Continuous glucose monitoring profile during therapeutic hypothermia in encephalopathic infants with unfavorable outcome.

BACKGROUND: The relation between glucose homeostasis and outcome in hypoxic-ischemic encephalopathy (HIE) is unclear. To investigate whether glucose abnormalities assessed by using continuous interstitial glucose monitoring (CGM) correlate with later neurological outcomes in HIE. METHODS: Prospective cohort study recruiting full-term neonates who received therapeutic hypothermia for HIE. CGM devices were placed soon after birth and recorded glucose profile for 3 days. The association between hypoglycemia (≤50 mg/dL), hyperglycemia (>144 mg/dL) and primary outcome defined as death or moderate or severe disability was examined with generalized estimating equations adjusted for Apgar scores, umbilical artery pH and base deficit. Neurodevelopmental outcome was assessed between 18 and 24 months. RESULTS: Fifty-four neonates had outcome data available for the analysis; 19 of them (35%) had adverse outcome. Longer duration of hypoglycemia (OR 7.1, 95% CI 1.8-20.3, P < 0.001) and hyperglycemia (OR 5.4, 95% CI 1.6-15.7, P < 0.001), a greater area under the hypoglycemic (OR 2.6, 95% CI 1.4-4.6, P = 0.04) and hyperglycemic (OR 6.4, 95% CI 1.9-16.3, P < 0.001) curve were significantly associated with adverse outcomes. CONCLUSION: Both hyper and hypoglycemia may be associated with adverse outcome in neonates with HIE. Future studies are needed to assess their prognostic association with neurological outcome. IMPACT: Glucose abnormalities during therapeutic hypothermia are associated with later neurological outcomes.Increased glucose variability correlates to the neurological outcome between 18 and 24 months.This study provides the first data on the continuous glucose profile in a group of HIE infants followed up to 2 years of age.Glucose homeostasis represents a key point in the management of HIE patients.Further research is needed to find the appropriate glycemic target in this population.

Long-term improvement in cardiac magnetic resonance in ß-thalassemia major patients treated with deferasirox extends to patients with abnormal baseline cardiac function.

The management of iron overload in thalassemia has changed dramatically since the implementation of magnetic resonance imaging, which allows detection of preclinical iron overload and prevention of clinical complications. This study evaluated the effect of deferasirox (DFX), the newest once-daily oral chelator, on cardiac function, iron overload and cardiovascular events over a longer follow up in a "real world" setting. Longitudinal changes in cardiac magnetic resonance T2*, cardiac function parameters and cardiovascular clinical events were assessed in a cohort of 98 TM patients exposed to DFX for a mean of 6.9 years (range 1.8-11.6 years). No cardiac death or incident heart failure occurred. Cardiac T2* significantly increased (+2.6 ± 11.9 msec; P = 0.035) in the whole population, with a significantly greater increase (+11.6 ± 15.5 msec, P = 0.019) in patients with cardiac iron overload (T2* <20 ms). A significant improvement in left-ventricular ejection fraction (LVEF) (from 50.6 ± 6 to 60.2 ± 5; P = 0.001) was observed in 11 (84.6%) out of 13 patients who normalized cardiac function (LVEF >56%). Arrhythmias were the most frequent cardiac adverse event noted but none led to DFX discontinuation. Our data indicate that DFX is effective in maintaining cardiac iron level in the normal range and in improving cardiac iron overload. No heart failure or cardiac death was reported over this longer observation up to 12 years. For the first time, a DFX-induced improvement in LVEF was observed in a subgroup of patients with abnormal cardiac function at baseline, a preliminary observation which deserves further evaluation.

Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with ß-thalassemia major.

Iron overload in ß-thalassemia major (TM) typically results in iron-induced cardiomyopathy, liver disease, and endocrine complications. We examined the incidence and progression of endocrine disorders (hypothyroidism, diabetes, hypoparathyroidism, hypogonadism), growth and pubertal delay, and bone metabolism disease during long-term deferasirox chelation therapy in a real clinical practice setting. We report a multicenter retrospective cohort study of 86 transfusion-dependent patients with TM treated with once daily deferasirox for a median duration of 6.5 years, up to 10 years. No deaths or new cases of hypothyroidism or diabetes occurred. The incidence of new endocrine complications was 7% (P = 0.338, for change of prevalence from baseline to end of study) and included hypogonadism (n = 5) and hypoparathyroidism (n = 1). Among patients with hypothyroidism or diabetes at baseline, no significant change in thyroid parameters or insulin requirements were observed, respectively. Mean lumbar spine bone mineral density increased significantly (P < 0.001) and the number of patients with lumbar spine osteoporosis significantly decreased (P = 0.022) irrespective of bisphosphonate therapy, hormonal replacement therapy, and calcium or vitamin D supplementation. There were no significant differences in the number of pediatric patients below the 5th centile for height between baseline and study completion. Six pregnancies occurred successfully, and four of them were spontaneous without ovarian stimulation. This is the first study evaluating endocrine function during the newest oral chelation therapy with deferasirox. A low rate of new endocrine disorders and a stabilization of those pre-exisisting was observed in a real clinical practice setting.

