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 .

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.

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.

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.

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.

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.

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.

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.

Climate change and food safety: an emerging issue with special focus on Europe.

According to general consensus, the global climate is changing, which may also affect agricultural and livestock production. The potential impact of climate change on food security is a widely debated and investigated issue. Nonetheless, the specific impact on safety of food and feed for consumers has remained a less studied topic. This review therefore identifies the various food safety issues that are likely to be affected by changes in climate, particularly in Europe. Amongst the issues identified are mycotoxins formed on plant products in the field or during storage; residues of pesticides in plant products affected by changes in pest pressure; trace elements and/or heavy metals in plant products depending on changes in their abundance and availability in soils; polycyclic aromatic hydrocarbons in foods following changes in long-range atmospheric transport and deposition into the environment; marine biotoxins in seafood following production of phycotoxins by harmful algal blooms; and the presence of pathogenic bacteria in foods following more frequent extreme weather conditions, such as flooding and heat waves. Research topics that are amenable to further research are highlighted.

SPECT/CT with a hybrid imaging system in the study of lower gastrointestinal bleeding with technetium-99m red blood cells.

AIM: Lower gastrointestinal (GI) hemorrhage is a complex clinical problem that requires disciplined evaluation for successful management. This study was conducted to evaluate the applicability of single photon emission computed tomography/computed tomography (SPECT/CT) in patients with acute lower gastrointestinal bleeding undergoing scintigraphy with 99mTc-labelled red blood cells (RBC), and to assess the additional clinical value of fused images when compared to the standard radionuclide scan. METHODS: Twenty-seven patients presenting with acute lower GI tract hemorrhage were studied with conventional dynamic and planar 99mTc-RBC imaging. In 19 patients with positive findings on scans taken within 6 hours, a SPECT/CT study was immediately performed using a hybrid system composed of a dual-head, variable angle gamma camera and an X-ray tube. The number of patients in whom SPECT/CT changed the scintigraphic interpretation with regard to the presence or site of GI blood loss as confirmed by other diagnostic or therapeutical procedures was recorded. RESULTS: Image fusion was easy and successful in all patients showing perfect correspondence between SPECT and CT data and allowing precise anatomical localization of the sites of 99mTc-RBC extravasation. SPECT/CT had significant impact on the scintigraphic results in 7/19 patients (36.8%): in 6 patients it precisely localized the bleeding foci whose location could not be identified in standard scans and in one it excluded the presence of an active GI hemorrhage. CONCLUSIONS: SPECT/CT with a hybrid system is feasible and useful for facilitating imaging interpretation and improving the accuracy of 99mTc-RBC scintigraphy in patients with acute lower GI bleeding.

Review of predictive models for Fusarium head blight and related mycotoxin contamination in wheat.

Mould growth and mycotoxin production are related to plant stress caused by environmental factors such as: extreme weather; insect damage; inadequate storage conditions and incorrect fertilization; these predispose plants to mycotoxin contamination in the field. Fusarium species infect wheat during the flowering period. In addition to losses of yield, these fungi can also synthesize toxic components (mycotoxins) in suitable environmental conditions, thus threatening animal and human health. Given the severe consequences and the fact that mycotoxins affect production throughout the world, the ability to predict Fusarium head blight (FHB) and deoxynivalenol (DON) and other mycotoxin contamination is important to reduce the year-to-year risk for producers. Owing to these dangerous consequences in Argentina, Belgium, Canada, Italy, the United States and in Europe, computer models, based on weather variables (temperature, rainfall and moisture level), have been developed to predict the occurrence of FHB and DON contamination in wheat.

Identification of potentially emerging food safety issues by analysis of reports published by the European Community's Rapid Alert System for Food and Feed (RASFF) during a four-year period.

The SAFE FOODS project undertakes to design a new approach towards the early identification of emerging food safety hazards. This study explored the utility of notifications filed through RASFF, the European Commission's Rapid Alert System for Food and Feed, to identify emerging trends in food safety issues. RASFF information and alert notifications published in the four-year period of July 2003-June 2007 were assigned to categories of products and hazards. For chronological trend analysis, a basic time unit of three months was chosen. Data within each hazard category were analyzed for chronological trends, relationships between product and hazard categories, regions of origin, and countries filing the notifications. Conspicuous trends that were observed included a rise in the incidence of food contact substances, particularly 2-isopropyl-thioxanthone, as well as of chemical substances migrating from utensils and fraud-related issues. Temporary increases were noted in the incidences of the unauthorized dye Para Red, genetically modified organisms, the pesticide isophenfos-methyl, and herring worm, Anisakis simplex. National and European authorities themselves have signaled these conspicuous trends and taken measures. It is recommended to add complementary data to RASFF data, including safety assessments, risk management measures, background data on hazards and surveillance patterns, for a holistic approach towards early identification of emerging hazards.

On the occurrence of aflatoxin M1 in milk and dairy products.

Aflatoxins are toxic fungal metabolites found in foods and feeds. When ruminants eat AFB(1)-feedstuffs, they metabolise the toxin and excrete AFM(1) in milk. To control AFM(1) in foods it is necessary to reduce AFB(1) contamination of feeds for dairy cattle by preventing fungal growth and AFB(1) formation in agricultural commodities intended for animal use. Corn and corn-based products are one of the most contaminated feedstuffs; therefore risk factor analysis of AFB(1) contamination in corn is necessary to evaluate risk of AFM(1) contamination in milk and milk products. During the corn silage production, the aflatoxins production is mostly influenced by: harvest time; fertilization; irrigation; pest control; silage moisture; and storage practices. Due to the lower moisture at harvest and to the conservation methods, the corn grain is mostly exposed to the contamination by Aspergillus species. Therefore, it is necessary to reduce the probability of this contaminant through choice of: hybrids; seeding time and density; suitable ploughing and fertirrigation; and chemical or biological control. Grains harvested with the lowest possible moisture and conservation moisture close to or less than 14% are necessary to reduce contamination risks, as is maintaining mass to homogeneous moisture. Kernel mechanical damage, grain cleaning practices and conservation temperature are also factors which need to be carefully controlled.

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.

The Value of Semi-Quantitative Analysis of 123I-FP-CIT SPECT in Evaluating Patients with Parkinson's Disease.

(123)I-FP-CIT SPECT binding to striatal dopamine transporter (DAT) is markedly reduced in patients with Parkinson's disease (PD) and it may also help in identifyng pre-symptomatic nigrostriatal dysfunction in subjects at risk. This study used semi-quantitative analysis of 123I-FP-CIT SPECT to evaluate the possibility of a more extensive and earlier diagnosis of dopaminergic damage. We used qualitative visual assessment and semiquantitative measures of striatal DAT binding using (123)I-FP-CIT SPECT in 154 patients with suspected PD. A control group comprised 18 people age-matched to the PD group whose follow-up disclosed essential tremor. Abnormal striatal 123I-FP-CIT uptake was evident in 134 out of 154 patients (87%). Qualitative visual assessment showed striatal dopaminergic (123)I-FP-CIT uptake was significantly reduced in 60.4% (controlateral putamen to the symptoms), in 31.3% (caudate nucleus) and in 8.3% (ipsolateral basal ganglia to the symptoms). Semi-quantitative analysis showed the following results: 32.8%, 50.7% and 16.5% respectively. We compared these two assessments and their correlation with PD clinical progression. At 24 month follow-up, patients with greater dopaminergic damage at semiquantitative analysis showed a more severe motor disability. Our findings indicate that (123)I-FP-CIT SPECT with semiquantitative analysis can offer a more accurate characterization of the dopaminergic damage in patients with suspected Parkinson's disease.