Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole.

Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic approach using dried blood spots (DBS) to evaluate a population pharmacokinetic model of metronidazole in critically ill preterm infants of gestational age (GA) ≤31 weeks from the Metronidazole Pharmacokinetics in Premature Infants (PTN_METRO, NCT01222585) study. First, we used linear correlation to compare 42 paired DBS and plasma metronidazole concentrations from 21 preterm infants [mean (SD): post natal age 28.0 (21.7) days, GA 26.3 (2.4) weeks]. Using the resulting predictive equation, we estimated plasma metronidazole concentrations (ePlasma) from 399 DBS collected from 122 preterm and term infants [mean (SD): post natal age 16.7 (15.8) days, GA 31.4 (5.1) weeks] from the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections (SCAMP, NCT01994993) trial. When evaluating the PTN_METRO model using ePlasma from the SCAMP trial, we found that the model generally predicted ePlasma well in preterm infants with GA ≤31 weeks. When including ePlasma from term and preterm infants with GA >31 weeks, the model was optimized using a sigmoidal Emax maturation function of postmenstrual age on clearance and estimated the exponent of weight on volume of distribution. The optimized model supports existing dosing guidelines and adds new data to support a 6-hour dosing interval for infants with postmenstrual age >40 weeks. Using an opportunistic DBS to externally validate and optimize a metronidazole population pharmacokinetic model was feasible and useful in this vulnerable population.

Total and segmental phase angle in a cohort of hospitalised patients with COVID-19: mortality prediction and changes throughout hospitalisation.

Body composition and phase angle (PhA) have been used to predict mortality in multiple diseases. However, little has been studied regarding segmental measurements, which could potentially help assess subtle changes in specific tissue segments. This study aimed to identify the total PhA cut-off point associated with mortality risk and changes in body composition within a week of hospitalisation in non-critical hospitalised patients with COVID-19. A cohort study was conducted where patients underwent to a complete nutritional assessment upon admission and after seven days, and followed up until hospital discharge or death. A receiver operating characteristic curve was constructed to determine the PhA cut-off point, and the Kaplan­Meier estimator was used to determine survival analysis. Segmental and complete body compositions on admission and after 7 d were compared. We included 110 patients (60 men) with a mean age of 50·5 ± 15·0 years and a median BMI of 28·5 (IQR, 25·6­33·5) kg/m2. The median length of hospital stay was 6 (IQR, 4­9) d, and the mortality rate was 13·6 %. The PhA cut-off point obtained was 4°, with significant differences in the survival rate (P < 0·001) and mortality (HR = 5·81, 95 % CI: 1·80, 18·67, P = 0·003). Segmental and whole-body compositions were negatively affected within one week of hospitalisation, with changes in the approach by the graphical method in both sexes. Nutritional status deteriorates within a week of hospitalisation. PhA < 4° is strongly associated with increased mortality in non-critical hospitalised patients with COVID-19.

Unintended Consequences of the Neonatal Intensive Care Unit Environment: Integrative Review of Single-Family Room Unit Design.

BACKGROUND: Recent trends in neonatal intensive care unit design have been directed toward reducing negative stimuli and creating a more developmentally appropriate environment for infants who require intensive care. These efforts have included reconfiguring units to provide private rooms for infants. PURPOSE: The purpose of this integrative review was to synthesize and critically analyze negative outcomes for patients, families, and staff who have been identified in the literature related to single-family room (SFR) care in the neonatal intensive care unit. METHODS/SEARCH STRATEGY: The electronic databases of CINAHL, ProQuest Nursing & Allied Health, and PubMed databases were utilized. Inclusion criteria were research studies in English, conducted from 2011 to 2021, in which the focus of the study was related to unit design (SFRs). Based on the inclusion criteria, our search yielded 202 articles, with an additional 2 articles found through reference list searches. After screening, 44 articles met our full inclusion/exclusion criteria. These studies were examined for outcomes related to SFR unit design. FINDINGS/RESULTS: Our findings revealed both positive and negative outcomes related to SFR unit design when compared with traditional open bay units. These outcomes were grouped into 4 domains: Environmental Outcomes, Infant Outcomes, Parent Outcomes, and Staff Outcomes. IMPLICATIONS FOR PRACTICE AND RESEARCH: Although SFR neonatal intensive care unit design improves some outcomes for infants, families, and staff, some unexpected outcomes have been identified. Although these do not negate the positive outcomes, they should be recognized so that steps can be taken to address potential issues and prevent undesired outcomes.

