Standardization of Pediatric Noncardiac Operating Room to Intensive Care Unit Handoffs Improves Communication and Patient Care.

OBJECTIVES: Handoffs are critical points in transitioning care between multidisciplinary teams, yet data regarding intensive care unit (ICU) handoffs in pediatric noncardiac surgical patients are lacking. We hypothesized that standardized handoffs from the pediatric operating room (OR) to the ICU would improve physician presence, communication, and patient care parameters. METHODS: This quality improvement initiative was performed at a tertiary children's hospital. Stakeholders (anesthesiologists, nurses, intensivists, and surgeons) developed a standardized OR to pediatric and neonatal ICU handoff process based on common goals and outcomes of interest. Baseline data were collected before intervention. Implementation was carried out in 2 phases, phase 1 with a written handoff and Phase 2 with a scripted handoff process. Data collected by trained observers included handoff attendance, distractions, and transfer of essential patient information. As a surrogate for outcomes, patient care parameter data were collected for 6 hours after transfer. RESULTS: After phase 1, surgery and ICU physician attendance increased significantly, distractions decreased, and communication of essential patient data improved. In phase 2 (scripted handoff), attendance continued to rise, distractions remained decreased, and transfer of essential information was still improved compared with baseline. Mean handoff duration did not significantly change throughout the study. Certain patient care parameters (escalation of respiratory support, additional laboratory studies, vasopressor administration, antibiotic administration and timing) remained unchanged compared with baseline. However, the need for resuscitative fluid bolus or blood products significantly decreased after implementation phase 2. CONCLUSIONS: Standardized handoffs for pediatric noncardiac surgical patients from the OR to the ICU can improve provider attendance and communication.

Impact of Cardiac Risk Factors in the Postsurgical Outcomes of Patients With Cleft Lip.

ABSTRACT: Congenital cardiac comorbidities represent a potentially elevated risk for complications in patients undergoing cleft lip repair. National databases, such as the National Surgical Quality Improvement Program Pediatric (NSQIP-P) allow for analysis of large national datasets to assess these risks and potential complications. The aim of this study is to assess the risk of complications in patients undergoing cleft lip repair with congenital cardiac co-morbidities using the NSQIP-P.The 2012 to 2014 NSQIP-P databases were queried for patients undergoing cleft lip repair. Data abstracted for analysis included demographic, clinical, and outcomes data. Patients with cleft lip were stratified based on the presence or absence of congenital cardiac comorbidities. Univariate analysis and step-wise, forward logistic regression were performed to compare these groups.Nationally, between 2012 and 2014, 2126 patients underwent cleft lip repair, 227 with cardiac disease, and 1899 without cardiac disease. Weights were similar between the groups at the time of surgery, though patients with cardiac comorbidities were older. Postoperatively, cardiac disease patients were more likely to experience an adverse event. Specifically, they were more likely to experience reintubation, reoperation, longer length of stay, and death. Rates of surgical site infection and dehiscence were not different between the groups.This study demonstrates that cleft lip repair in patients with congenital heart defects is safe. However, patients undergoing cleft lip repair with comorbid congenital cardiac disease were more likely to experience adverse events. Cardiac patients require special preoperative evaluation before repair of their cleft lip, but do not appear to experience worse wound-related outcomes.

Impact of Cardiac Risk Factors in the Postsurgical Outcomes of Patients With Cleft Palate: Analysis of the 2012-2014 NSQIP Database.

OBJECTIVE: To assess the risk of complication in patients undergoing cleft palate repair with congenital cardiac comorbidities in a large, national cohort. DESIGN: Retrospective review. PATIENTS/SETTING: Using the 2012-2014 National Surgical Quality Improvement Program (NSQIP) Pediatric database, patients undergoing cleft palate repair were selected for analysis. Patients with cleft palate repairs were stratified based on the presence or absence congenital cardiac comorbidities. Univariate and stepwise forward logistic regression were conducted. MAIN OUTCOME MEASURES: It is hypothesized that risk of postoperative adverse events in patients with congenital cardiac comorbidities is higher than in patients without cardiac disease. RESULTS: Nationally, between 2012 and 2014, 3240 patients underwent cleft palate repair, 422 (13.0%) with cardiac disease, and 2818 (87.0%) without cardiac disease. Patients with cardiac disease were smaller (10.5 [6.6] kg vs 11.6 [8.6] kg, P < .01) and more likely to be premature (4.6% vs 13.0%, P < .01) compared to those without cardiac disease. Postoperatively, patients with cardiac conditions were more likely to experience an adverse event (8.8% vs 4.2%, P < .01). Specifically, they were more likely to experience reintubation (1.7% vs 0.4%, P < .01), reoperation (2.1% vs 0.6%, P < .01), and longer length of stay (2.7 [7.0] vs 1.6 [2.8] days, P < .01). Rates of surgical site infection and dehiscence were not different. CONCLUSIONS: Cleft palate repair in patients with concurrent congenital cardiac defects is a safe procedure but carries elevated risk in the postoperative period as demonstrated in this analysis of the NSQIP-Pediatric database. Technical risks are equivalent. Additional anesthesia and surgical awareness of these potential complications is essential to minimize perianesthesia risks.

