Incidence and risk factors of bacterial sepsis and invasive fungal infection in neonates and infants requiring major surgery: an Italian multicentre prospective study.

BACKGROUND: Limited data are currently available on the incidence rates and risk factors for bacterial sepsis and invasive fungal infections (IFIs) among neonates and infants undergoing major surgery. AIM: To assess the incidence of bacterial sepsis and IFI, fungal colonization, risk factors for sepsis, and mortality in neonates and infants aged <3 months undergoing major surgery. METHODS: A multicentre prospective study was conducted involving 13 level-3 neonatal intensive care units in Italy, enrolling all infants aged ≤3 months undergoing major surgery. FINDINGS: From 2018 to 2021, 541 patients were enrolled. During hospitalization, 248 patients had a bacterial infection, and 23 patients had a fungal infection. Eighty-four patients were colonized by fungal strains. Overall, in-hospital mortality was 2.8%, but this was higher in infected than in uninfected infants (P = 0.034). In multivariate analysis, antibiotic exposure before surgery, ultrasound-guided or surgical placement of vascular catheters, vascular catheterization duration, and gestational age ≤28 weeks were all associated with bacterial sepsis. The risk of IFI was markedly higher in colonized infants (odds ratio (OR): 8.20; P < 0.001) and was linearly associated with the duration of vascular catheterization. Fungal colonization in infants with abdominal surgery increased the probability of IFI 11-fold (OR: 11.1; P < 0.001). CONCLUSION: Preventive strategies such as early removal of vascular catheters and the fluconazole prophylaxis should be considered to prevent bacterial and fungal sepsis in infants undergoing abdominal surgery, and even more so in those with fungal colonization.

Multiplex SNP genotyping in whole blood using an integrated microfluidic lab-on-a-chip.

Pharmacogenetics has often been touted as a cornerstone for precision medicine as detailed knowledge of a specific genetic makeup may allow for accurate predictions of a patient's individual drug response. Still, the widespread use of genetic tests is limited as they remain expensive and cumbersome, requiring sophisticated tools and highly trained personnel. In order for pharmacogenetics to reach its full potential, more cost-effective and easily accessible genotyping methods are desired. To meet these challenges, we present a silicon-based integrated microsystem for the detection of multiple single nucleotide polymorphisms (SNPs) directly from human blood. The device combines a blood lysis chamber, a cross-flow filter, a T-junction mixer, and a microreactor for quantitative polymerase chain reaction (qPCR). Using this device, successful on-chip genotyping of two clinically relevant SNPs in human CYP2C9 gene was demonstrated with TaqMan assays, starting from blood. The two SNPs were detected simultaneously by introducing a sequence of plugs, each containing a different set of primers and probes. The method can be easily extended to detect several SNPs. The microsystem described here offers a rapid, reproducible, and accurate sample-to-answer technology enabling multiplex SNP profiling in point-of-care settings, bringing pharmacogenetics-based precision medicine a step closer to reality.

A fish perspective: detecting flow features while moving using an artificial lateral line in steady and unsteady flow.

For underwater vehicles to successfully detect and navigate turbulent flows, sensing the fluid interactions that occur is required. Fish possess a unique sensory organ called the lateral line. Sensory units called neuromasts are distributed over their body, and provide fish with flow-related information. In this study, a three-dimensional fish-shaped head, instrumented with pressure sensors, was used to investigate the pressure signals for relevant hydrodynamic stimuli to an artificial lateral line system. Unsteady wakes were sensed with the objective to detect the edges of the hydrodynamic trail and then explore and characterize the periodicity of the vorticity. The investigated wakes (Kármán vortex streets) were formed behind a range of cylinder diameter sizes (2.5, 4.5 and 10 cm) and flow velocities (9.9, 19.6 and 26.1 cm s(-1)). Results highlight that moving in the flow is advantageous to characterize the flow environment when compared with static analysis. The pressure difference from foremost to side sensors in the frontal plane provides us a useful measure of transition from steady to unsteady flow. The vortex shedding frequency (VSF) and its magnitude can be used to differentiate the source size and flow speed. Moreover, the distribution of the sensing array vertically as well as the laterally allows the Kármán vortex paired vortices to be detected in the pressure signal as twice the VSF.

Propranolol concentrations after oral administration in term and preterm neonates.

