Evaluation of neutropenia and neutrophilia in preterm infants

OBJECTIVE: Neutrophil counts are used routinely as part of the sepsis evaluation in newborn infants. In this article, we review the normal blood neutrophil concentrations and the clinical approach to neutropenia and neutrophilia in the neonatal period. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Neutropenia and neutrophilia are documented frequently in premature infants. Neutropenia can be seen in up to 8% of all infants admitted to neonatal intensive care. Neutrophilia is even more common, reported in up to 40% of all preterm infants. CONCLUSIONS: Neutrophil counts should be carefully evaluated in premature neonates. Maternal and perinatal history, physical examination, and a limited laboratory assessment is usually adequate for making a diagnosis in most infants

Association between red cell transfusions and necrotizing enterocolitis

OBJECTIVE: Several case reports and retrospective studies have reported a temporal association between red blood cell (RBC) transfusions and necrotizing enterocolitis (NEC). In this article, we review the clinical evidence and biological plausibility of the association between RBC transfusions and NEC. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Among all cases of NEC, 25 -40% patients were noted to have received an RBC transfusion within a 48 hour period prior to onset of NEC. Compared to infants who developed NEC unrelated to transfusion, neonates with transfusion-associated NEC were born at an earlier gestation, had lower birth weights, and had a delayed onset at 3-5 weeks of postnatal age. CONCLUSIONS: Based on current clinical evidence, transfusion-associated NEC appears to be a plausible clinical entity. However, there is a need for cautious interpretation of data because all the studies that have been conducted until date are retrospective, and therefore, susceptible to bias. A large, prospective, multi-center trial is needed to evaluate the association between RBC transfusion and NEC

Combination therapy for severe portopulmonary hypertension in a child allows for liver transplantation

Severe PPHTN is a contraindication to liver transplantation and predicts an abysmal 5‐year outcome. It is defined as a resting mPAP >45 mm Hg with a mean pulmonary artery wedge pressure of 3 wood units in the setting of portal hypertension. There have been limited reports of successful treatment of PPHTN leading to successful liver transplantation in adults, and one reported use of monotherapy as a bridge to successful liver transplant in pediatrics. To our knowledge, we describe the first use of combination therapy as a successful bridge to liver transplantation in a pediatric patient with severe PPHTN. This report adds to the paucity of data in pediatrics on the use of pulmonary vasodilator therapy in patients with severe PPHTN as a bridge to successful liver transplantation. Early diagnosis in order to mitigate or avoid the development of irreversible pulmonary vasculopathy that would preclude candidacy for liver transplantation is crucial, but our report demonstrates that combination therapy can be administered safely, quickly, and may allow for successful liver transplantation in patients with severe PPHTN

Clinically Actionable Hypercholesterolemia and Hypertriglyceridemia in Children with Nonalcoholic Fatty Liver Disease

OBJECTIVE: To determine the percentage of children with nonalcoholic fatty liver disease (NAFLD) in whom intervention for low-density lipoprotein cholesterol or triglycerides was indicated based on National Heart, Lung, and Blood Institute guidelines. STUDY DESIGN: This multicenter, longitudinal cohort study included children with NAFLD enrolled in the National Institute of Diabetes and Digestive and Kidney Diseases Nonalcoholic Steatohepatitis Clinical Research Network. Fasting lipid profiles were obtained at diagnosis. Standardized dietary recommendations were provided. After 1 year, lipid profiles were repeated and interpreted according to National Heart, Lung, and Blood Institute Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction. Main outcomes were meeting criteria for clinically actionable dyslipidemia at baseline, and either achieving lipid goal at follow-up or meeting criteria for ongoing intervention. RESULTS: There were 585 participants, with a mean age of 12.8 years. The prevalence of children warranting intervention for low-density lipoprotein cholesterol at baseline was 14%. After 1 year of recommended dietary changes, 51% achieved goal low-density lipoprotein cholesterol, 27% qualified for enhanced dietary and lifestyle modifications, and 22% met criteria for pharmacologic intervention. Elevated triglycerides were more prevalent, with 51% meeting criteria for intervention. At 1 year, 25% achieved goal triglycerides with diet and lifestyle changes, 38% met criteria for advanced dietary modifications, and 37% qualified for antihyperlipidemic medications. CONCLUSIONS: More than one-half of children with NAFLD met intervention thresholds for dyslipidemia. Based on the burden of clinically relevant dyslipidemia, lipid screening in children with NAFLD is warranted. Clinicians caring for children with NAFLD should be familiar with lipid management

Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

BACKGROUND: Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays. METHODS AND FINDINGS: Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment. CONCLUSIONS: Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features

In Children with Nonalcoholic Fatty Liver Disease, Zone 1 Steatosis is Associated with Advanced Fibrosis

Background & Aims Focal zone 1 steatosis, although rare in adults with nonalcoholic fatty liver disease (NAFLD), does occur in children with NAFLD. We investigated whether focal zone 1 steatosis and focal zone 3 steatosis are distinct subphenotypes of pediatric NAFLD. We aimed to determine associations between the zonality of steatosis and demographic, clinical, and histologic features in children with NAFLD. Methods We performed a cross-sectional study of baseline data from 813 children (age <18 years; mean age, 12.8 ± 2.7 years). The subjects had biopsy-proven NAFLD and were enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network. Liver histology was reviewed using the Nonalcoholic Steatohepatitis Clinical Research Network scoring system. Results Zone 1 steatosis was present in 18% of children with NAFLD (n = 146) and zone 3 steatosis was present in 32% (n = 244). Children with zone 1 steatosis were significantly younger (10 vs 14 years; P < .001) and a significantly higher proportion had any fibrosis (81% vs 51%; P < .001) or advanced fibrosis (13% vs 5%; P < .001) compared with children with zone 3 steatosis. In contrast, children with zone 3 steatosis were significantly more likely to have steatohepatitis (30% vs 6% in children with zone 1 steatosis; P < .001). Conclusions Children with zone 1 or zone 3 distribution of steatosis have an important subphenotype of pediatric NAFLD. Children with zone 1 steatosis are more likely to have advanced fibrosis and children with zone 3 steatosis are more likely to have steatohepatitis. To achieve a comprehensive understanding of pediatric NAFLD, studies of pathophysiology, natural history, and response to treatment should account for the zonality of steatosis

Haematological abnormalities in neonatal necrotizing enterocolitis

OBJECTIVE: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants born prior to 32 weeks gestation or with a birth weight less than 1500 grams. In this article, we review hematological abnormalities associated with NEC. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Thrombocytopenia, disseminated intravascular coagulation, increased or decreased neutrophil counts, and hemolytic anemia are frequent events in NEC. CONCLUSIONS: NEC is associated with several hematological abnormalities, which may play a direct or indirect role in the pathogenesis of gut mucosal injury, and may also carry important prognostic information

Evaluation of neutropenia and neutrophilia in preterm infants

OBJECTIVE: Neutrophil counts are used routinely as part of the sepsis evaluation in newborn infants. In this article, we review the normal blood neutrophil concentrations and the clinical approach to neutropenia and neutrophilia in the neonatal period. METHODS: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. RESULTS: Neutropenia and neutrophilia are documented frequently in premature infants. Neutropenia can be seen in up to 8% of all infants admitted to neonatal intensive care. Neutrophilia is even more common, reported in up to 40% of all preterm infants. CONCLUSIONS: Neutrophil counts should be carefully evaluated in premature neonates. Maternal and perinatal history, physical examination, and a limited laboratory assessment is usually adequate for making a diagnosis in most infants

Hematological Abnormalities in Neonatal Necrotizing Enterocolitis

Objective: Necrotizing enterocolitis (NEC) is a leading cause of morbidity and mortality in preterm infants born prior to 32 weeks gestation or with a birth weight less than 1500 grams. In this article, we review hematological abnormalities associated with NEC. Methods: A literature search was performed using the databases PubMed, EMBASE, and Scopus, and the electronic archive of abstracts presented at the annual meetings of the Pediatric Academic Societies. Results: Thrombocytopenia, disseminated intravascular coagulation, increased or decreased neutrophil counts, and hemolytic anemia are frequent events in NEC. Conclusions: NEC is associated with several hematological abnormalities, which may play a direct or indirect role in the pathogenesis of gut mucosal injury. Some of these abnormalities carry important prognostic information

Analog Integrated Audio Frequency Synthesizer

In this paper we present an audio synthesizer that creates audio signals, intended to be reproduced as sound by a loudspeaker. This paper details the design, implementation and verification of an analog, subtractive audio synthesizer. The synthesizer produces a variety of waveforms spanning approximately 3 octaves. The frequency is controlled by an external voltage and the harmonic content is regulated by a tunable filter. The system is fabricated in 130 nm CMOS. Current consumption measures between 1.8 and 2.1 mA from a supply of 1.2 V