scholarly journals The Role of Osteopontin as a Diagnostic and Prognostic Biomarker in Sepsis and Septic Shock

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 174 ◽  
Author(s):  
Luigi Mario Castello ◽  
Marco Baldrighi ◽  
Luca Molinari ◽  
Livia Salmi ◽  
Vincenzo Cantaluppi ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Extracellular Matrix Protein ◽  
Suspected Infection ◽  
Significant Difference ◽  
Life Threatening ◽  
Sepsis And Septic Shock

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host-response to infections. Osteopontin (OPN) is an extracellular matrix protein involved in the inflammatory response. Our aim was to evaluate the diagnostic and prognostic performance in sepsis of a single OPN determination in the Emergency Department (ED). We conducted a single-centre prospective observational study in an Italian ED where we enrolled 102 consecutive patients presenting with suspected infection and qSOFA ≥ 2. OPN plasma concentration was found to be an independent predictor of sepsis (OR = 1.020, 95% CI 1.002–1.039, P = 0.031) and the diagnostic receiver operating characteristic (ROC) curve resulted in an area under the curve (AUC) of 0.878. OPN levels were positively correlated to plasma creatinine (r = 0.401 with p = 0.0001), but this relation was not explained by the development of acute kidney injury (AKI), since no difference was found in OPN concentration between AKI and non-AKI patients. The analysis of 30-days mortality showed no significant difference in OPN levels between alive and dead patients (p = 0.482). In conclusion, a single determination of OPN concentration helped to identify patients with sepsis in the ED, but it was not able to predict poor prognosis in our cohort of patients.

scholarly journals Beta-Trace Protein as a Potential Marker of Acute Kidney Injury: A Pilot Study

2021 ◽  
pp. 1-11
Author(s):  
Katrien Leyssens ◽  
Niels Van Regenmortel ◽  
Ella Roelant ◽  
Khadija Guerti ◽  
Marie Madeleine Couttenye ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Roc Analysis ◽  
Area Under The Curve ◽  
Kidney Injury ◽  
Great Accuracy ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Potential Marker ◽  
Significant Difference ◽  
Neutrophil Gelatinase

<b><i>Introduction:</i></b> Acute kidney injury (AKI) is a frequent complication among patients in the intensive care unit (ICU). The limitations of serum Cr (sCr) in timely detecting AKI are well known. Beta-trace protein (BTP) is emerging as a novel endogenous glomerular filtration rate marker. The aim of this study was to explore the role of BTP as a marker of AKI. <b><i>Methods:</i></b> Patients admitted to the ICU undergoing surgery were included. BTP, sCr, Cystatin C (CysC), and neutrophil gelatinase-associated lipocalin (NGAL) were measured preoperatively, postoperatively (post-op), and at the first (D1) and second (D2) post-op day. AKI was defined as an increase of sCr to ≥1.5-fold from baseline within 2 days after surgery. <b><i>Results:</i></b> Of the 52 patients studied, 10 patients (19%) developed AKI. Patients with AKI were older (69.6 ± 10.7 vs. 58.1 ± 16.7 years, <i>p</i> = 0.043) and had a longer length of ICU stay (13 [IQR 6–49] vs. 6 [IQR 5–8] days, <i>p</i> = 0.032). Between the 2 groups, the evolution of BTP, sCr, CysC, and NGAL over time differed significantly, with overall higher values in the AKI group. ROC analysis for the detection of AKI within 2 days after surgery showed a great accuracy for BTP. The area under the curve (AUC) for BTP post-op; D1; and D2 was, respectively, 0.869 ± 0.049; 0.938 ± 0.035; and 0.943 ± 0.032. The discriminative power of a BTP measurement on D1 was superior in detecting AKI compared to NGAL (adjusted <i>p</i> value = 0.027). We could not detect a significant difference between the AUCs of other biomarkers (NGAL, sCr, and CysC). <b><i>Conclusion:</i></b> Serum BTP is a promising marker for diagnosing AKI in ICU patients undergoing surgery.