Differential susceptibility and maturation of thymocyte subsets during Salmonella Typhimurium infection: insights on the roles of glucocorticoids and Interferon-gamma.

The thymus is known to atrophy during infections; however, a systematic study of changes in thymocyte subpopulations has not been performed. This aspect was investigated, using multi-color flow cytometry, during oral infection of mice with Salmonella Typhimurium (S. Typhimurium). The major highlights are: First, a block in the developmental pathway of CD4-CD8- double negative (DN) thymocytes is observed. Second, CD4+CD8+ double positive (DP) thymocytes, mainly in the DP1 (CD5loCD3lo) and DP2 (CD5hiCD3int), but not DP3 (CD5intCD3hi), subsets are reduced. Third, single positive (SP) thymocytes are more resistant to depletion but their maturation is delayed, leading to accumulation of CD24hiCD3hi SP. Kinetic studies during infection demonstrated differences in sensitivity of thymic subpopulations: Immature single positive (ISP) > DP1, DP2 > DN3, DN4 > DN2 > CD4+ > CD8+. Upon infection, glucocorticoids (GC), inflammatory cytokines, e.g. Ifnγ, etc are induced, which enhance thymocyte death. Treatment with RU486, the GC receptor antagonist, increases the survival of most thymic subsets during infection. Studies with Ifnγ-/- mice demonstrated that endogenous Ifnγ produced during infection enhances the depletion of DN2-DN4 subsets, promotes the accumulation of DP3 and delays the maturation of SP thymocytes. The implications of these observations on host cellular responses during infections are discussed.

Importance of Amino Acids, Gln-119 and Tyr-376, in the S1 Pocket of Escherichia coli Peptidase N in Determining Substrate Specificity.

Peptidase N (PepN) is a broad specific metallo-peptidase and the sole member of the M1 class encoded by Escherichia coli. Comparative analysis of residues present in the S1 subsite of E. coli PepN with other family members revealed that Tyr-381 is conserved whereas Glu-121, Gln-119 and Tyr-376 are partially conserved. The functional importance of these amino acids was investigated by protein engineering studies. The change in Glu-121 to Gln and Tyr-381 to Phe led to catalytically inactive PepN. At the same time, the change in Gln-119 to His (Q119H) and Tyr-376 to Phe (Y376F) led to alterations in substrate specificity. Kinetic studies revealed that purified PepN variants, Q119H and Y376F, cleaved some substrates (e.g. Arg) similar to wild type PepN. However, these variants displayed lower efficacy with other substrates (e.g. Tyr, AAF and Suc-AAF). Q119H or Y376F, cleave a natural peptide (insulin B chain) and a loosely folded protein (casein) with greatly reduced efficacy. The double mutant, i.e. harboring both Q119H and Y376F, displays greatly reduced catalytic activity with respect to all substrates studied. The in vivo significance was addressed by expressing these variants in ΔpepN during nutritional downshift and high temperature (NDHT) stress. Compared to wild type PepN, the Y376F and Q119H variants display lower intracellular amounts of free N-terminal amino acids and reduction in growth during NDHT stress. Finally, structural modeling, using the crystal structure of E. coli PepN bound to substrates, Arg or Tyr, shed insights into the roles of Q119H and Y376F in determining substrate preferences.

Molecular profiling of sepsis in mice using Fourier Transform Infrared Microspectroscopy.

Sepsis is a life threatening condition resulting from a high burden of infection. It is a major health care problem and associated with inflammation, organ dysfunction and significant mortality. However, proper understanding and delineating the changes that occur during this complex condition remains a challenge. A comparative study involving intra-peritoneal injection of BALB/c mice with Salmonella Typhimurium (infection), lipopolysaccharide (endotoxic shock) or thioglycollate (sterile peritonitis) was performed. The changes in organs and sera were profiled using immunological assays and Fourier Transform Infrared (FTIR) micro-spectroscopy. There is a rapid rise in inflammatory cytokines accompanied with lowering of temperature, respiratory rate and glucose amounts in mice injected with S. Typhimurium or lipopolysaccharide. FTIR identifies distinct changes in liver and sera: decrease in glycogen and protein/lipid ratio and increase in DNA and cholesteryl esters. These changes were distinct from the pattern observed in mice treated with thioglycollate and the differences in the data obtained between the three models are discussed. The combination of FTIR spectroscopy and other biomarkers will be valuable in monitoring molecular changes during sepsis.

Interferon-gamma and nitric oxide synthase 2 mediate the aggregation of resident adherent peritoneal exudate cells: implications for the host response to pathogens.