Systematic application of SICA-PED protocol for central venous catheterization in neonates: A prospective clinical study on 104 cases.

BACKGROUND: Catheterization of central vessels can be associated with early and late, potentially fatal complications. A proactive approach is imperative to reduce the frequency and magnitude of adverse events. Recently, the GAVeCeLT has proposed a protocol called SICA-PED (i.e. Safe Insertion of Central Access in Pediatric patients) and includes seven evidence-based strategies. METHODS: Through a single-center prospective observational study, the authors wanted to consolidate the efficacy and safety of these protocol in newborns. In a series of 104 newborns, the seven steps of the protocol were applied (1) pre-procedural ultrasound study of the RaCeVA veins, (2) correct aseptic technique, (3) ultrasound-guided venipuncture, (4) intraprocedural localization of the tip of the catheter with TTE (ECHO TIP) and (iECG) intracavitary electrocardiogram, (5) reasoned choice of the implant exit site with the RAVESTO Tunneling technique, (6) anchoring without stitches, and (7) exit point protection with the use of glue and transparent semipermeable membrane. The authors have included a further precaution in point (6) the subcutaneous anchoring system has added the counter-fixation of the catheter wings that we will call 6Plus Point. RESULTS: All infants requiring implantation of elective us-guided central venous access were enrolled in the study. None of the 104 implanted central venous catheters experienced early complications (accidental arterial puncture, PNX, primary malposition); rare late complications such as ecchymosis, CRBSI, exit site infection or dislodgement were observed, No catheter-related thrombotic phenomena were observed. The CRBSI catheter-related infection rate was 2.47 × 1000 days catheter cases. CONCLUSION: The results of this prospective study strengthen the feasibility and efficacy of the SICA-Ped Protocol. Demonstrating that the systematic application of the evidence-based seven-step implantation strategy increases the success rate, minimizes early and late complications, which result in increased patient safety.

Bloodstream Infection Due to a VIM-Metallo-ß-Lactamase-Producing Klebsiella pneumoniae Treated with Cefiderocol in a Preterm Newborn.

BACKGROUND: The prevalence of certain multidrug-resistant organisms (MDROs), especially Gram-negative bacteria, is dramatically increasing in patient care settings, including pediatric and neonatal units. However, most of the new drugs available for the treatment of MDROs have not yet been studied in children and newborns. CASE REPORT: We report the clinical case of a preterm neonate, born at 31 weeks gestation + 1 day of age by emergency Cesarean Section (CS), with a bloodstream infection (BSI) due to a Verona integron-borne metallo-ß-lactamase (VIM)-producing Klebsiella pneumoniae. We successfully treated the infection with cefiderocol in an off-label regimen at the following dose: loading dose 60 mg/kg and then 40 mg/kg every 8 h in extended infusion for 9 days. The baby showed a quick clinical and biochemical improvement and tolerated well the treatment. Follow-up blood cultures at 48 h after the start of cefiderocol were negative. CONCLUSIONS: Antimicrobial-resistant pathogens are of increasing concern in neonatal settings. More studies in this unique population are necessary to better describe the pharmacokinetic and pharmacodynamic profile of the new drugs against MDROs, such as cefiderocol, and to define a proper effective dose.

Magnetic Resonance Biomarkers and Neurological Outcome of Infants with Mild Hypoxic-Ischaemic Encephalopathy Who Progress to Moderate Hypoxic-Ischaemic Encephalopathy.

BACKGROUND: There is increasing concern that infants with mild hypoxic-ischaemic encephalopathy (HIE) may develop seizures and progress to moderate HIE beyond the therapeutic window for cooling. OBJECTIVE: The aim of this study was to examine the effect of therapeutic hypothermia on magnetic resonance imaging (MRI) biomarkers and neurological outcomes in infants with mild HIE and seizures within 24 h after birth. METHODS: This study shows an observational cohort study on 366 (near)-term infants with mild HIE and normal amplitude-integrated electroencephalography background. RESULTS: Forty-one infants showed progression (11.2%); 29/41 (70.7%) were cooled. Infants with progression showed cerebral metabolite perturbations and higher white matter injury scores compared to those without in both cooled and non-cooled groups (p = 0.001, p = 0.02). Abnormal outcomes were seen in 5/12 (42%) non-cooled and 7/29 (24%) cooled infants with progression (p = 0.26). CONCLUSIONS: Early biomarkers are needed to identify infants with mild HIE at risk of progression. Mild HIE infants with progression showed a higher incidence of brain injury and abnormal outcomes.

