Impact of Early Initiation of Enteral Nutrition on Survival During Pediatric Extracorporeal Membrane Oxygenation

Introduction: Pediatric data related to safety, tolerance, and outcomes of enteral nutrition (EN) for patients requiring extracorporeal membrane oxygenation (ECMO) are lacking. The objectives of this study were to evaluate early nutrition status and timing of EN initiation on survival during pediatric ECMO. Methods: A single center institutional review board–approved retrospective chart review was performed on all pediatric patients requiring ECMO from October 2008 through December 2013. Demographics, ECMO variables, laboratory values, vasoactive inotropic score (VIS), and nutrition data on day 5 (d5) were collected. Patients receiving parenteral nutrition (PN) were compared with those receiving any EN on d5. Analyses were conducted to identify factors influencing survival to completion of ECMO and to discharge. Results: Forty‐nine patients aged 53 ± 76 months met inclusion criteria. Kaplan‐Meier curves demonstrated greater survival to discharge in patients receiving any EN, compared with only receiving PN (P = .031). EN on d5 of ECMO support (P = .040) and a higher percentage of daily energy intake achieved (P = .013) were protective, whereas a higher VIS was associated with increased mortality (P = .010). Multivariable analysis demonstrated EN was no longer associated with survival to discharge (P = .139), whereas energy intake (P = .021) and VIS (P = .013) remained significant. Conclusions: Pediatric patients who received nutrition that was closer to goal energy intake, as well as those who received any EN early during ECMO, had improved survival to hospital discharge.     

Obesity: Risk Factor for Increased Resource Utilization at Bidirectional Glenn

Background

Underweight infants with single‐ventricle cardiac physiology have been shown to have increased morbidity, mortality, and resource utilization. The purpose of this study was to determine whether patients who were overweight, as defined by weight‐for‐length z score >90th percentile, were similarly at risk for increased resource utilization, as defined by mechanical ventilation hours (VHs) and intensive care unit length of stay (ICU LOS).

Methods

We evaluated resource utilization for 109 patients from our institution who underwent bidirectional Glenn surgery from January 2010 to June 2015 and met prespecified inclusion criteria. Patients were divided into 3 groups: underweight (z score, <5th percentile), normal weight (z score, 5th–90th percentile), and overweight (z score, >90th percentile).

Results

ICU LOS was longer in the overweight group (median, 18.5 days) when compared with the under‐ and normal‐weight groups (median LOS, 11 and 9 days, respectively) but did not reach statistical significance. VHs were also increased in the overweight group (median, 72 hours) when compared with the underweight (median, 27 hours) and normal weight (median, 25 hours) groups. This increase in VHs was statistically significant (P = .03).

Conclusions

This study suggests that patients with single‐ventricle physiology who are overweight at the time of their bidirectional Glenn surgery may be at risk for increased resource utilization as compared with those who meet or fail to meet their caloric recommendations. These findings represent an underappreciated risk factor in this already‐vulnerable patient population, providing potential opportunity for intervention and improved outcomes.     

Splenic trauma: evaluation with contrast-specific sonography and a second-generation contrast medium: preliminary experience.

OBJECTIVE: To report our experience in the assessment of splenic trauma with contrast-coded sonography and a second-generation contrast medium. METHODS: From January to May 2002, 120 patients were studied with sonography for suspected splenic trauma. Twenty-five were selected for further imaging because of sonographic findings positive for splenic injury, findings positive for peritoneal fluid only, indeterminate findings, and negative findings with high clinical or laboratory suspicion. These patients underwent contrast-enhanced harmonic sonography and contrast-enhanced helical computed tomography. RESULTS: Among the 25 patients studied, 6 had no spleen trauma at initial and follow-up evaluation. One patient had a hypoperfused spleen without parenchymal damage, and 18 had splenic injuries; these 19 patients were considered positive. Hemoperitoneum was identified by sonography, contrast-enhanced sonography, and contrast-enhanced computed tomography in 74% of the 19 positive cases. Perisplenic clots were recognized in 58% of the cases by computed tomography and in 42% by baseline and enhanced sonography. Splenic infarctions were found in 11% of cases by contrast-enhanced sonography and computed tomography; none was found by unenhanced sonography. Parenchymal traumatic lesions were identified in 12 of 18 patients with splenic injuries by unenhanced sonography, in 17 cases by contrast-enhanced sonography, and in all 18 cases by contrast-enhanced computed tomography. A minimal splenic lesion was found in the single patient with a false-negative contrast-enhanced sonographic finding. Contrast-enhanced sonography correlated appreciably better than unenhanced sonography in detecting injuries and in estimating their extent. Findings undetectable on unenhanced sonography were also noted: splenic hypoperfusion in 11% of positive cases on both contrast-enhanced sonography and contrast-enhanced computed tomography, contrast medium pooling in 21% of cases on both contrast-enhanced sonography and computed tomography, and contrast extravasation in 11% of cases on computed tomography and 5% on contrast-enhanced sonography. CONCLUSIONS: Contrast-enhanced sonography is a promising tool in the assessment of splenic trauma. In institutions where sonography is used as the initial procedure, this technique may increase its effectiveness.     

Combination therapy in rheumatoid arthritis: updated systematic review

In a second update of a systematic review, many new developments in the combined drug treatment of rheumatoid arthritis (RA) are highlighted. In early RA patients, step-down bridge therapy that includes corticosteroids leads to much enhanced efficacy at acceptable or low toxicity. The effects on joint damage may be persistent, but the symptomatic effects are probably dependent on continued corticosteroid dosing. In late patients, cyclosporin improves a suboptimal clinical response to methotrexate, and the triple combination of methotrexate, sulphasalazine and hydroxychloroquine appears to be clinically better than the components. Other combinations are either untested, tested at low sample size, or show negative interaction. In view of the low volume of evidence, most studies need confirmation by replication.      