OBJECTIVE: While propranolol pharmacokinetics has been extensively studied in adults, this study reports the first evaluation of propranolol pharmacokinetics in term and preterm neonates. METHODS: Propranolol concentrations were measured in four term and 32 preterm newborns treated with oral propranolol at the dose of 0.5 or 0.25 mg/kg every 6 h by serial dried blood spots. RESULTS: The levels of propranolol, although with high inter-individual variability, were proportional with the administered dose. Pharmacokinetic parameters evaluated at the steady state in newborns treated with 0.5 mg/kg/6 h showed values of maximal (71.7 ± 29.8 ng/mL), minimal (42.2 ± 20.8 ng/mL) and average concentration (60.8 ± 25.0 ng/mL), time of maximal concentration (2.6 ± 0.9 h) and area under the time-concentration curve (364.7 ± 150.2 ng/mL/h) similar to those observed in adults. In both dosing groups, elimination half-life was significantly longer (14.9 ± 4.3 and 15.9 ± 6.1 h), and apparent total body clearance (27.2 ± 13.9 and 31.3 ± 13.3 mL/kg/min) lower than those reported in adults, suggesting a slower metabolism in newborns. No differences were observed between newborns with different gestational age or different sex. CONCLUSIONS: Neonates treated with propranolol-exhibited drug concentrations proportional with the dose, with significant long half-life.

Applicability of a new robotic walking aid in a patient with cerebral palsy. Case report.

BACKGROUND: Gait training with the help of assistive technological devices is an innovative field of research in neurological rehabilitation. Most of the available gait training devices do not allow free movement in the environment, which would be the most suitable natural and motivating condition for training children with neurological gait impairment. AIM: To evaluate the potential applicability of a new robotic walking aid as a tool for gait training in non-ambulatory children with Cerebral Palsy. DESIGN: Single case study SETTING: Outpatient regimen POPULATION: A 11-years-old child unable to stand and walk independently as a result of spastic tetraplegic cerebral palsy (CP). METHODS: The experimental device was a newly actuated version of a dynamic combined walking and standing aid (NF-Walker®) available in the market which was modified by means of two pneumatic artificial muscles driven by a foot-switch inserted in the shoes. The child was tested at baseline (while maintaining the standing position aided by the non-actuated NF-Walker®) and in the experimental condition (while using the actuated robotic aid). The outcome measures were: 2-minute walking test, 10-metre walking test, respiratory and heart parameters, energy cost of locomotion. RESULTS: At baseline, the child was unable to perform any autonomous form of locomotion. When assisted by the actuated aid (i.e. during the experimental condition), the child was successful in moving around in his environment. His performance was 19.63 m in the 2-minute walking test and 64 s in the 10-metre walking test. Respiratory and heart parameters were higher than healthy age-matched children both at baseline and in the experimental condition. The energy cost of gait, which was not valuable in the baseline condition, was significantly higher than normality during the experimental condition. CONCLUSION: The new robotic walking aid may help children suffering from CP with severe impairment of gait to move around in their environment. CLINICAL REHABILITATION IMPACT: This new robotic walking device may have a potential impact in stimulating the development and in training of gait in children with neurological gait impairment. Future studies are warranted in order to test this hypothesis.

Amniotic band syndrome: a case report.

Amniotic band syndrome is an uncommon congenital pathological condition that may lead to malformations and foetal-infant death. We report an autoptic case. The patient was a male preterm infant. At 14 weeks of gestation, a routine ultrasonography showed severe craniofacial anomalies and a close contiguity of the foetal head with the amnios. The neonate survived three days, after which an autopsy was carried out. The infant had a frontoparietal meningoencephalocele; a fibrous band was attached to the skin, close to the meningoencephalocele base. Cleft lip and palate, nose deformation and agenesis of the right eye were also present. At the opening of the cranial cavity, occipital hyperostosis was observed. The herniated brain showed anatomical abnormalities that made identification of normal structures difficult. Microscopically, the nervous parenchyma had architectural disorganization and immaturity, and the fibrous band consisted of amniotic membranes. As evident from this case report, amniotic band syndrome may cause severe malformations and foetal-infant death.

Persistent pulmonary hypertension of the newborn refractory to inhaled nitric oxide and prostacyclin, responsive to neuromuscular blockade.