Impact of intrauterine growth restriction on cerebral and renal oxygenation and perfusion during the first 3 days after birth.

Intrauterine growth restriction (IUGR) is associated with a higher incidence of perinatal complications as well as cardiovascular and renal diseases later on. A better insight into the disease mechanisms underlying these sequalae is important in order to identify which IUGR infants are at a higher risk and find strategies to improve their outcome. In this prospective case-control study we examined whether IUGR had any effect on renal and cerebral perfusion and oxygen saturation in term neonates. We integrated near-infrared spectroscopy (NIRS), echocardiographic, Doppler and renal function data of 105 IUGR infants and 105 age/gender-matched controls. Cerebral and renal regional oxygen saturation values were measured by NIRS during the first 12 h after birth. Echocardiography alongside Doppler assessment of renal and anterior cerebral arteries were performed at 6, 24, 48 and 72 h of age. Glomerular and tubular functions were also assessed. We found a left ventricular dysfunction together with a higher cerebral oxygen saturation and perfusion values in the IUGR group. IUGR term infants showed a higher renal oxygen saturation and a reduced oxygen extraction together with a subclinical renal damage, as indicated by higher values of urinary neutrophil gelatinase-associated lipocalin and microalbumin. These data suggest that some of the haemodynamic changes present in growth-restricted foetuses may persist postnatally. The increased cerebral oxygenation may suggest an impaired transition to normal autoregulation as a consequence of intra-uterine chronic hypoxia. The higher renal oxygenation may reflect a reduced renal oxygen consumption due to a subclinical kidney damage.

Seizures in children with neurofibromatosis type 1: is neurofibromatosis type 1 enough?

BACKGROUND: Neurofibromatosis type 1 (NF1) is related to a generally increased prevalence of seizures. The mechanism underlying the increased predisposition to seizures has not been fully elucidated. The aim of the study was to evaluate the role of NF1 in seizures pathogenesis in a cohort of children with NF1 and seizures. METHODS: The medical records of 437 children (0-18 years old) with NF1 were reviewed. All children with at least one afebrile seizure were included. Demographic, clinical, neurological, NF1 mutation status, and EEG data were collected along with brain magnetic resonance imaging. Depending on etiology, structural seizures have been identified and were further classified as NF1 related or not. RESULTS: Nineteen patients (4.3%; 13 males) were included. NF1 was inherited in 7 (37.5%), with 3 maternal forms. Ten children with structural seizures were identified. Seven forms were identified someway related to NF1, two of which were associated to 17q11.2 microdeletion and hypoxic-ischemic encephalopathy. Any brain lesion that could explain seizures was found in nine patients, two third of these patients had a familiar history of epilepsy. CONCLUSIONS: Our results suggest seizures are more frequent in NF1 children (4.3%) than in general pediatric population (0.3-0.5%) and that are someway related to NF1 in half of patients. Facing seizures in NF1, the clinician should first exclude brain tumors but also other, and rarer NF1-related scenarios, such as hydrocephalous and vasculopathies. Children with non-structural seizures frequently had a family history of epilepsy, raising questions about the pathogenic role of NF1. They should be approached as for the general population.

Electrocardiographic and echocardiographic changes during therapeutic hypothermia in encephalopathic infants with long-term adverse outcome.

AIM: To assess the electrocardiography and echocardiography changes during therapeutic hypothermia and rewarming period in encephalopathic infants with long-term adverse neurological outcome. METHODS: Prospective multicentre longitudinal study. We included 64 consecutive infants with moderate or severe hypoxic ischaemic encephalopathy undergoing therapeutic hypothermia who had 18-24 month-outcome data. We analysed electrocardiography and heart rate changes before, during and after therapeutic hypothermia. Superior vena cava flow, left ventricular cardiac output and stroke volume were studied using echocardiography during and immediately after therapeutic hypothermia. An abnormal outcome was defined as death or moderate/severe disability at 18-24 months. RESULTS: Neonates with higher superior vena cava flow pre-rewarming had significantly higher odds of documented long-term adverse outcome when compared to newborns with good outcome (OR 1.57; 95%CI, 1.1-1.78; p = 0.01 after adjustment). QTc and RR intervals were significantly longer at 12, 24, 36 and 48 h in infants with good outcome compared with those with adverse outcome (p < 0.001). During therapeutic hypothermia, infants with poor outcome had a higher heart rate at 12, 24, 36, 48, 60 h after birth compared with those with good outcome (p < 0.001). From 36 h on, heart rate gradually increased and RR and QTc intervals progressively shortened with values back to normal after rewarming. CONCLUSIONS: Infants with hypoxic ischaemic encephalopathy who have adverse neurological outcome show a preferential cerebral blood flow redistribution during therapeutic hypothermia. Infants with poor outcome have higher heart rate and shorter RR and QTc intervals during therapeutic hypothermia.