LUNCH-Lung Ultrasound for early detection of silent and apparent aspiratioN in infants and young CHildren with cerebral palsy and other developmental disabilities: study protocol of a randomized controlled trial.

BACKGROUND: Children with neurological impairment may have dysphagia and/or gastro-esophageal reflux disease (GERD), which predispose to complications affecting the airways, increasing risk for aspiration-induced acute and chronic lung disease, or secondarily malnutrition, further neurodevelopmental disturbances, stressful interactions with their caregivers and chronic pain. Only multidisciplinary clinical feeding evaluation and empirical trials are applied to provide support to the management of feeding difficulties related to dysphagia or GERD, but no standardized feeding or behavioral measure exists at any age to assess aspiration risk and support the indication to perform a videofluoroscopic swallowing study (VFSS) or a fibre-optic endoscopic examination of swallowing (FEES), in particular in newborns and infants with neurological impairments. Lung ultrasound (LUS) has been proposed as a non-invasive, radiation-free tool for the diagnosis of pulmonary conditions in infants, with high sensitivity and specificity. METHODS: A RCT will be conducted in infants aged between 0 and 6 years having, or being at risk for, cerebral palsy, or other neurodevelopmental disease that determines abnormal muscular tone or motor developmental delay assessed by a quantitative scale for infants or if there is the suspicion of GERD or dysphagia based on clinical symptoms. Infants will be allocated in one of 2 groups: 1) LUS-monitored management (LUS-m); 2) Standard care management (SC-m) and after baseline assessment (T0), both groups will undergo an experimental 6-months follow-up. In the first 3 months, infants will be evaluated a minimum of 1 time per month, in-hospital, for a total of 3 LUS-monitored meal evaluations. Primary and secondary endpoint measures will be collected at 3 and 6 months. DISCUSSION: This paper describes the study protocol consisting of a RCT with two main objectives: (1) to evaluate the benefits of the use of LUS for monitoring silent and apparent aspiration in the management of dysphagia and its impact on pulmonary illness and growth and (2) to investigate the impact of the LUS management on blood sample and bone metabolism, pain and interaction with caregivers. TRIAL REGISTRATION: Trial registration date 02/05/2020; ClinicalTrials.gov Identifier: NCT04253951 .

Assessing upper limb function in multiple sclerosis using an engineered glove.

BACKGROUND AND PURPOSE: The importance of upper limb function in multiple sclerosis (MS) is increasingly recognized, especially for the evaluation of patients with progressive MS with reduced mobility. Two sensor-engineered gloves, able to measure quantitatively the timing of finger opposition movements, were previously used to assess upper limb disability in MS. The aims of the present study were: (1) to confirm the association between glove-derived variables and standard measures of MS disability in a larger cohort; (2) to assess the correlation with quantitative magnetic resonance imaging (MRI) and quality of life (QoL) measures; and (3) to determine if the glove-derived variables offer advantages over the standard measure for assessing upper limb function in MS, namely, the Nine-Hole Peg Test (9HPT). METHODS: Sixty-five patients with MS, stable on disease-modifying treatment, were evaluated at baseline using the glove, and through clinical examination (Expanded Disability Status Scale, Symbol Digit Modalities Test, Timed 25-Foot Walk Test and 9HPT), MRI evaluation and QoL questionnaires. Correlations between the glove-derived variables and clinical, MRI and QoL variables were assessed using Spearman's rank correlation coefficient analysis. RESULTS: Glove-derived variables significantly differed between patients with relapsing-remitting and those with progressive MS, with similar or slightly higher correlations of the 9HPT with clinical variables. We found greater correlations of the QoL physical component with glove-derived variables than with the 9HPT, and a significant correlation of its mental component with the glove-derived variables but not with the 9HPT. CONCLUSION: The study results, confirming previous findings and showing advantages over the 9HPT, encourage the investigation of sensitivity to change in glove-derived variables in a longitudinal setting.

Radioembolisation with (90)Y-labelled resin microspheres in the treatment of liver metastasis from breast cancer.