Neonatal pulmonary hypertension refractory to high frequency ventilation (HFOV) and inhaled nitric oxide (iNO) is an occasional occurrence. We report a full-term neonate with severe pulmonary hypertension unresponsive to the treatment with HFOV and iNO, later associated with prostacyclin, who rapidly improved after the addition of vecuronium, a neuromuscular blocker.

Integrated fluidic system for bio-molecule separation.

An integrated fluidic system has been fabricated, capable of separating a mixture of different bio-molecules into its components. It is composed of a filter and an actuator; the pressure generated by the actuator sustains the flow of the mixture through the filter. The actuator is made by stacking several layers of conductive polymer. Actuator strain in excess of 10% has been obtained, which corresponds to a fluid flow of 3 microL/min in the fabricated system. The filter consists of an ordered array of Si micro-pillars. A mixture composed of DNA fragments of different length (300 and 400 base-pair) has been effectively separated by using the fabricated filter and chromatographic techniques.

Insulin-resistant hyperglycaemia complicating neonatal onset of methylmalonic and propionic acidaemias.

BACKGROUND: Insulin-resistant hyperglycaemia may occasionally complicate the clinical course of organic acidaemias. STUDY DESIGN: Clinical observation. RESULTS: Two term infants, one suffering from acute early-onset methylmalonic acidaemia, the other suffering from acute early-onset propionic acidaemia, presented acutely with dehydration, ketoacidosis, and hyperammonaemia. Urinary organic acid, plasma amino acids, and blood and plasma acylcarnitine analysis allowed the diagnosis of methylmalonic and propionic acidaemias. The detection of the novel c.481G>A (p.Gly161Arg) and the known c.655A>T (p.Asn219Tyr) MUT gene mutations identified the first patient as affected by methylmalonic acidaemia mut type. The high increase of propionylcarnitine after carnitine administration in both patients suggested a greatly elevated metabolic intoxication. Both newborns showed insulin-resistant hyperglycaemia. Patient 1 died, but patient 2, after a strong reduction of glucose administration, survived. To our knowledge, this is the only patient with this complication who survived. CONCLUSION: Insulin-resistant hyperglycaemia complicating neonatal onset of methylmalonic and propionic acidaemias is probably a marker of a serious disease. One patient with this complication survived after a strong reduction of glucose administration. Even if this is probably only a partial intervention, we hypothesize that in this situation a reduction of glucose administration can reduce almost the risk of persistent hyperglycaemia. Further studies are required to confirm our hypothesis.

Congenital microgastria and primary ciliary dyskinesia in a newborn with DiGeorge syndrome and 22q11.2 deletion.

BACKGROUND: Congenital microgastria is an uncommon result of impairment of normal foregut development and rotation during early embryology. Only about 50 cases have been reported in the literature, mostly associated with other multiple congenital anomalies. CASE REPORT: The case of a female newborn with multiple abnormalities, including cardiovascular malformation (type I truncus arteriosus communis) with deletion of chromosome 22q11.2, severe immunodeficiency (DiGeorge syndrome), microgastria, and impaired mucociliary function (primary ciliary dyskinesia) is reported. CONCLUSIONS: An association between the deletion of chromosome 22q11.2, microgastria, and impaired mucociliary function has never been observed before. A casual association seems highly unlikely and we can not exclude the possibility of genetic mechanisms that may link those syndromes.

[Esophageal atresia with distal tracheo-esophageal fistula. Evolution of the treatment in the period of 1955-2000 at the Anna Meyer Children's Hospital of Florence]. / Atresia dell'esofago con fistola esofago-tracheale distale. Evoluzione del trattamento nel periodo 1955-2000 nell'Ospedale Pediatrico Anna Meyer di Firenze.

