The efficacy of trabecular titanium cages to Induce reparative bone activity after lumbar arthrodesis studied through the 18f-Naf PET/CT scan: observational clinical in-vivo study

Background: Titanium trabecular cages (TTCs) are emerging implants designed to achieve immediate and long-term spinal fixation with early osseointegration. However, a clear radiological and clinical demonstration of their efficacy has not yet been obtained. The purpose of this study was to evaluate the reactive bone activity of adjacent plates after insertion of custom-made titanium trabecular cages for the lumbar interbody with positron emission tomography (PET)/computed tomography (CT) 18F sodium fluoride (18F-NaF). Methods: This was an observational clinical study that included patients who underwent surgery for degenerative disease with lumbar interbody fusion performed with custom-made TTCs. Data related to the metabolic-reparative reaction following the surgery and its relationship with clinical follow-up from PET/CT performed at different weeks were evaluated. PET/CTs provided reliable data, such as areas showing abnormally high increases in uptake using a volumetric region of interest (VOI) comprising the upper (UP) and lower (DOWN) limits of the cage. Results: A total of 15 patients was selected for PET examination. Timing of PET/CTs ranged from one week to a maximum of 100 weeks after surgery. The analysis showed a negative correlation between the variables SUVmaxDOWN/time (r = −0.48, p = 0.04), ratio-DOWN/time (r = −0.53, p = 0.02), and ratio-MEAN/time (r = −0.5, p = 0.03). Shapiro−Wilk normality tests showed significant results for the variables ratio-DOWN (p = 0.002), ratio-UP (0.013), and ratio-MEAN (0.002). Conclusions: 18F-NaF PET/CT has proven to be a reliable tool for investigating the metabolic-reparative reaction following implantation of TTCs, demonstrating radiologically how this type of cage can induce reparative osteoblastic activity at the level of the vertebral endplate surface. This study further confirms how electron-beam melting (EBM)-molded titanium trabecular cages represent a promising material for reducing hardware complication rates and promoting fusion

Identification of histone deacetylase inhibitors with (arylidene)aminoxy scaffold active in uveal melanoma cell lines

Uveal melanoma (UM) represents an aggressive type of cancer and currently, there is no effective treatment for this metastatic disease. In the last years, histone deacetylase inhibitors (HDACIs) have been studied as a possible therapeutic treatment for UM, alone or in association with other chemotherapeutic agents. Here we synthesised a series of new HDACIs based on the SAHA scaffold bearing an (arylidene)aminoxy moiety. Their HDAC inhibitory activity was evaluated on isolated human HDAC1, 3, 6, and 8 by fluorometric assay and their binding mode in the catalytic site of HDACs was studied by molecular docking. The most promising hit was the quinoline derivative VS13, a nanomolar inhibitor of HDAC6, which exhibited a good antiproliferative effect on UM cell lines at micromolar concentration and a capability to modify the mRNA levels of HDAC target genes similar to that of SAHA

Quality of Life in Chronic Ketogenic Diet Treatment : the GLUT1DS Population Perspective

BACKGROUND: Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a rare, genetically determined neurological disorder, for which Ketogenic Diet (KD) represents the gold standard life-long treatment. The aim of this study is to investigate health related quality of life in a well characterized cohort of patients affected by GLUT1DS treated with KD, evaluating factors that can influence patients' and parents' quality of life perception. METHODS: This is a double center exploratory research study. A postal survey with auto-administrable questionnaires was conducted among 17 subjects (aged 3-22 years) with diagnosis of GLUT1DS, receiving a stable KD treatment for more than 1 year. The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales was adopted. Clinical variables analyzed in relation to quality of life were frequency of epileptic seizures and movement disorder since KD introduction, presence of intellectual disability (ID), and KD ratio. RESULTS: Quality of life global scores were impaired both in parents' and children's perspectives, with a significant concordance. Taking into consideration subscales, the average was 64.17 (range 10-100) for physical functioning, 74.23 (range 30-100) for emotional functioning, 62.64 (range 10-100) for social functioning, and 56 (range 15-92) for school functioning. CONCLUSIONS: In patients with GLUT1DS the quality of life perception is comparable to that of other patients with chronic disease. In our sample, the presence of movement disorder seems to be a crucial element in quality of life perception

