only increased in GNB-infected patients. CONCLUSION: HNL detection can help diagnose patients with infectious diseases, and the diagnostic efficacy of HNL is not affected by the infected site or by pathogenic bacterial species. The combination of HNL, PCT, and CRP has a superior performance at identifying bacterial infections compared with traditional biomarkers.