The aim of this study was to better define, by immunohistochemistry, the molecular markers of ren... more The aim of this study was to better define, by immunohistochemistry, the molecular markers of renal stem/progenitor cells localized in the different niches of ten human preterm kidneys with gestational age ranging from 11 up to 25 weeks. Our data evidence the existence of multiple stem/progenitor pools in different zones of the human developing kidney that are characterized by different phenotypes: capsular stem cells were EMA (MUC1)+, MDM2+, Vimentin+ and Wnt1+; progenitors of the sub-capsular nephrogenic zone were MDM2+ and Wnt1+; cap mesenchymal cells were EMA (MUC1)+, CD15+, vimentin+, Wt1+, CD10+, Bcl2+, Wnt1+ and PAX2+; interstitial progenitor cells were Vimentin+, Wt1+ and α1Anti-tripsin+. Our data evidence the existence of multiple stem/progenitor cell pools in the fetal and neonatal human kidney. Progenitors of these different pools are characterized by a peculiar phenotype, indicating a different differentiation stage of these renal progenitors. A better knowledge of the m...
Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care... more Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p=0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS.
The development of the mammalian kidney is a complex and in part unknown process which requires i... more The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal-epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth.
Journal of Maternal-Fetal and Neonatal Medicine, 2011
The survival rate for extremely low birth weight (ELBW) infants born preterm is on an increasing ... more The survival rate for extremely low birth weight (ELBW) infants born preterm is on an increasing upward trend, despite the possibility of neuro-cerebral consequences in later life. To date, scarce information is available on the effect of extreme prematurity on cardiovascular system. To verify the presence of standard echocardiographic and ECG alterations in ex-ELBW young healthy adults. A color Doppler echocardiogram and an ECG were performed on 24 ex-ELBW (4 males and 20 females; mean: 23.2 ± 3.3 years), compared with 24 healthy subjects born at term (C). ECG parameters examined: PR, QT, QT(c), and QT dispersion (QT(d)). Gestational age, birth weight, and duration of stay in neonatal intensive care unit were obtained from clinical records. Transthoracic echocardiography did not reveal differences between ex-ELBW and C, while a significant difference was displayed by ex-ELBW with regard to PR (141.5 ± 13.4 ms vs. 164.2 ± 24.0 ms, p < 0.0003), QT(c) (417.0 ± 23.6 ms vs. 369.9 ± 19.5 ms, p =0.00001), and QT(d) (30.4 ± 14.1 ms vs. 24.6 ± 8.2 ms, p < 0.00001). In two patients (8.3%), QT(c) exceeded the upper limit of normal range. A statistically significant inverse correlation was observed between QT(c) and gestational age (r = -0.67, p < 0.0003). QT(c) and QT(d) in ex-ELBW were found to be at the upper limit of normal range and correlated with gestational age and birth weight; in two cases, QT(c) exceeded the upper limit. This study, irrespective of the pathophysiological mechanism involved, underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval. QT(c) and QT(d) in young adults previously born preterm with an ELBW (401-1000 g) were generally found to be at the upper limit of normal range and correlated with gestational age and birth weight. This finding underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval.
Journal of Maternal-Fetal and Neonatal Medicine, 2013
The cardiovascular vulnerability of young adults who were born preterm was first acknowledged ove... more The cardiovascular vulnerability of young adults who were born preterm was first acknowledged over a decade ago. (1) To examine the echocardiographic characteristics of a group of young adults born preterm with an extremely low birthweight (<1000 g; ex-ELBW) in comparison with healthy controls born at term (C); (2) to identify a correlation between the potential echocardiographic abnormalities detected in ex-ELBW and their anthropometric parameters, age, presence of respiratory distress, patency of ductus arteriosus, length of stay in Neonatal Intensive Care Unit. Thirty-seven ex-ELBW (11 males, 26 females; mean age: 22.2 ± 1.8 years) were compared with 37 C (11 males, 26 females). Both groups underwent standard mono- and bi-dimensional transthoracic echocardiogram with color Doppler. No statistically significant differences were detected between the two groups regarding mono-dimensional echocardiography or Doppler measurements (p = ns). Conversely, a statistically significant difference was observed between the prevalence of interatrial septal aneurysm (ASA) in ex-ELBW compared to C (p = 0.0016). A significant association was likewise observed between ASA and the presence of both respiratory distress at birth (p < 0.05) and patency of the ductus arteriosus (p < 0.05). A significant prevalence of ASA was detected in ex-ELBW subjects compared to C, underlining a probable correlation with respiratory distress and patent ductus arteriosus. In view of the association between ASA and stroke in young adults devoid of other cerebrovascular risk factors, this unexpected observation suggests that all ex-preterm subjects should undergo transthoracic or transesophageal echocardiographic examination with the aim of detecting this potentially emboligenic cardiac abnormality.