Interferon-gamma (Ifnγ), a key macrophage activating cytokine, plays pleiotropic roles in host immunity. In this study, the ability of Ifnγ to induce the aggregation of resident mouse adherent peritoneal exudate cells (APECs), consisting primarily of macrophages, was investigated. Cell-cell interactions involve adhesion molecules and, upon addition of Ifnγ, CD11b re-localizes preferentially to the sites of interaction on APECs. A functional role of CD11b in enhancing aggregation is demonstrated using Reopro, a blocking reagent, and siRNA to Cd11b. Studies with NG-methyl-L-arginine (LNMA), an inhibitor of Nitric oxide synthase (Nos), NO donors, e.g., S-nitroso-N-acetyl-DL-penicillamine (SNAP) or Diethylenetriamine/nitric oxide adduct (DETA/NO), and Nos2-/- mice identified Nitric oxide (NO) induced by Ifnγ as a key regulator of aggregation of APECs. Further studies with Nos2-/- APECs revealed that some Ifnγ responses are independent of NO: induction of MHC class II and CD80. On the other hand, Nos2 derived NO is important for other functions: motility, phagocytosis, morphology and aggregation. Studies with cytoskeleton depolymerizing agents revealed that Ifnγ and NO mediate the cortical stabilization of Actin and Tubulin which contribute to aggregation of APECs. The biological relevance of aggregation of APECs was delineated using infection experiments with Salmonella Typhimurium (S. Typhimurium). APECs from orally infected, but not uninfected, mice produce high amounts of NO and aggregate upon ex vivo culture in a Nos2-dependent manner. Importantly, aggregated APECs induced by Ifnγ contain fewer intracellular S. Typhimurium compared to their single counterparts post infection. Further experiments with LNMA or Reopro revealed that both NO and CD11b are important for aggregation; in addition, NO is bactericidal. Overall, this study elucidates novel roles for Ifnγ and Nos2 in regulating Actin, Tubulin, CD11b, motility and morphology during the aggregation response of APECs. The implications of aggregation or "group behavior" of APECs are discussed in the context of host resistance to infectious organisms.

Brain-derived neurotrophic factor in infants <32 weeks gestational age: correlation with antenatal factors and postnatal outcomes.

Neurotrophins (NTs) play important roles in brain growth and development. Cord blood (CB) brain-derived neurotrophic factor (BDNF) concentrations increase with gestational age but data regarding postnatal changes are limited. We measured BDNF concentrations after birth in 33 preterm infants <32-wk gestation. Serum was collected at birth (CB), at day 2, between day 6 and 10 (D6), at day 30 (D30), and at day 60 (D60). BDNF concentrations fell on D2 (p = 0.03), recovered by D6 (p = 0.10), and continued to rise thereafter at D30 (p = 0.06) and D60 (p = 0.01) compared with CB. CB BDNF concentrations positively correlated with duration of rupture of membranes (r = 0.43, p = 0.04). Antenatal steroids (ANS, p = 0.02), postnatal steroids (PNS, p = 0.04), and retinopathy of prematurity (ROP, p = 0.02) were identified as significant factors in multivariate analyses. The median (25-75th interquartile range) CB BDNF concentrations were higher in infants who received a complete course ANS compared with those who received a partial course [1461 (553-2064) versus 281 (171-536) pg/mL, p = 0.04]. BDNF concentrations negatively correlated with the use of PNS at D30 (r = -0.53, p = 0.002) and at D60 (r = -0.55, p = 0.009). PNS use was associated with reduced concentrations of BDNF at D30 [733 (101-1983) versus 2224 (1677- 4400) pg/mL, p = 0.004] and at D60 [1149 (288-2270) versus 2560 (1337-5166) pg/mL, p = 0.01]. BDNF concentrations on D60 in infants who developed ROP (n = 16) were lower than those who did not develop ROP (n = 7) [1417 (553-2540) versus 3593 (2620-7433) pg/mL, respectively, p = 0.005]. Our data suggests that BDNF concentrations rise beyond the first week of age. BDNF concentrations correlate with factors that influence neurodevelopment outcomes.

An unusual case of severe therapy-resistant hypertension in a newborn.

Hypertension can occur in up to 2% of neonates, and the spectrum of potential causes is broad. Prompt and thorough evaluation with a main focus on kidney disease is key for appropriate therapy. Here we describe a 2-day-old neonate with feeding intolerance and elevated blood pressure readings. Within 24 hours after birth, the infant's blood pressure increased significantly, with sustained mean arterial pressure >85. Renal Doppler ultrasound showed decreased venous blood flow in the right kidney with an abnormal Doppler wave form suggestive of unilateral renal venous thrombosis. Despite aggressive antihypertensive therapy including hydralazine and enalaprilat, hypertension remained sustained. On day-of-life 4, the infant developed clinical signs of hypertensive encephalopathy and significant cardiac dysfunction. A renal angiography showed complete, likely thrombotic occlusion of the right renal artery. Renal MAG3 imaging showed minimal function of the affected kidney, and a nephrectomy secondary to medically uncontrollable hypertension and worsening cardiac dysfunction was performed. The child is developing normally in all aspects on follow-up evaluations at 6 months and 1 year of age. Reevaluation of the working diagnosis in neonates with hypertension can be necessary to optimize the outcome. The overall prognosis can be excellent even in newborns with profound cardiac and neurologic involvement.