scholarly journals Diagnostic Value of C-Reactive Protein in Discrimination between Uncomplicated and Complicated Parapneumonic Effusion

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 829
Author(s):  
Yana Kogan ◽  
Edmond Sabo ◽  
Majed Odeh
Keyword(s):  
Area Under The Curve ◽  
Diagnostic Value ◽  
Parapneumonic Effusion ◽  
C Reactive Protein ◽  
Diagnostic Efficacy ◽  
Reactive Protein ◽  
Significant Difference ◽  
Study Population ◽  
Complicated Parapneumonic Effusion

Objectives: The role of serum C-reactive protein (CRPs) and pleural fluid CRP (CRPpf) in discriminating uncomplicated parapneumonic effusion (UCPPE) from complicated parapneumonic effusion (CPPE) is yet to be validated since most of the previous studies were on small cohorts and with variable results. The role of CRPs and CRPpf gradient (CRPg) and of their ratio (CRPr) in this discrimination has not been previously reported. The study aims to assess the diagnostic efficacy of CRPs, CRPpf, CRPr, and CRPg in discriminating UCPPE from CPPE in a relatively large cohort. Methods: The study population included 146 patients with PPE, 86 with UCPPE and 60 with CPPE. Levels of CRPs and CRPpf were measured, and the CRPg and CRPr were calculated. The values are presented as mean ± SD. Results: Mean levels of CRPs, CRPpf, CRPg, and CRPr of the UCPPE group were 145.3 ± 67.6 mg/L, 58.5 ± 38.5 mg/L, 86.8 ± 37.3 mg/L, and 0.39 ± 0.11, respectively, and for the CPPE group were 302.2 ± 75.6 mg/L, 112 ± 65 mg/L, 188.3 ± 62.3 mg/L, and 0.36 ± 0.19, respectively. Levels of CRPs, CRPpf, and CRPg were significantly higher in the CPPE than in the UCPPE group (p < 0.0001). No significant difference was found between the two groups for levels of CRPr (p = 0.26). The best cut-off value calculated by the receiver operating characteristic (ROC) analysis for discriminating UCPPE from CPPE was for CRPs, 211.5 mg/L with area under the curve (AUC) = 94% and p < 0.0001, for CRPpf, 90.5 mg/L with AUC = 76.3% and p < 0.0001, and for CRPg, 142 mg/L with AUC = 91% and p < 0.0001. Conclusions: CRPs, CRPpf, and CRPg are strong markers for discrimination between UCPPE and CPPE, while CRPr has no role in this discrimination.

scholarly journals LTBP1 promotes fibrillin incorporation into the extracellular matrix

2021 ◽  
Author(s):  
Matthias Przyklenk ◽  
Veronika Georgieva ◽  
Fabian Metzen ◽  
Sebastian Mostert ◽  
Birgit Kobbe ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Protein ◽  
Wide Spectrum ◽  
Extracellular Matrix Protein ◽  
Connective Tissues ◽  
Pathogenic Variants ◽  
Human Pathology ◽  
Fibrillin 1

LTBP1 is a large extracellular matrix protein and an associated ligand of fibrillin-microfibrils. Knowledge of LTBP1 functions is largely limited to its role in targeting and sequestering TGFβ growth factors within the extracellular matrix, thereby regulating their bioavailability. However, the recent description of a wide spectrum of phenotypes in multiple tissues in patients harboring LTBP1 pathogenic variants suggests a multifaceted role of the protein in the homeostasis of connective tissues. To better understand the human pathology caused by LTBP1 deficiency it is important to investigate its functional role in extracellular matrix formation. In this study, we show that LTBP1 coordinates the incorporation of fibrillin-1 and -2 into the extracellular matrix in vitro. We also demonstrate that this function is differentially exerted by the two isoforms, the short and long forms of LTBP1. Thereby our findings uncover a novel TGFβ-independent LTBP1 function potentially contributing to the development of connective tissue disorders.