BACKGROUND: Over the past decades the esophageal atresia (EA) has represented the greatest challenging malformation encountered by the pediatric surgeon. Since then, there have been considerable advancements in the treatment of EA. In this paper the experience at the "Anna Meyer Children's Hospital of Florence" in regards to the surgical treatment of the EA from 1955 to present day is reported, so that the analysis of the various medical and surgical choices followed by the authors and their predecessors in this long period, can be an important learning tool for the EA management. METHODS: From 1955 to 2000, 223 newborns affected by EA with tracheoesophageal fistula (TEF) have been operated on out of a total of 250 cases of EA. Our experience has been subdivided into periods on the basis of homogeneous medical and surgical treatment adopted in that determined time. We have analyzed particularly the data of the last period 1995-2000, where there has been a well standardized protocol of treatment from the medical, surgical and intensive care points of view. RESULTS: The mortality rate has decreased from 44.8 to 3.4% with a significant reduction (p<0.001) between the years 1979-1983 and 1984-2000, due to the introduction of a perioperative treatment in the newborn intensive care unit. Moreover, a significant correlation (p<0.05) has been shown between low birthweight and associated malformations, two risk factors that however do not negatively influence the results of the treatment in the last period 1995-2000. CONCLUSIONS: A full integration between the surgeon and neonatologist is necessary in order to guarantee a good result. The risk connected to EA is not as much the surgical procedure as the presence or absence of associate malformations that are undetected in the prenatal diagnosis. It is suggested that, in order to further reduce the mortality and morbidity rate after EA correction, the number of prenatal diagnoses should be increased.

Failure of early dextromethorphan and sodium benzoate therapy in an infant with nonketotic hyperglycinemia.

We report an infant with neonatal nonketotic hyperglycinemia (NKH), diagnosed early and treated with dextromethorphan (DM) and sodium benzoate therapy from the 65th hour of life. Initially the patient responded to treatment showing clinical and electroencephalographic improvement: myoclonic jerks disappeared, muscular tone, reactivity to stimuli and spontaneous movements increased, assisted ventilation was no longer necessary and bottle feeding was initiated successfully; on EEG the suppression-burst pattern disappeared and the background activity was well-organized. At three months of age he developed flexor spasms and hypsarrhythmia. In spite of increasing doses of DM as high as 40 mg/kg/day and persistent therapy with sodium benzoate the child progressively deteriorated and died at the age of 5 months and 7 days. We stress that the adverse clinical course occurred in our patient even though DM and sodium benzoate therapy was started much earlier than in other reported cases. It is possible that prenatal brain damage and probable genetic variants (i.e. absent or minimal residual enzymatic activity and interindividual variations in DM metabolism) affect the response to therapy.

[Usefulness of pulsed doppler echocardiography in the diagnosis and medical therapy of patent ductus arteriosus in the newborn with respiratory distress]. / Utilità dell'ecocardiografia doppler pulsato nella diagnosi e terapia medica del dotto arterioso pervio del neonato con distress respiratorio.

In preterm infants patent ductus arteriosus (PDA) may worsen the clinical course of Respiratory Distress Syndrome (RDS). Indomethacin is usually effective in producing duct closure in the first days of life, but clinical diagnosis is often difficult to perform in these patients. In recent years Pulsed Doppler Cross-Sectional Echocardiography (PD-CSE) has made it possible to identify the duct and to assess noninvasively the characteristics of blood flow within it. The aim of this study was to verify the utility of PD-CSE in the early diagnosis of PDA and to provide the basis for a more effective drug therapy. Among 51 patients with RDS, a significant PDA was evidenced in 20 with PD-CSE and in only 8/20 with physical and E-TM examination (p less than 0.01). Indomethacin administration produced duct closure in 19/20 patients (95%). In this study PD-CSE has been more sensitive than the other noninvasive procedures in the diagnosis of PDA; moreover, the success with drug therapy demonstrates the utility of this procedure in providing the basis of a more effective treatment of the duct.

Phenotypic characters related to skin type and minimal erythemal dose.

Minimal erythemal dose (MED) was determined in 155 healthy Caucasoid subjects. Hair color, eye color, number of freckles, and history of sun reactivity and tanning ability, according to the system proposed by Fitzpatrick, were also recorded. In the subjects with skin type I, the values of MED were relatively homogeneous, whereas in subjects with skin types II, III and IV there was a wide variation of MED values. In spite of this variation, a good correlation was found between MED and skin types. MED was found to correlate with hair color, eye color and number of freckles only for some variants of these characters. Low values of MED correlated significantly with red hair, blue eyes and highly freckled skin. Between other variants of the same characters, MED values did not differ significantly. This means that phenotypic characters suggest low MED values only in individuals with red hair, blue eyes and many freckles. In these subjects the phenotypic characters studied may be considered indicative of cancer risk. For all other Caucasoid people the phenotypic characters studied are not predictive of MED nor, probably, of cancer risk.