Diagnosis and Risk Factors of Acute Kidney Injury in Very Low Birth Weight Infants

Acute kidney injury (AKI) is common in critically ill premature infants. There is a lack of consensus on the diagnostic definition of AKI in very low birth weight (VLBW) infants. The primary aim of this study was to determine the incidence and risk factors for AKI in VLBW infants using the AKI network (AKIN) and pRIFLE (pediatric Risk, Injury, Failure, Loss, End-Stage) criteria and to evaluate whether Clinical Risk Index for Babies (CRIB II) score is a predictor of AKI. The secondary objective was to determine the extent of agreement between the AKIN and pRIFLE criteria in the diagnosis of AKI in VLBW infants. Methods: This was a retrospective chart review of 115 VLBW (< 1500 g) infants born in an academic center with a Level 3B neonatal intensive care unit. Multiple congenital anomalies, transfer to other centers, or death within the first 2 weeks were the exclusion criteria. Relevant data were collected and analyzed in the first 2 weeks postnatally. Results: AKI incidence, according to AKIN and pRIFLE criteria, was 20.1% and 22.6%, respectively. As per the interrater reliability analysis, there was a fair agreement between the two criteria (kappa = 0.217). AKI was nonoliguric. The length of stay was significantly longer in the AKI group. Prenatal nonsteroidal anti-inflammatory drug exposure, lower gestational age, lower birth weight, respiratory distress syndrome, mechanical ventilation, patent ductus arteriosus, hypotension, late onset sepsis, and higher CRIB II scores were significantly associated with AKI. Our regression analysis found CRIB II scores to be an independent risk factor for AKI (odds ratio = 1.621; 95% confidence interval, 1.230–2.167; p = 0.001). Conclusion: The determination of AKI using the pRIFLE and AKIN criteria yielded different results. pRIFLE appears to be more sensitive in VLBW infants. A high CRIB II score was recorded for AKI. Future studies are necessary to develop a uniform definition and identify the risk factors to improve the outcomes in this population

A Rare Presentation of Isolated Congenital Splenic Hemangioma With Kasabach-Merritt Syndrome

Splenic hemangiomas (SHs) are the most common benign neoplasms of the spleen. However, they are rare in the newborn period. We present an extremely rare case of congenital SH complicated by Kasabach-Merritt syndrome. A 2.93 kg male infant was delivered at term with a prenatal diagnosis of a left infrarenal mass diagnosed by ultrasound at 35 weeks of gestation. Magnetic resonance imaging demonstrated a well-defined splenic mass with multiple flow voids and scattered areas of high intensity suggestive of hemorrhage. He developed anemia, thrombocytopenia, and coagulopathy which required transfusion with packed red cells, platelets, cryoprecipitate, and fresh frozen plasma. Excision biopsy of the spleen led to resolution of anemia, thrombocytopenia, and coagulopathy. The diagnosis of SH was confirmed by histopathology. At 2 months outpatient follow-up, the patient was growing well without any evidence of tumor recurrence. Congenital SH is a rare entity that can be fatal if the potential complication of Kasabach-Merritt syndrome is not anticipated, evaluated, and promptly treated. Our patient had a favorable outcome with early surgical excision of the SH

White Cell Indices and CRP: Predictors of Meningitis in Neonatal Sepsis?

Background Objective: To evaluate the utility of specific cut-off values for C- reactive protein (CRP) and immature-to-total neutrophil ratio (I/T) as screening tests for meningitis in culture negative early onset sepsis (EOS). Materials and Methods Retrospective chart review of 97 newborns with culture negative sepsis who had lumbar puncture performed as part of the sepsis evaluation in a level IIIB NICU at an academic medical center serving a predominantly minority population. Meningitis was defined as either a positive cerebrospinal fluid (CSF) culture or CSF WBC count ≥30/mm. The outcome measures were the sensitivity, specificity and predictive values of CRP >40 mg/L and I/T ratio >0.3 for diagnosing meningitis in newborns with EOS. Results The sensitivity, specificity and positive predictive value of I/T ratio >0.3, CRP >40 mg/L or a combination of these two either at 12 or 24 hours of life were very poor. However, CRP >40 mg/L alone or in combination with I/T ratio >0.3 at both 12 and 24 hours of life had negative predictive values of 85-90%. Conclusion CRP >40 mg/L and/or I/T ratio >0.3 have poor sensitivity, specificity and predictive values as screening tests for meningitis in culture negative early onset sepsis

TNFα-stimulated protein 6 (TSG-6) reduces lung inflammation in an experimental model of bronchopulmonary dysplasia