OBJECTIVES: Metastatic breast cancer is a heterogeneous disease, commonly affecting the liver. We report our experience with (90)Y radioembolisation (RE) and its effects on the survival of patients with treatment-refractory breast cancer liver metastases. METHODS: A total of 77 female patients affected by breast cancer were accepted into our department for RE. Inclusion criteria were inoperable and chemotherapy-refractory hepatic metastases, acceptable performance status, sufficient residual liver, no significant hepato-pulmonary shunts. Patients were divided in two groups: group 1 (29 patients) included those with Eastern Cooperative Oncology Group (ECOG) score 0, liver involvement (0-25 %) and no extrahepatic disease (EHD); group 2 (23 patient) included patients with ECOG score 1-2, liver involvement (26-50 %) and evidence of EHD. RESULTS: A total of 25 patients were considered ineligible. The median age of the remaining 52 patients was 57.5 years. The median overall survival was 11.5 months and better in those whose performance status and liver function were preserved (14.3 versus 8.2 months). According to Response Evaluation Criteria in Solid Tumor (RECIST), partial response (PR) was achieved in 29 patients (56 %), stable disease (SD) was achieved in a further 18 patients (35 %) and 5 patients showed progressive disease (PD) (10 %). DISCUSSION: (90)Y RE is effective in the treatment of liver metastases from breast cancer. We demonstrated a relevant survival and encouragingly high response rate in patients with treatment-refractory disease.

Pulmonary embolism in patients with COVID-19 pneumonia: When we have to search for it?

BACKGROUND: COVID-19 is still a global challenge in regard for management and therapy. Pulmonary embolism (PE) seems to have a higher prevalence in COVID-19 instead of non-COVID patients. Clinical and laboratory parameters related with PE are still unknown. METHODS: We conducted a retrospective unicentre study in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 in patients admitted for COVID-19 tested with a RT-PCR nasal swab. Data about patients studied with computed tomography pulmonary angiogram (CTPA) because of PE suspicion were collected, as their clinical and laboratory parameters too. RESULTS: 2621 patients were admitted for COVID-19 in Alto Vicentino Hospital between March 1st, 2020, and January 31st, 2021 and in 267 of them a CTPA was performed finding 50 PE (18.7%). Only non-Caucasian race (OR = 5.44; 95% CI 1.22-24.35; p = 0.027) and previous VTE (OR = 5.3; 95% CI 1.09-26.17; p = 0.039) were found to be independently associated with PE. CONCLUSION: PE is a frequent complication of COVID-19 and clinician need high degree of suspicion because clinical and laboratoristic parameters cannot drive diagnosis.

Cortical metabolic changes and clinical outcome in normal pressure hydrocephalus after ventriculoperitoneal shunt: Our preliminary results. / Cambios metabólicos corticales y resultado clínico en la hidrocefalia normotensiva después de la derivación ventrículo-peritoneal: nuestros resultados preliminares.

INTRODUCTION: Our objective was to evaluate the cortical metabolic changes and clinical outcome in patients affected by idiopathic normal pressure hydrocephalus (iNPH) after a placement of ventriculoperitoneal (VP) shunt. MATERIALS AND METHODS: 10 patients affected by suspected iNPH underwent a CSF hydrodynamics evaluation based on a lumbar infusion test (LIT). The main selection criterion for surgery was based on intracranial elasticity (IE)>0.30. All subjects with an IE>0.30 underwent a PET scan with 18 fluorodeoxiglucose (18F-FDG) at baseline (PET1) and 1 month after surgery (PET2). Furthermore, the same patients were submitted to clinical evaluation before and 1 month after surgery through neuropsychological tests and gait analysis. RESULTS: An overall number of 20 18F-FDG PET scans were performed in all the enrolled patients. As compared to PET1, PET2 showed an increase in glucose consumption in the left frontal and left parietal lobe in PET2 as compared to PET1 (P<.001). All the enrolled patients presented a significant increase in neuropsychological scores (i.e Frontal Assessment Battery and Montreal Cognitive Assessment) and have clinically improved at gait analysis. A significant correlation was found between the increase of cortical glucose consumption in the left parietal area and the cognitive improvement as detectable by neuropsychological assessment. CONCLUSIONS: Improvement in 18F FDG PET glucose metabolism could be considered a useful imaging marker for the assessment of iNPH response to VP shunting.