A multicenter evaluation of a deep learning software (LungQuant) for lung parenchyma characterization in COVID-19 pneumonia

BackgroundThe role of computed tomography (CT) in the diagnosis and characterization of coronavirus disease 2019 (COVID-19) pneumonia has been widely recognized. We evaluated the performance of a software for quantitative analysis of chest CT, the LungQuant system, by comparing its results with independent visual evaluations by a group of 14 clinical experts. The aim of this work is to evaluate the ability of the automated tool to extract quantitative information from lung CT, relevant for the design of a diagnosis support model.MethodsLungQuant segments both the lungs and lesions associated with COVID-19 pneumonia (ground-glass opacities and consolidations) and computes derived quantities corresponding to qualitative characteristics used to clinically assess COVID-19 lesions. The comparison was carried out on 120 publicly available CT scans of patients affected by COVID-19 pneumonia. Scans were scored for four qualitative metrics: percentage of lung involvement, type of lesion, and two disease distribution scores. We evaluated the agreement between the LungQuant output and the visual assessments through receiver operating characteristics area under the curve (AUC) analysis and by fitting a nonlinear regression model.ResultsDespite the rather large heterogeneity in the qualitative labels assigned by the clinical experts for each metric, we found good agreement on the metrics compared to the LungQuant output. The AUC values obtained for the four qualitative metrics were 0.98, 0.85, 0.90, and 0.81.ConclusionsVisual clinical evaluation could be complemented and supported by computer-aided quantification, whose values match the average evaluation of several independent clinical experts

Validity of the Severity of Dependence Scale for detecting dependence behaviours in chronic migraine with medication overuse

Aims: In this study, we tested the validity of the Severity of Dependence Scale in detecting dependence behaviours in patients with chronic migraine and medication overuse (CM + MO) using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Leeds Dependence Questionnaire as gold standard measures. Methods: Four hundred and fifty-four patients with CM + MO filled in the Severity of Dependence Scale and the Leeds Dependence Questionnaire and underwent a psychological evaluation for the diagnosis of substance dependence according to the DSM-IV criteria. Results: Sixty-nine percent of subjects (n = 313) presented substance dependence according to the DSM-IV criteria. These patients scored significantly higher than those without substance dependence in Severity of Dependence Scale total score (Z = −3.29, p = 0.001), and in items 1 (Z = −2.44, p = 0.015), 2 (Z = −2.50, p = 0.012), 4 (Z = −2.05, p = 0.04), and 5 (Z = −3.39, p = 0.001). Severity of Dependence Scale total score (β = 0.13, SE = 0.04, z = 3.49, p < 0.001) was a significant predictor for substance dependence. Receiver Operating Characteristic (ROC) curves showed that Severity of Dependence Scale discriminated patients with or without substance dependence. Conclusion: Severity of Dependence Scale could represent an interesting screening tool for dependency-like behaviors in CM + MO patients

A global perspective on parental stress in the neonatal intensive care unit: a meta-analytic study