Dosing and Safety of Off-label Use of Caffeine Citrate in Premature Infants.

OBJECTIVE: To characterize the dosing and safety of off-label caffeine citrate in a contemporary cohort of extremely premature infants. STUDY DESIGN: We used electronic health records (2010-2013) from 4 neonatal intensive care units to identify infants of ≤28 weeks of gestational age exposed to caffeine citrate. Safety outcomes included death, bronchopulmonary dysplasia, necrotizing enterocolitis, spontaneous intestinal perforation, intraventricular hemorrhage, patent ductus arteriosus ligation, seizures, and arrhythmias. We used multivariable logistic regression to evaluate the association of caffeine citrate exposure with clinical events. RESULTS: Of 410 infants with a median (IQR) gestational age of 26 (24-27) weeks, 95% received caffeine citrate for >0 days. Infants received a median (IQR) daily dose of 8 (5-10) mg/kg/day. Incidences of clinical events on day of caffeine citrate exposure were death 2%, patent ductus arteriosus ligation 12%, and medical and surgical necrotizing enterocolitis 5% and 4%, respectively. Bronchopulmonary dysplasia occurred in 37% of infants and was not associated with caffeine dose. Increased caffeine citrate dose was associated with lower odds of patent ductus arteriosus ligation and necrotizing enterocolitis. CONCLUSIONS: Caffeine citrate was used in extremely premature infants at younger gestation, at higher doses, and for longer durations than recommended on the drug label. Increased caffeine citrate exposure, dose, or therapy duration was not associated with increased risk of necrotizing enterocolitis.

Prospective observational study of early respiratory management in preterm neonates less than 35 weeks of gestation.

BACKGROUND: Current guidelines for management of respiratory distress syndrome (RDS) recommend continuous positive airway pressure (CPAP) as the primary mode of respiratory support even in the most premature neonates, reserving endotracheal intubation (ETI) for rescue surfactant or respiratory failure. The incidence and timing of ETI in practice is poorly documented. METHODS: In 27 Level III NICUs in the US (n = 19), Canada (n = 3) and Poland (n = 5), demographics and baseline characteristics, respiratory support modalities including timing of ETI, administration of surfactant and caffeine/other methylxanthines, and neonatal morbidities were prospectively recorded in consecutive preterm neonates following written parental consent. Infants were divided into three groups according to gestational age (GA) at birth, namely 26-28, 29-32 and 33-34 weeks. Statistical comparisons between groups were done using Chi-Square tests. RESULTS: Of 2093 neonates (US = 1507, 254 Canada, 332 Poland), 378 (18%) were 26-28 weeks gestational age (GA), 835 (40%) were 29-32 weeks, and 880 (42%) were 33-34 weeks. Antenatal steroid use was 81% overall, and approximately 89% in neonates ≤32 weeks. RDS incidence and use of ventilatory or supplemental oxygen support were similar across all sites. CPAP was initiated in 43% of all infants, being highest in the 29-32-week group, with a lower proportion in other GA categories (p < 0.001). The overall rate of ETI was 74% for neonates 26-28 weeks (42% within 15 min of birth, 49% within 60 min, and 57% within 3 h), 33% for 29-32 weeks (13 16 and 21%, respectively), and 16% for 33-34 weeks (5, 6 and 8%, respectively). Overall intubation rates and timing were similar between countries in all GAs. Rates within each country varied widely, however. Across US sites, overall ETI rates in 26-28-week neonates were 30-60%, and ETI within 15 min varied from 0 to 83%. Similar within 15-min variability was seen at Polish sites (22-67%) in this GA, and within all countries for 29-32 and 33-34-week neonates. CONCLUSION: Despite published guidelines for management of RDS, rate and timing of ETI varies widely, apparently unrelated to severity of illness. The impact of this variability on outcome is unknown but provides opportunities for further approaches which can avoid the need for ETI.