The aim of this study was to better define, by immunohistochemistry, the molecular markers of ren... more The aim of this study was to better define, by immunohistochemistry, the molecular markers of renal stem/progenitor cells localized in the different niches of ten human preterm kidneys with gestational age ranging from 11 up to 25 weeks. Our data evidence the existence of multiple stem/progenitor pools in different zones of the human developing kidney that are characterized by different phenotypes: capsular stem cells were EMA (MUC1)+, MDM2+, Vimentin+ and Wnt1+; progenitors of the sub-capsular nephrogenic zone were MDM2+ and Wnt1+; cap mesenchymal cells were EMA (MUC1)+, CD15+, vimentin+, Wt1+, CD10+, Bcl2+, Wnt1+ and PAX2+; interstitial progenitor cells were Vimentin+, Wt1+ and α1Anti-tripsin+. Our data evidence the existence of multiple stem/progenitor cell pools in the fetal and neonatal human kidney. Progenitors of these different pools are characterized by a peculiar phenotype, indicating a different differentiation stage of these renal progenitors. A better knowledge of the m...
Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care... more Neonatal sepsis still remains a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); and 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3days after the start of antibiotic treatment. sCD14-ST presepsin was measured by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p=0.730). In our population, CRP and sCD14-ST did not correlate with each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95% C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS.
The development of the mammalian kidney is a complex and in part unknown process which requires i... more The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal-epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth.
Journal of Maternal-Fetal and Neonatal Medicine, 2011
The survival rate for extremely low birth weight (ELBW) infants born preterm is on an increasing ... more The survival rate for extremely low birth weight (ELBW) infants born preterm is on an increasing upward trend, despite the possibility of neuro-cerebral consequences in later life. To date, scarce information is available on the effect of extreme prematurity on cardiovascular system. To verify the presence of standard echocardiographic and ECG alterations in ex-ELBW young healthy adults. A color Doppler echocardiogram and an ECG were performed on 24 ex-ELBW (4 males and 20 females; mean: 23.2 ± 3.3 years), compared with 24 healthy subjects born at term (C). ECG parameters examined: PR, QT, QT(c), and QT dispersion (QT(d)). Gestational age, birth weight, and duration of stay in neonatal intensive care unit were obtained from clinical records. Transthoracic echocardiography did not reveal differences between ex-ELBW and C, while a significant difference was displayed by ex-ELBW with regard to PR (141.5 ± 13.4 ms vs. 164.2 ± 24.0 ms, p < 0.0003), QT(c) (417.0 ± 23.6 ms vs. 369.9 ± 19.5 ms, p =0.00001), and QT(d) (30.4 ± 14.1 ms vs. 24.6 ± 8.2 ms, p < 0.00001). In two patients (8.3%), QT(c) exceeded the upper limit of normal range. A statistically significant inverse correlation was observed between QT(c) and gestational age (r = -0.67, p < 0.0003). QT(c) and QT(d) in ex-ELBW were found to be at the upper limit of normal range and correlated with gestational age and birth weight; in two cases, QT(c) exceeded the upper limit. This study, irrespective of the pathophysiological mechanism involved, underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval. QT(c) and QT(d) in young adults previously born preterm with an ELBW (401-1000 g) were generally found to be at the upper limit of normal range and correlated with gestational age and birth weight. This finding underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval.
Journal of Maternal-Fetal and Neonatal Medicine, 2013
The cardiovascular vulnerability of young adults who were born preterm was first acknowledged ove... more The cardiovascular vulnerability of young adults who were born preterm was first acknowledged over a decade ago. (1) To examine the echocardiographic characteristics of a group of young adults born preterm with an extremely low birthweight (<1000 g; ex-ELBW) in comparison with healthy controls born at term (C); (2) to identify a correlation between the potential echocardiographic abnormalities detected in ex-ELBW and their anthropometric parameters, age, presence of respiratory distress, patency of ductus arteriosus, length of stay in Neonatal Intensive Care Unit. Thirty-seven ex-ELBW (11 males, 26 females; mean age: 22.2 ± 1.8 years) were compared with 37 C (11 males, 26 females). Both groups underwent standard mono- and bi-dimensional transthoracic echocardiogram with color Doppler. No statistically significant differences were detected between the two groups regarding mono-dimensional echocardiography or Doppler measurements (p = ns). Conversely, a statistically significant difference was observed between the prevalence of interatrial septal aneurysm (ASA) in ex-ELBW compared to C (p = 0.0016). A significant association was likewise observed between ASA and the presence of both respiratory distress at birth (p < 0.05) and patency of the ductus arteriosus (p < 0.05). A significant prevalence of ASA was detected in ex-ELBW subjects compared to C, underlining a probable correlation with respiratory distress and patent ductus arteriosus. In view of the association between ASA and stroke in young adults devoid of other cerebrovascular risk factors, this unexpected observation suggests that all ex-preterm subjects should undergo transthoracic or transesophageal echocardiographic examination with the aim of detecting this potentially emboligenic cardiac abnormality.
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