Inflammation is a key factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Tumor necrosis factor-stimulated protein 6 (TSG-6) is a glycoprotein that modulates inflammation. Here we tested the hypothesis that intra-tracheal (IT) administration of an adenovirus overexpressing TSG-6 (AdTSG-6) would decrease inflammation and restore lung structure in experimental BPD. Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O ) from postnatal day (P) 1-P14 were randomly assigned to receive IT AdTSG-6 or placebo (PL) on P3. The effect of IT AdTSG-6 on lung inflammation, alveolarization, angiogenesis, apoptosis, pulmonary vascular remodeling, and pulmonary hypertension were evaluated on P14. Data were analyzed by two-way ANOVA. TSG-6 mRNA was significantly increased in pups who received IT AdTSG-6. Compared to RA, hyperoxia PL-treated pups had increased NF-kβ activation and lung inflammation. In contrast, IT AdTSG-6 hyperoxia-treated pups had decreased lung phosphorylated NF-kβ expression and markers of inflammation. This was accompanied by an improvement in alveolarization, angiogenesis, pulmonary vascular remodeling, and pulmonary hypertension. IT AdTSG-6 decreases lung inflammation and improves lung structure in neonatal rats with experimental BPD. These findings suggest that therapies that increase lung TSG-6 expression may have beneficial effects in preterm infants with BPD

Caspase-1 Inhibition Attenuates Hyperoxia-induced Lung and Brain Injury in Neonatal Mice

Hyperoxia plays a key role in the development of bronchopulmonary dysplasia (BPD), a chronic lung disease of preterm infants. Infants with BPD often have brain injury that leads to long-term neurodevelopmental impairment, but the underlying mechanisms that control BPD-induced neurodevelopmental impairment remain unclear. Our previous studies have shown that hyperoxia-induced BPD in rodents is associated with lung inflammasome activation. Here, we tested the hypothesis that hyperoxia-induced lung and brain injury is mediated by inflammasome activation, and that inhibition of caspase-1, a key component of the inflammasome, attenuates hyperoxia-induced lung and brain injury in neonatal mice. C57/BL6 mouse pups were randomized to receive daily intraperitoneal injections of Ac-YVAD-CMK, an irreversible caspase-1 inhibitor, or placebo during exposure to room air or hyperoxia (85% O ) for 10 days. We found that hyperoxia activated the NLRP1 inflammasome, increased production of mature IL-1β, and upregulated expression of p30 gasdermin-D (GSDMD), the active form of GSDMD that is responsible for the programmed cell death mechanism of pyroptosis in both lung and brain tissue. Importantly, we show that inhibition of caspase-1 decreased IL-1β activation and p30 GSDMD expression, and improved alveolar and vascular development in hyperoxia-exposed lungs. Moreover, caspase-1 inhibition also promoted cell proliferation in the subgranular zone and subventricular zone of hyperoxia-exposed brains, resulting in lessened atrophy of these zones. Thus, the inflammasome plays a critical role in hyperoxia-induced neonatal lung and brain injury, and targeting this pathway may be beneficial for the prevention of lung and brain injury in preterm infants

Legislative Documents

Also, variously referred to as: Senate bills; Senate documents; Senate legislative documents; legislative documents; and General Court documents

Inhibition of Rac1 Signaling Downregulates Inflammasome Activation and Attenuates Lung Injury in Neonatal Rats Exposed to Hyperoxia

Inflammatory injury, particularly the production of active interleukin (IL)-1β plays a major role in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. The release of active IL-1β is controlled by posttranscriptional modifications of its proform (pro-IL-1β) through the inflammasome. Rac1 is a member of the Rho family of GTPases that regulate the inflammatory process. This study tested the hypothesis that Rac1 signaling increases inflammasome activation that results in damaging inflammation, and that the inhibition of Rac1 signaling prevents lung injury, by inhibiting inflammasome activation in a newborn rat model of BPD induced by hyperoxia. Newborn rat pups were exposed to room air or hyperoxia (85% O2) and received daily intraperitoneal injections of placebo (normal saline) or NSC23766, a specific Rac1 inhibitor, for 10 days. The effects on lung inflammation, alveolarization, vascular development, vascular remodeling, right ventricular systolic pressure, and right ventricular hypertrophy (RVH) were then assessed. Hyperoxia exposure upregulated Rac1 and increased the production of active IL-1β, which was accompanied by increasing expression of the inflammasome. In addition, hyperoxia induced the pathological hallmarks of BPD. However, treatment with NSC23766 significantly decreased inflammasome activation and macrophage infiltration, improved alveolar and vascular development, and reduced pulmonary vascular remodeling and RVH. These results indicate that Rac1 signaling regulates the expression of the inflammasome and plays a pivotal role in the pathogenesis of hyperoxia-induced neonatal lung injury. Therefore, targeting Rac1 signaling may provide a novel strategy to prevent and treat BPD in preterm infants

Riociguat reduces hyperoxia-induced PH.

<p>(<b>A</b>) Right ventricular systolic pressure (RVSP) was significantly increased in the hyperoxia + placebo treated group as compared with normoxia group. Riociguat administration significantly decreased RVSP during hyperoxia. ***<i>P</i> < 0.001 compared with normoxia; ⁺<i>P</i> < 0.05 compared with hyperoxia + placebo (n = 6/group). (<b>B</b>) Right ventricular hypertrophy (RVH), also known as the Fulton’s index, was determined by the weight ratio of right ventricle (RV) to left ventricle + septum (LV + S). Hyperoxia exposed animals in the presence of placebo showed significant RVH as compared with normoxia group. Administration of riociguat decreased RVH in hyperoxia exposed lungs. ***<i>P</i> < 0.001 compared with normoxia; ⁺⁺<i>P</i> < 0.01 compared with hyperoxia + placebo (n = 6/group).</p