Achieving and maintaining lung volume in the preterm infant: from the first breath to the NICU.

The main goal for the neonatologist is to facilitate the adaptation to extra-uterine life during initial transition, while minimizing lung injury opening and protecting the premature lung from the first breath onwards. An appropriate management from birth should lead to the achievement of an early functional residual capacity (FRC), and the following steps should aim at maintaining an adequate lung volume. To date, different strategies are available to optimize fetal-neonatal transition and promote lung recruitment. New ventilation approaches, such as sustained lung inflation (SLI) and "open lung strategy", well-established ventilation techniques with a more tailored application and less invasive modalities to administer surfactant have been recently introduced in clinical practice with promising results. CONCLUSIONS: given the current status of neonatal care, it seems that lung injury and BPD could be reduced with multiple strategies starting early in the delivery room. Literature underlines the importance of a respiratory tailored management of preterm infants from birth and during the whole NICU stay. What is Known: • Experimental and clinical studies have shown that the transition from fetal to adult type cardiorespiratory circulation needs an adequate lung ventilation. An appropriate management in the delivery room should lead to the achievement of an early FRC, and through the following steps, the neonatologist should aim at maintaining an adequate lung volume. • Literature underlines the importance of a respiratory tailored management of preterm infants during the whole NICU stay to maintain the benefits of a successful postnatal adaption. What is New: • Herewith, we describe the most relevant and recent interventions which can be performed from the delivery room to the NICU stay to guarantee an adequate tradition to postnatal life and an effective cardiorespiratory stability.

Impact of Chronic Glucocorticoid Treatment on Cardiovascular Risk Profile in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Systemic lupus erythematosus is highly associated with premature atherosclerosis and cardiovascular events. The origin of this subclinical atherosclerosis has been attributed mainly to the inflammatory nature of the disease. OBJECTIVE: To assess the effect of long-term use of glucocorticoids on cardiovascular risk in patients with systemic lupus erythematosus. MATERIAL AND METHODS: We conducted a registry-based retrospective cohort study. We determined 2 periods: (1) Time 0, that is, time of diagnosis and (2) time 1, that is, when the study was finalized. At both times, the cardiovascular risk was evaluated using the Framingham scale and their scores were compared. Afterward, the change magnitude between the 2 times was evaluated and associated with the cumulative glucocorticoids dose. RESULTS: One hundred one patients were included. The mean ± SD age was 26.5 ± 5 years. Length of disease evolution was of 7.8 ± 4.9 years. There was an 8-point increase in the Framingham score, from -8.1 ± 4 to 0.8 ± 7; P < 0.0001. The correlation between the magnitude of the increase in Framingham score and their corresponding cumulative dose showed a coefficient of 0.88; P < 0.001. CONCLUSIONS: The glucocorticoids are a primary factor that influences cardiovascular risk. There is a directly proportional relationship between the cumulative glucocorticoid dose and the increase in cardiovascular risk.

Prospective study about the security and efficacy of treatment without antibiotic therapy of patients diagnosed with acute uncomplicated diverticulitis after launching a protocol at a tertiary hospital.