scholarly journals Study on the Distribution Characteristics and Influencing Factors of Homocysteine in the Physical Examination Population

2021 ◽  
Author(s):  
Fang Bao ◽  
Ming Cui ◽  
Xiuying Shi ◽  
Shaoqing Ju ◽  
Hui Cong
Keyword(s):  
Blood Pressure ◽  
Physical Examination ◽  
Large Scale ◽  
Kidney Injury ◽  
Scientific Basis ◽  
Cerebrovascular Diseases ◽  
Health Examination ◽  
Significant Difference ◽  
The Difference

Abstract Background: Homocysteine (Hcy) is considered to be an independent risk factor for cardiovascular and cerebrovascular diseases. No study has evaluated the distribution of Hcy on a large-scale health examination. Accordingly, this study aimed to investigate the level and distribution of Hcy in the healthy physical examination population and the correlation with other biomarkers, and analyzed for cardiovascular and other diseases. The prevention provides an important scientific basis.Methods: From February 2017 to April 2020, 8063 medical examination populations were selected for analysis. Determination of serum Hcy, TC, TG, LDL-c, HDL-c, ALT, ALP, γ-GT, TBIL, GLU, urea, Cr, UA and related metabolic risk factors. According to the multivariate regression model of age, gender, smoking, drinking, body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP), the relationship between Hcy and other biochemical indicators was evaluated. Results: Among 8063 cases, the age, BMI, SBP and DBP of the high-Hcy group were higher than those of the low-Hcy group, the difference was statistically significant (P<0.05), and the proportion of males, smoking and drinking were higher than the low In the Hcy group, the difference was statistically significant (P<0.05); the ALT, ALP, γ-GT, TBIL, Urea, Cr, UA, and TG in the high Hcy group were higher than those in the low Hcy group, and the difference was statistically significant (P<0.05 ); HDL-c in the high-Hcy group was lower than that in the low-Hcy group, and the difference was statistically significant (P<0.05). There was no statistically significant difference in TC, LDL-c, and GLU between the high- and low-Hcy groups (P>0.05). In multivariate analysis, lnHDL-C was negatively correlated with lnHcy (β=-0.038, SE=0.016, P<0.05), lnCr was positively correlated with lnHcy (β=0.055, SE=0.016, P<0.05), lnUA and lnHcy were positive correlation (β=0.043, SE=0.019, P<0.05). Conclusion: Hcy is closely related to HDL-c, Cr and UA, which indicates that Hcy may affect the metabolism of HDL-c and UA, and can also be used as an auxiliary diagnostic index for kidney injury.

Abstract 474: ERK4-deficiency Potentiates the TAC-induced Increase in Collagen1-α 1 Messenger RNA in Mice

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Joelle Trepanier ◽  
Dharmendra D Dingar ◽  
Marc-Antoine Gillis ◽  
Pramod Sahadevan ◽  
Yan Fen Shi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Messenger Rna ◽  
Matrix Protein ◽  
Interstitial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Primary Source ◽  
Mitogen Activated Protein Kinase ◽  
Extracellular Matrix Protein ◽  
Systolic And Diastolic Function