PET-guided Switch from Immunotherapy to Targeted Therapy in a Metastatic Melanoma Patient: a personalized approach.

An early identification of non-responders in oncology is of crucial importance to rapidly switch treatment regimens. Here we report a positron emission tomography, (PET)-guided switch from immunotherapy to targeted therapy in a patient affected by metastatic melanoma. We describe the case of a 78-years-old male patient diagnosed with nodular melanoma, submitted to baseline PET/CT with 18fluorodeoxyglucose (18F-FDG) that showed cutaneous and skeletal metastases (stage IV). The patients started immunotherapy with pembrolizumab. A PET/CT performed 3 months after the start of immunotherapy demonstrated progressive metabolic disease both at skeletal and cutaneous level, confirmed also by the biopsy. As patients resulted positive for BRAF V600k mutation, treatment regimen was rapidly switched to combined anti-BRAF/MEK targeted therapy. The PET/CT performed 3 months later, showed almost complete metabolic response. Ten months after the beginning of targeted therapy, the patient continues to present a durable metabolic response. PET/CT with 18F-FDG may help in monitoring the response to treatment in metastatic melanoma thus defining personalized therapeutic pathways.

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.

Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia.

A case of a child with recurrent episodes of severe hypoglycemia since the age of 6 months is reported. Biochemical evaluation extended to the first-degree relatives is consistent with a familial form of hypoglycemia due to a leucine-sensitive hyperinsulinism. In addition, this patient has a persistent elevation of serum ammonia levels of uncertain etiology that is more pronounced after meals. Urea cycle defects, organic acidurias, and beta-oxidation defects have been ruled out, as well as a possible excessive deamination of glucogenetic amino acids. This unexpected hyperammonemia, which was also detected in the mother, might be related to leucine hypersensitivity.

Reproducibility of electrophysiological parameters of sinus node following autonomic blockade.

We investigated the reproducibility of sinus node cycle length (SCL), corrected sinus node recovery time (CSRT) and sino-atrial conduction time (SACT) during the control state and following autonomic blockade in 25 patients (mean age: 56.9 +/- 13.8 years). Autonomic blockade was induced by i.v. administration of propranolol (0.2 mg/kg) and atropine (0.04 mg/kg). The electrophysiological study was repeated after 24 hr and the results were compared. The patients were divided into two groups: Group 1 (15) with normal and Group 2 (10) with abnormal intrinsic sinus node function. Following autonomic blockade in Group 1 the daily variations in SCL, CSRT and SACT were very slight whereas in Group 2 there was far greater variability in these parameters. However, in the latter group there were no patients who changed their status from prolonged to normal intrinsic CSRT on the second study, whereas SACT changed its status in 2 patients. In Group 1 the daily variations in sinus node parameters were much slighter following autonomic blockade than during the control state. In Group 2 the variations were very similar during control and following autonomic blockade. These data suggest that: (1) following autonomic blockade the reproducibility of sinus node parameters is very good in Group 1, whereas in Group 2 several patients show marked daily variations in sinus node parameters; (2) following autonomic blockade the sinus node electrophysiological parameters are meaningful in diagnosing an involvement of intrinsic sinus node function; and (3) in patients with abnormal sinus node parameters during control state, but with normal intrinsic sinus node function, the daily variations are mainly due to change in autonomic tone, whereas when the intrinsic sinus node function is abnormal, the day to day variations during control state appear due predominantly to intrinsic sinus node abnormalities.

Plasma bilirubin level and oxidative stress in preterm infants.