INTRODUCTION: The main objective of our study is to analyze the results in our hospital after launching a treatment protocol without antibiotic therapy for patients diagnosed with acute uncomplicated diverticulitis. METHODS: Our observational, prospective, single-center study was developed after launching a treatment protocol without antibiotic therapy for patients diagnosed with acute uncomplicated diverticulitis (AUD) in January 2021. The follow-up period was from January 1, 2021 to September 30, 2023. Variables evaluated by the study have included demographic and analytical variables, as well as those related to diagnosis and whether the patients needed to start antibiotic treatment, inpatient treatment, or surgical procedures. RESULTS: In total, 199 patients were diagnosed with AUD, 75 of whom were treated without antibiotic therapy as outpatients. Seven of these patients needed to start antibiotic treatment because of adverse evolution; none of these patients required surgical procedures. The need for inpatient treatment, urgent care, or surgical procedures is similar to the group of patients treated with antibiotics. The main risk factor of failure of outpatient treatment without antibiotic therapy identified by the study was the presence of bacteriuria at diagnosis. CONCLUSIONS: Our results confirm previous reports, observing that treatment without antibiotic therapy in selected patients with AUD is safe.

Preterm infant nutrition: considerations for infants at risk of refeeding syndrome.

Refeeding syndrome (RS) in preterm infants is a scenario of fetal malnutrition, primarily resulting from placental insufficiency, followed by a postnatal physiologic adaptation and response to an imbalance of nutrients provided parenterally. Growth restriction and small gestational age status are common findings in infants at risk of developing RS. Adverse clinical outcomes associated with RS may be severe and life-threatening. The biochemical abnormalities that occur in RS may be mitigated through careful monitoring and adaptation of the clinical management of parenteral and enteral nutrition. This perspective reviews the physiology and metabolism in infants with RS and provides suggested approaches to their clinical monitoring and nutritional management.

Contributions of the voluntary local review process to policy integration: evidence from frontrunner cities.

The implementation of the Sustainable Development Goals (SDGs) relies on effective policy integration at all levels of government. However, integration across policy domains remains challenging for local authorities, particularly when it comes to articulating policies that recognise trade-offs and interactions between different SDGs. This study explores how the Voluntary Local Review (VLR) process-a tool to localise the 2030 Agenda-contributes to policy integration by thematically analysing interviews with city officials in 12 frontrunner cities that conducted a VLR between 2019 and 2020. Our results suggest three main ways in which the VLR process affects policy integration: (1) by facilitating cooperation and interdependencies between different policy sectors; (2) by creating new instruments to mainstream SDGs; and (3) by enhancing sustainability competencies. Hence, our study suggests that conducting a VLR has the transformative potential to achieve greater policy integration and further the 2030 Agenda.

A randomized controlled trial of oropharyngeal therapy with mother's own milk for premature infants.

OBJECTIVE: To determine if oropharyngeal therapy with mother's own milk (OPT-MOM) reduces late-onset sepsis (L-OS; primary outcome), NEC, death, length of stay, time to full enteral nutrition (FEN) and full oral feeds in preterm infants (BW < 1250 g). DESIGN: Infants (N = 220) were randomized to Group A (milk) or B (placebo) and received 0.2 mL every 2 h for 48 h, then every 3 h until 32 weeks CGA. RESULTS: There were no significant differences in L-OS, NEC or death. Group A trended towards an 8-day reduction in stay, 8-day reduction in time to FEN and a 6-day reduction in time to full oral feeds, compared to B. While clinically relevant, due to large variability in outcomes and lack of power, p values were > 0.05. CONCLUSION: OPT-MOM did not reduce L-OS, NEC or death. Group A trended towards a reduced stay and better nutritional outcomes, but results were not statistically significant. CLINICALTRIALS: GOV: NCT02116699.

RDS-NExT workshop: consensus statements for the use of surfactant in preterm neonates with RDS.

OBJECTIVE: To provide the best clinical practice guidance for surfactant use in preterm neonates with respiratory distress syndrome (RDS). The RDS-Neonatal Expert Taskforce (RDS-NExT) initiative was intended to add to existing evidence and clinical guidelines, where evidence is lacking, with input from an expert panel. STUDY DESIGN: An expert panel of healthcare providers specializing in neonatal intensive care was convened and administered a survey questionnaire, followed by 3 virtual workshops. A modified Delphi method was used to obtain consensus around topics in surfactant use in neonatal RDS. RESULT: Statements focused on establishing RDS diagnosis and indicators for surfactant administration, surfactant administration methods and techniques, and other considerations. After discussion and voting, consensus was achieved on 20 statements. CONCLUSION: These consensus statements provide practical guidance for surfactant administration in preterm neonates with RDS, with a goal to contribute to improving the care of neonates and providing a stimulus for further investigation to bridge existing knowledge gaps.