Cardiac hypertrophy, a common consequence of cardiopathologies such as hypertension and myocardial infarcts, involves formation of excessive interstitial fibrosis, which may impair cardiac function. Fibroblasts are the primary source of extracellular matrix protein. Extracellular-regulated kinase 4 (ERK4) is an atypical mitogen-activated protein kinase (MAPK). The regulation and role of ERK4 in the heart are currently unidentified and its only known target is MAP kinase-activated protein kinase 5 (MK5), a kinase involved in regulating fibroblast function. Following constriction of the transverse aorta (TAC), MK5 haplodeficient mice showed an attenuation of the TAC-induced increase in collagen 1-α 1 mRNA at 2-wk post-TAC and reduced hypertrophy 8-wk post-TAC. Further studies revealed MK5 immunoreactivity in cardiac fibroblasts but not myocytes. MK5 immunoprecipitates from whole heart contain ERK3 immunoreactivity, but not that of ERK4 or p38 MAPK. This study was to examine the role of ERK4 in myocardial structure, function, and remodeling 3-wk post-TAC. At 12 wk of age, echocardiographic imaging revealed systolic and diastolic function in male ERK4 -/- mice were similar to wild-type littermates (ERK4 +/+ ). Three weeks post-TAC, hypertrophy was similar in ERK4 +/+ and ERK4 -/- mice. Transcripts for BNP and βMHC increased to similar extent in TAC- ERK4 +/+ and TAC- ERK4 -/- mice. Two-way ANOVA indicated that ERK4 deficiency altered the effect of TAC on TGFβ 1 and collagen 1-α 1 transcript levels with each being higher in TAC-ERK4 -/- mice. Furthermore, MK5 immunoprecipitates from cardiac fibroblast lysates did not contain ERK4 immunoreactivity. Additional experiments revealed the presence of ERK4 immunoreactivity in myocytes but not fibroblasts. These results suggest 1) ERK4 may be involved in myocyte - fibroblast communication during myocardial remodeling and 2) in cardiac myocytes, ERK4 is part of a novel signaling cascade that does not involve MK5.

Role of mesenchymal nidogen for epithelial morphogenesis in vitro

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 2003-2014 ◽  
Author(s):  
P. Ekblom ◽  
M. Ekblom ◽  
L. Fecker ◽  
G. Klein ◽  
H.Y. Zhang ◽  
...  
Keyword(s):  
Matrix Protein ◽  
Northern Blotting ◽  
Epithelial Morphogenesis ◽  
Extracellular Matrix Protein ◽  
Epithelial Development ◽  
Morphogenesis In Vitro ◽  
Development In Vitro ◽  
Membrane Components

Recent biochemical studies suggested that the extracellular matrix protein nidogen is a binding molecule linking together basement membrane components. We studied its expression and role during development. By immunofluorescence and northern blotting, nidogen was found early during epithelial cell development of kidney and lung. Yet, in situ hybridization revealed that nidogen was not produced by epithelium but by the adjacent mesenchyme in both organs. Binding of mesenchymal nidogen to epithelial laminin may thus be a key event during epithelial development. This is supported by antibody perturbation experiments. Antibodies against the nidogen binding site on laminin B2 chain perturbed epithelial development in vitro in embryonic kidney and lung. Mesenchymal nidogen could be important for early stages of epithelial morphogenesis.

scholarly journals Validation of PELOD-2 score as a predictor of life-threatening organ dysfunction in pediatric sepsis

2020 ◽  
Vol 60 (5) ◽  
pp. 227-32
Author(s):  
Yuyun Romaria Simanjuntak ◽  
Indra Saputra ◽  
Silvia Triratna ◽  
Achirul Bakri ◽  
Yulia Iriani
Keyword(s):  
Organ Dysfunction ◽  
Roc Curve ◽  
Area Under The Curve ◽  
Youden Index ◽  
International Consensus ◽  
Failure Assessment ◽  
Life Threatening ◽  
Sepsis Definition ◽  
Pediatric Sepsis ◽  
Sepsis And Septic Shock