Objectives: The Parental Stressor Scale: Neonatal Intensive Care Unit (PSS:NICU) is a well-validated tool to assess different sources of stress in parents during the NICU hospitalization of their infant. The present meta-analytic study assessed the relative impact of different NICU-related sources of parental stress in a pool of studies conducted in a wide set of different countries. Also, differences in stress levels by parent gender and country, as well as the impact of infants’ neonatal characteristics and clinical conditions were explored. Methods: Records were searched on PubMed, Scopus, and Web of Science (January 1993–December 2019). A purposive open search string was adopted: [“PSS:NICU”] OR [“PSS-NICU”] OR [“Parental Stressor Scale”]. A multiple random-effect meta-analysis was conducted on data from 53 studies extracted by independent coders. Results: Parental role alteration emerged as the greatest source of stress for both mothers and fathers. Mothers reported higher stress levels compared to fathers. A significant difference emerged only for the subscale related to sights and sounds physical stimuli. No significant effects of infants’ neonatal characteristics (gestational age, birth weight) and clinical conditions (comorbidities) emerged. A marginal positive effect of NICU length of stay emerged on the global level of parents’ stress. Conclusions: The current meta-analysis underlines that parental stress related to NICU admission is a worldwide healthcare issue. Immediate and tailored support to parents after the birth of their at-risk infant should be prioritized to reduce parental stress and to promote mothers and fathers’ emotional well-being and new-born neurodevelopmental outcomes

Visual function in children with Joubert syndrome

Aim: To describe visual function in children with Joubert syndrome and to investigate its possible association with diagnostic and developmental aspects. Method: This retrospective cross-sectional work included 59 patients (33 male; mean age 9 years 2 months, standard deviation 6 years 3 months, range 4 months to 23 years) diagnosed with Joubert syndrome from January 2002 to December 2020. Data about clinical (neurological, neuro-ophthalmological, developmental/cognitive) and diagnostic (e.g. genetic testing, neuroimaging, systemic involvement) evaluations were collected in a data set during a review of medical records. Clinical and diagnostic variables were described in terms of raw counts and percentages. A χ2 test was conducted to investigate their association with neuropsychological skills. Results: Ocular motor apraxia was highly represented in our cohort (75%), with a high prevalence of refractive defects and retinal abnormalities. Developmental delay/intellectual disability was frequent (in 69.5% of the sample), associated with retinal dystrophy (p = 0.047) and reduced visual acuity both for near (p = 0.014) and for far distances (p = 0.017). Interpretation: On the basis of the relevance of oculomotor and perceptual alterations and their impact on overall and cognitive impairment, we encourage early and multidisciplinary assessment and follow-up of visual function in children with Joubert syndrome. This would help in planning a personalized rehabilitation to sustain functional vision. Further studies will be important to explore the link between biological aspects and global functioning in children with Joubert syndrome. What this paper adds: Perceptual deficits and oculomotor impairments frequently coexist in Joubert syndrome. Retinal dysfunction may be present despite the absence of funduscopic abnormalities. Both perceptual and oculomotor impairments negatively affect cognitive development in Joubert syndrome

Arterial spin labelling qualitative assessment in paediatric patients with MRI-negative epilepsy

AIM: To evaluate the usefulness of arterial spin labelling (ASL) qualitative analysis for the localisation of seizure-related perfusion abnormalities in paediatric patients with negative brain magnetic resonance imaging (MRI) epilepsy. MATERIALS AND METHODS: Forty-two patients with a diagnosis of MRI-negative focal or generalised epilepsy, who underwent electroencephalogram (EEG) and MRI with ASL in the interictal phase were included. Perfusion abnormalities were evaluated through a qualitative assessment and then compared to EEG seizure focus. RESULTS: Among the 42 patients, 26 had focal epilepsy and 16 had generalised epilepsy. Thirty-three patients (79%) showed a perfusion abnormality, mainly hypoperfusion (74.5% of all ASL alterations), whereas hyperperfused alterations were more represented in patients who experienced the last seizure either less than 48 hours prior to ASL acquisition or in the time interval from 1 week to 1 month prior to ASL acquisition (p=0.034). Concordance of ASL abnormality and EEG focus was found in 33 patients (78.5%), as complete in 17 (40.5%) and as partial in 16 (38%). A trend of higher concordance was found in focal epilepsies compared to generalised epilepsies (p=0.059). The concordance between ASL and EEG major alterations was higher for hyperperfused anomalies than for hypoperfused ones (p=0.009). Variables such as age, sedation, and time from last seizure were not significant contributors for concordance. CONCLUSIONS: The combined use of qualitative ASL and brain MRI and scalp EEG could be a potential tool in daily clinical practice