A pilot, randomized, controlled clinical trial of lucinactant, a peptide-containing synthetic surfactant, in infants with acute hypoxemic respiratory failure.

OBJECTIVE: Inhibition of surfactant function and abnormal surfactant synthesis lead to surfactant dysfunction in children with acute hypoxemic respiratory failure. We evaluated whether intratracheal lucinactant, a synthetic, peptide-containing surfactant, was safe and well-tolerated in infants with acute hypoxemic respiratory failure, and assessed its effects on clinical outcomes. METHODS AND MAIN RESULTS: Infants ≤ 2 yrs of age with acute hypoxemic respiratory failure were enrolled in a phase II, double-blind, multinational, placebo-controlled randomized trial across 36 pediatric intensive care units. Infants requiring mechanical ventilation with persistent hypoxemia meeting acute lung injury criteria were randomized to receive intratracheal lucinactant (175 mg/kg) or air placebo. One retreatment was allowed 12-24 hrs after initial dosing if hypoxemia persisted. Peri-dosing tolerability of intratracheal lucinactant and adverse experiences were assessed. Mechanical ventilation duration was analyzed using analysis of variance. The Cochran-Mantel-Haenszel test was used for categorical variables.We enrolled 165 infants (84 lucinactant; 81 placebo) with acute hypoxemic respiratory failure. There were no significant differences in baseline subject characteristics, with the exception of a lower positive end-expiratory pressure and higher tidal volume in placebo subjects. The incidence of transient peri-dosing bradycardia and desaturation was significantly higher in the lucinactant treatment group. There were no statistical differences between groups for other adverse events or mortality. Oxygenation improved in infants randomized to receive lucinactant as indicated by fewer second treatments (67% lucinactant vs. 81% placebo, p = .02) and a trend in improvement in partial pressure of oxygen in arterial blood to fraction of inspired oxygen from eligibility to 48 hrs after dose (p = .06). There was no significant reduction in duration of mechanical ventilation with lucinactant (geometric least square means: 4.0 days lucinactant vs. 4.5 days placebo; p = .254). In a subset of infants (n = 22), the duration of mechanical ventilation in children with acute lung injury (partial pressure of oxygen in arterial blood to fraction of inspired oxygen >200) was significantly shorter with lucinactant (least square means: 2.4 days lucinactant vs. 4.3 days placebo; p = .006). CONCLUSIONS: In mechanically ventilated infants with acute hypoxemic respiratory failure, treatment with intratracheal lucinactant appeared to be generally safe. An improvement in oxygenation and a significantly reduced requirement for retreatment suggests that lucinactant might improve lung function in infants with acute hypoxemic respiratory failure.

High mortality at the beginning of the COVID-19 pandemic in a referral center in the metropolitan area of Mexico City.

INTRODUCTION: There is limited information about the coronavirus disease 2019 (COVID-19) disease in Latin-American countries. Our objective was to describe the clinical characteristics and outcomes of COVID-19 patients in Mexico. METHODOLOGY: We conducted a retrospective cohort study with 333 consecutive patients who were admitted to Hospital de Especialidades "Dr. Antonio Fraga Mouret" in Mexico City with COVID-19 between April 1, 2020, and June 30, 2020. Demographic, clinical, laboratory data, treatment details and 30-day outcomes were analyzed. RESULTS: The patients studied included 52% men (172/233) and the median age was 45 years. Up to 75% (250/333) of patients were classified as overweight or obese. There were 185 (56%) inpatients; 85% (158/185) were hospitalized in the general ward, and 15% (27/185) in the Intensive Care Unit (ICU). Laboratory measurements showed significant differences between inpatients and outpatients such as lymphocyte-count (median 0.8 vs 1.2×109/L, p < 0.001), LDH (median 650 vs 294 U/L, p < 0.001), CRP (median 147 vs 5 mg/L, p = 0.007), CK-MB (median, 15 vs 10 U/L, p = 0.008), ferritin (median, 860 vs 392 ng/mL, p = 0.02), and D-dimer (median, 780 vs 600 ng/mL, p = 0.15). These differences were seen between survivor and non-survivor patients as well. The rate of death in mechanically ventilated patients was 94% (67/71). Mortality at 30-day follow-up was 57% (105/185). CONCLUSIONS: We observed that majority of the non-survivors were obese and young. Complications leading to death was observed in majority of the cases.