Background The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction due to immune dysregulation against infection. It recommends the Sequential (sepsis-related) Organ Failure Assessment (SOFA) score to evaluate life-threatening organ dysfunction. But the SOFA tool has not been adjusted for pediatric patients.  The Indonesian Pediatrics Society (IPS) uses the same sepsis definition and recommends using the PELOD-2 score as an indicator of life-threatening organ dysfunction in children.     Objective To evaluate the validity of the PELOD-2 score for predicting life-threatening organ dysfunction in pediatric sepsis. Methods A prospective cohort study was conducted in children with sepsis who were admitted to the PICU.  Subjects were taken consecutively with inclusion criteria of 1 month-18 years of age, with organ dysfunction, having two or more symptoms of systemic inflammatory response syndrome (SIRS), and suspected or proven infection.  PELOD-2 score, with and without lactate result, of each subject were plotted to receiver operating characteristic (ROC) curve, then we determined the most optimal cut off point to predict the life-threathneing organ dysfunction in pediatric sepsis based on the sensitivity and specificity of each score. Results Sixty-six patients were analyzed, with 40 males and 26 females aged 2 to 183 months (median 11 months).  Twenty patients died while in the PICU. A PELOD-2 score (with lactate) cut-off ≥ 7 was determined by ROC curve, with sensitivity of 80% and specificity of 78%. The area under the curve (AUC) of PELOD-2 score (with lactate) was 84.8% (95%CI 74.7 to 95.9%).  A PELOD-2 score (without lactate) ≥ 7  was the most optimum cut off based on its Youden index, it haD 70% of sensitivity and 80% of specificity. Conclusion PELOD-2 score ≥ 7 , with or without lactate component is the optimal cut-off for predicting life-threatening organ dysfunction in pediatric sepsis. 

scholarly journals The clinical spectrum of the congenital myasthenic syndrome resulting from COL13A1 mutations

Brain ◽  
2019 ◽  
Vol 142 (6) ◽  
pp. 1547-1560 ◽  
Author(s):  
Pedro M. Rodríguez Cruz ◽  
Judith Cossins ◽  
Eduardo de Paula Estephan ◽  
Francina Munell ◽  
Kathryn Selby ◽  
...  
Keyword(s):  
Muscle Strength ◽  
Matrix Protein ◽  
Neuromuscular Synapse ◽  
Extracellular Matrix Protein ◽  
Congenital Myasthenic Syndrome ◽  
Facial Dysmorphism ◽  
Feeding Difficulties ◽  
Myasthenic Syndrome ◽  
Over Time

Abstract Next generation sequencing techniques were recently used to show mutations in COL13A1 cause synaptic basal lamina-associated congenital myasthenic syndrome type 19. Animal studies showed COL13A1, a synaptic extracellular-matrix protein, is involved in the formation and maintenance of the neuromuscular synapse that appears independent of the Agrin-LRP4-MuSK-DOK7 acetylcholine receptor clustering pathway. Here, we report the phenotypic spectrum of 16 patients from 11 kinships harbouring homozygous or heteroallelic mutations in COL13A1. Clinical presentation was mostly at birth with hypotonia and breathing and feeding difficulties often requiring ventilation and artificial feeding. Respiratory crisis related to recurrent apnoeas, sometimes triggered by chest infections, were common early in life but resolved over time. The predominant pattern of muscle weakness included bilateral ptosis (non-fatigable in adulthood), myopathic facies and marked axial weakness, especially of neck flexion, while limb muscles were less involved. Other features included facial dysmorphism, skeletal abnormalities and mild learning difficulties. All patients tested had results consistent with abnormal neuromuscular transmission. Muscle biopsies were within normal limits or showed non-specific changes. Muscle MRI and serum creatine kinase levels were normal. In keeping with COL13A1 mutations affecting both synaptic structure and presynaptic function, treatment with 3,4-diaminopyridine and salbutamol resulted in motor and respiratory function improvement. In non-treated cases, disease severity and muscle strength improved gradually over time and several adults recovered normal muscle strength in the limbs. In summary, patients with COL13A1 mutations present mostly with severe early-onset myasthenic syndrome with feeding and breathing difficulties. Axial weakness is greater than limb weakness. Disease course improves gradually over time, which could be consistent with the less prominent role of COL13A1 once the neuromuscular junction is mature. This report emphasizes the role of collagens at the human muscle endplate and should facilitate the recognition of this disorder, which can benefit from pharmacological treatment.

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