OBJECTIVE: To assess the hypothesis that changes in plasma total bilirubin levels (Btot) can influence the antioxidant system and oxidative stress in preterm infants. METHODS: Twenty two healthy preterm infants who presented with visible non-haemolytic hyperbilirubinaemia were studied at the mean (SD) age of 3.7 (1.5) days. Btot, plasma total hydroperoxide concentration (TH), plasma protein SH group concentration, and total antioxidant capacity of the plasma (TAC) were measured at study entry and after 24 hours. RESULTS: Btot did not correlate with TH, TAC, or protein SH group concentration, but a significant correlation was found between TH and TAC, TH and protein SH groups, and TAC and protein SH groups, both at study entry and after 24 hours. CONCLUSION: The decrease in plasma bilirubin was contemporary with an increase in plasma antioxidant capacity and decrease in oxidative stress in preterm infants. This may be the result of the pro-oxidant effect of haem oxygenase, mediated by iron release, which may outcompete the antioxidant properties of bilirubin.

Pharmacokinetics of oxatomide in preterm infants.

The pharmacokinetics and tolerability of oxatomide oral suspension were investigated in preterm infants to evaluate the feasibility of planning a further study to assess its antiinflammatory effects and its effectiveness in preventing chronic lung disease (CLD). Following the administration of oxatomide 1 mg/kg, the peak plasma concentration (Cmax), the elimination half-life (t1/2), the volume of distribution (Vd), and the area under the curve (AUC) 0-36 h were measured and the following results were obtained: 42.2 +/- 15 ng/ml at 2 h after oxatomide administration, 41.4 +/- 2.0 h, 37.4 +/- 4.2 l/kg, and 468 +/- 52 ng/ml/h, respectively. Our study, therefore, demonstrated that a dose of 1 mg/kg/day oxatomide was effective in reaching therapeutic plasma levels in preterm infants without inducing adverse effects.

Dental and craniofacial findings in a child affected by glycogen storage disease type III.

This paper reports on previously undescribed dentofacial features a child suffering from Glycogen-Storage Disease type III with hepatomegaly and hypertransaminasemia with muscular involvement. Deficient craniofacial development, reduced width of the upper jaw resulting in posterior cross-bite, and taurodontism of the primary dentition were found. Pathogenetic basis for craniofacial abnormalities is discussed. Cooperation between pediatricians and pediatric dentists is strongly recommended for an early diagnosis and treatment of the dentofacial defects of the syndrome.

[Pilot studies on the effect of desmopressin on the personality of enuretic children]. / Studio pilota sugli effetti della desmopressina sulla personalità di bambini enuretici.

The aim of this paper was to establish if there is a correlation between desmopressin administration and modification of psychological experience in enuretic children. 22 enuretic children (18 treated with desmopressin, 4 not treated) were enrolled in the study. They underwent a complete psychological examination, differentiated on the basis of chronological age, before the beginning and at the end of the treatment (duration 4 months). The psychologist was not informed if they were treated or not. In the 17 of 18 treated children with basal psychological problems, 14 became normal, 2 demonstrated a significative amelioration and 1 remained pathologic at the end of the treatment. No modification was observed in not treated patients, all presenting psychological problems. 6 emblematic cases with psychological findings and paintings are presented. The results seem interesting, despite the low number of children enrolled.

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.

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.

The value of 64-detector row computed tomography for the exclusion of pulmonary embolism.

Recently, a diagnostic strategy using a clinical decision rule, D-dimer testing and spiral computed tomography (CT) was found to be effective in the evaluation of patients with clinically suspected pulmonary embolism (PE). However, the rate of venous thromboembolic complications in the three-month follow-up of patients with negative CT was still substantial and included fatal events. It was the objective to evaluate the safety of withholding anticoagulants after a normal 64-detector row CT (64-DCT) scan from a cohort of patients with suspected PE. A total of 545 consecutive patients with clinically suspected first episode of PE and either likely pre-test probability of PE (using the simplified Wells score) or unlikely pre-test probability in combination with a positive D-dimer underwent a 64-DCT. 64-DCT scanning was inconclusive in nine patients (1.6%), confirmed the presence of PE in 169 (31%), and ruled out the diagnosis in the remaining 367. During the three-month follow-up of the 367 patients one developed symptomatic distal deep-vein thrombosis (0.27%; 95%CI, 0.0 to 1.51%) and none developed PE (0 %; 95%CI, 0 to 1.0%). We conclude that 64-DCT scanning has the potential to safely exclude the presence of PE virtually in all patients presenting with clinical suspicion of this clinical disorder.