Systematic Reviews in Neonatal Respiratory Care: Are Some Conclusions Misleading?

An increasing amount of information is currently available in neonatal respiratory care. Systematic reviews are an important tool for clinical decision-making. The challenge is to combine studies that address a specific clinical question and have similar characteristics in terms of populations, interventions, comparators, and outcomes, so that their combined results provide a more precise estimate of the effect that can be validly extrapolated into clinical practice. The concept of heterogeneity is reviewed, emphasizing that it should be considered in a wider perspective and not just as a mere statistical test. A case is made of how well-designed studies of the neonatal respiratory literature, when equivocally combined, can provide very precise but potentially biased results. Systematic reviews in this field and others should be rigorously peer-reviewed before publication to avoid misleading readers to potentially biased conclusions.

Generalized chronic erythema nodosum: to consider Weber-Christian disease. / Eritema nudoso crónico de localización generalizada: a considerar enfermedad de Weber-Christian.

BACKGROUND: Weber-Christian disease is a recurrent, non-suppurative, febrile nodular panniculitis, more frequent in young women. It is characterized by recurrent outbreaks of subcutaneous nodules, distributed symmetrically. It has an idiopathic origin, or it is secondary to pancreatic disease, physicochemical agents or alpha-1 antitrypsin deficiency. It can affect any tissue with body fat. Histologically is a lobular panniculitis without vasculitis. CASE REPORT: 23-year-old woman. She was admitted with subcutaneous painful nodules in pelvic, gluteus and forearms, with erythematous and hyperpigmented plaques; ecchymosis in the right upper eyelid and bilateral hyposphagma; fever of 38 °C; diaphoresis and oral ulcers, not painful. The hemogram showed pancytopenia, elevation of acute phase reagents, amylase and normal lipase. Blood culture was negative. Antinuclear antibodies and complement were normal. Computed tomography of the abdomen showed disseminated hyperdensity in subcutaneous tissue. The biopsy showed lobular panniculitis without vasculitis compatible with WeberChristian panniculitis. The patient was treated with steroids and immunosuppressive therapy. CONCLUSIONS: Infectious etiology and other causes of erythematous nodules were ruled out through clinical evolution and complementary studies. The patient presented spontaneous involution in several weeks and sometimes the lesions evolved to sterile abscesses, in addition to systemic clinical manifestations. Corticosteroid therapy was deemed successful.

INTRODUCCIÓN: La enfermedad de Weber-Christian es una paniculitis nodular recidivante, no supurativa, febril, más frecuente en las mujeres jóvenes. Se caracteriza por brotes recurrentes de nódulos subcutáneos, de distribución simétrica. Tiene un origen idiopático o es secundaria a enfermedad pancreática, agentes fisicoquímicos o déficit de alfa-1-antitripsina. Puede afectar cualquier tejido del organismo que tenga grasa. Histológicamente presenta paniculitis lobulillar sin vasculitis. CASO CLÍNICO: Mujer de 23 años que ingresó por nódulos subcutáneos dolorosos con equimosis en miembros pélvicos, glúteos y antebrazos, con placas eritematosas e hiperpigmentadas; equimosis en párpado superior derecho e hiposfagma bilateral; fiebre de 38 °C; diaforesis y úlceras orales no dolorosas. El hemograma mostró pancitopenia, elevación de los reactantes de fase aguda, y amilasa y lipasa normales. Los cultivos fueron negativos. Los anticuerpos antinucleares y el complemento fueron normales. La tomografía del abdomen presentó hiperdensidad en tejido graso subcutáneo diseminada. La biopsia reveló paniculitis lobulillar sin vasculitis, compatible con paniculitis de Weber-Christian. Se trató con esteroide e inmunosupresor. CONCLUSIONES: Se descartaron la etiología infecciosa y otras causas de nódulo eritematoso por la evolución clínica y los estudios complementarios. La paciente presentó en varias semanas una involución espontánea; en ocasiones, las lesiones evolucionaron a abscesos estériles, además de manifestaciones clínicas sistémicas. El tratamiento corticoideo tuvo buen resultado.