Administration of recombinant human granulocyte-macrophage colony- stimulating factor after chemotherapy regulates the expression and secretion of monocyte tumor necrosis factor (TNF) and TNF receptors p55 and p75

Monocyte expression and secretion of tumor necrosis factor (TNF) and TNF receptors (TNF-R) p55 and p75 was studied in patients receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) after intensive chemotherapy. TNF expression and secretion of biologically active TNF was increased at regeneration compared with that of patients who had received chemotherapy alone. This effect persisted for several weeks after cessation of growth factor therapy. GM-CSF restored the responsiveness of monocytes to bacterial lipopolysaccharide (LPS), which appeared to be diminished after chemotherapy alone. Expression and secretion of TNF-R p55 and p75 by monocytes was augmented by GM-CSF therapy in association with the increase in TNF protein. We propose that GM-CSF administration after chemotherapy restores the normal responsiveness of monocytes to a secondary stimulus such as LPS and primes monocytes to respond to LPS with increased expression and secretion of TNF and TNF-R.     

Triple negative breast cancer: looking for the missing link between biology and treatments

The so called “Triple Negative Breast Cancer” (TNBC) represents approximately 15-20% of breast cancers. This acronym simply means that the tumour does not express oestrogen receptor (ER) and progesterone receptor (PR) and does not exhibit amplification of the human epidermal growth factor receptor 2 (HER2) gene. Despite this unambiguous definition, TNBCs are an heterogeneous group of tumours with just one common clinical feature: a distinctly aggressive nature with higher rates of relapse and shorter overall survival in the metastatic setting compared with other subtypes of breast cancer. Because of the absence of well-defined molecular targets, cytotoxic chemotherapy is currently the only treatment option for TNBC.In the last decades, the use of more aggressive chemotherapy has produced a clear improvement of the prognosis in women with TNBC, but this approach results in an unacceptable deterioration in the quality of life, also if some support therapies try to relieve patients from distress. In addition, there is the general belief that it is impossible to further improve the prognosis of TNBC patients with chemotherapy alone. In view of that, there is a feverish search for new “clever drugs” able both to rescue chemo-resistant, and to reduce the burden of chemotherapy in chemo-responsive TNBC patients.A major obstacle to identifying actionable targets in TNBC is the vast disease heterogeneity both inter-tumour and intra-tumour and years of study have failed to demonstrate a single unifying alteration that is targetable in TNBC. TNBC is considered the subtype that best benefits from the neoadjuvant model, since the strong correlation between pathological Complete Response and long-term Disease-Free-Survival in these patients.In this review, we discuss the recent discoveries that have furthered our understanding of TNBC, with a focus on the subtyping of TNBC. We also explore the implications of these discoveries for future treatments and highlight the need for a completely different type of clinical trials.     

Overweight in singletons compared to children with siblings: the IDEFICS study

The aim of this study was to compare the prevalence of overweight in only children to those with siblings and to explore potential behavioral mediating factors. This study relies upon cross-sectional data collected at survey centers in eight European countries participating in Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS (IDEFICS). The present analysis is based on measured anthropometry and parent or guardian-reported socio-demographic characteristics. Subjects include 12 720 children aged 2–9 years for whom number of siblings was known. Singletons were more likely (odds ratio 1.52, 95% confidence interval (CI):1.34–1.72) to be overweight than their peers with siblings when controlling for factors related to childhood overweight, including survey country, parental education, parental weight, maternal age, child''s age, birth weight and gender. The three southernmost countries have over threefold risk of overweight, dominated by Italy, compared with the north-central countries, which is not explained by the prevalence of singleton children. The excess risk of overweight among children without siblings was robustly observed even when considering behavioral mediating factors (playtime, screen time per day, dietary propensities for sugar or fat, parental attitudes towards food rewards and television in the child''s bedroom). Among singletons aged 6–9 years, the excess risk of overweight was 1.70 (95% CI: 1.44–2.01) compared with 1.32 (95% CI: 1.10–1.60) in younger singletons.     

Activation of human platelets by immune complexes prepared with cationized human IgG

The present study shows that the ability of soluble immune complexes (IC), prepared with human IgG and rabbit IgG antibodies against human IgG, to trigger platelet activation was markedly higher for IC prepared with cationized human IgG (catIC) compared with those prepared with untreated human IgG (cIC). CatIC induced platelet aggregation and adenosine triphosphate release in washed platelets (WP), gel-filtered platelets (GFP), or platelet-rich plasma (PRP) at physiologic concentrations of platelets (3 x 10(8)/mL) and at low concentrations of catIC (1 to 30 micrograms/mL). On the contrary, under similar experimental conditions, cIC did not induce aggregation in PRP, WP, or GFP. Low aggregation responses were only observed using high concentrations of both WP (9 x 10(8)/mL) and cIC (500 micrograms/mL). Interestingly, catIC were also able to induce platelet activation under nonaggregating conditions, as evidenced by P-selectin expression. Cationized human IgG alone did not induce platelet aggregation in PRP but triggered either WP or GFP aggregation. However, the concentration needed to induce these responses, was about eightfold higher than those required for catIC. The responses induced either by catIC or cationized human IgG were completely inhibited by treatment with heparin, dextran sulphate, EDTA, prostaglandin E1, or IV3, a monoclonal antibody against the receptor II for the Fc portion of IgG (Fc gamma RII). The data presented in this study suggest that IgG charge constitutes a critical property that conditions the ability of IC to trigger platelet activation.