Safety of Metronidazole in Late Pre-term and Term Infants with Complicated Intra-abdominal Infections.

BACKGROUND: Metronidazole is frequently used off-label in infants with complicated intra-abdominal infections (cIAI) to provide coverage against anaerobic organisms, but its safety and efficacy in this indication are unknown. METHODS: In the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections open-label multicenter trial infants ≥34 weeks gestation at birth and <121 days postnatal age with cIAIs were administered metronidazole as part of multimodal therapy. Metronidazole safety was evaluated by reporting of adverse events (AEs) and safety events of special interest. Cure from disease was determined by blood cultures and a clinical cure score >4. A blinded adjudication committee reviewed all safety events of special interest. RESULTS: Fifty-five infants were included, median gestational age was 36 weeks (range: 34-41) and postnatal age was 7 days (0-63). The most common additional antibiotics received included gentamicin, piperacillin-tazobactam, ampicillin and vancomycin. Only one AE, a candidal rash, was identified to be potentially caused by metronidazole administration. One infant died of cardiopulmonary failure, which was deemed unrelated to metronidazole. The most common events of special interest included feeding intolerance in 18 (33%) infants, and exploratory laparotomy in 10 (18%) requiring intestinal anastomosis in 7 (13%) infants. There was 1 (2%) intestinal stricture. Fifty-three infants (96%) achieved overall therapeutic success, 54 (98%) were alive through 30 days post-study therapy, and 54 (98%) had 30-day clinical cure score >4. CONCLUSIONS: In a cohort of late pre-term and term infants with cIAIs, combination antibiotic therapy that included metronidazole was safe, and therapeutic success was high.

Neurons in motion: same principles for different shapes?

The special conformation of the developing nervous system, in which progenitor zones are largely confined to the lumen of the neural tube, places neuronal migration as one of the most fundamental processes in brain development. Previous studies have shown that different neuronal types adopt distinct morphological modes of migration in the developing brain, indicating that neuronal migration might be a diverse process. Here, we review recent data on the molecular mechanisms underlying neuronal migration that suggest that similar signaling principles are responsible for the frequently variable morphology of different types of migrating neuron. According to this idea, the same basic molecular mechanisms found in other cell types, such as fibroblasts, might have been adapted to the special morphological needs of migrating neurons in different regions of the developing brain.

Telencephalon ablation impairs goldfish allocentric spatial learning in a "hole-board" task.

The present work analyzes the involvement of telencephalon of goldfish in spatial strategies, using a procedure analogue to the hole-board task. With this aim, goldfish with sham operation or telencephalon ablation were trained to find a baited feeder within a twenty-five feeder matrix, which maintained stable spatial relationships relative to five peripheral landmarks. After training, different types of probe tests were conducted. Although both groups learned the task, probe trials showed that whereas the sham animals used the whole configuration of cues to implement map-like strategies the telencephalic animals used a guidance strategy based on cues located in the vicinity of the baited feeder. These results confirm the role of teleost fish telencephalon in the use of allocentric strategies obtained with other spatial procedures, and indicate that the hole-board task described here for goldfish is a useful tool to assess the neural bases of spatial cognition in teleost fish.