Comorbidities in Dravet Syndrome and Lennox–Gastaut Syndrome

AbstractThis study aims to describe the main cognitive and behavioral comorbidities of Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS), their impact on the health-related quality of life (QOL) of patients and their caregivers, and provide a summary of the neuropsychological tools available for the evaluation of these comorbidities. The cognitive and behavioral comorbidities in patients with DS and LGS have a profound effect on the QOL of affected individuals and their caregivers and, as patients grow, tend to surpass the impact of the seizures. DS is a genetic condition associated with loss-of-function mutations in the SCNA1 sodium channel gene; LGS is an etiologically heterogeneous condition that is often secondary to structural brain abnormalities. The first seizures associated with DS typically present in the first year of life, and developmental delay becomes progressively evident thereafter. LGS usually starts between the ages of 3 and 8 years, with cognitive impairment becoming clinically evident in most patients within 5 years from the onset. In both DS and LGS, cognitive impairment is generally moderate to severe and is often accompanied by behavioral problems such as hyperactivity and inattention. In addition to optimal seizure control, regular assessment and active management of cognitive and behavioral comorbidities are required to meet the complex needs of patients with DS or LGS

Upper airway involvement in pediatric COVID-19

The clinical spectrum of SARS-CoV-2 infection is mixed. It ranges from asymptomatic cases, medium-intensity forms with mild to moderate symptoms, to severe ones with bilateral lung involvement and respiratory distress, which can require transfer to ICUs and intubation. In most cases, the clinical picture is characterized by a persistent fever, cough, dyspnoea, expectoration, myalgias, arthralgias, headache, gastrointestinal symptoms, nasal congestion, and pharyngodynia. The spread of COVID-19 in Europe has highlighted an atypical presentation of disease involving upper airways and, above all, dysfunction of olfactory and gustatory senses. There is ample evidence that COVID-19 is significantly less severe in children than in adults. However, due to difficulties in assessing the disorder in children, especially among very young patients, the olfaction and gustatory dysfunctions remain open issues. This article sheds light on the upper airway involvement in pediatric COVID-19 subjects

Targeted next generation sequencing in Italian patients with Usher syndrome: Phenotype-genotype correlations

Abstract We report results of DNA analysis with next generation sequencing (NGS) of 21 consecutive Italian patients from 17 unrelated families with clinical diagnosis of Usher syndrome (4 USH1 and 17 USH2) searching for mutations in 11 genes: MYO7A, CDH23, PCDH15, USH1C, USH1G, USH2A, ADGVR1, DFNB31, CLRN1, PDZD7, HARS. Likely causative mutations were found in all patients: 25 pathogenic variants, 18 previously reported and 7 novel, were identified in three genes (USH2A, MYO7A, ADGRV1). All USH1 presented biallelic MYO7A mutations, one USH2 exhibited ADGRV1 mutations, whereas 16 USH2 displayed USH2A mutations. USH1 patients experienced hearing problems very early in life, followed by visual impairment at 1, 4 and 6 years. Visual symptoms were noticed at age 20 in a patient with homozygous novel MYO7A missense mutation c.849G > A. USH2 patients’ auditory symptoms, instead, arose between 11 months and 14 years, while visual impairment occurred later on. A homozygous c.5933_5940del;5950_5960dup in USH2A was detected in one patient with early deafness. One patient with homozygous deletion from exon 23 to 32 in USH2A suffered early visual symptoms. Therefore, the type of mutation in USH2A and MYO7A genes seems to affect the age at which both auditory and visual impairment occur in patients with USH

Cross-sectional survey on impact of paediatric COVID-19 among Italian paediatricians: report from the SIAIP rhino- sinusitis and conjunctivitis committee

Background: There is ample evidence that COVID-19 is significantly less severe in children than in adults and asthma and allergy, the most common chronic disorders in children, are not included in the top 10 comorbidities related to COVID-19 fatalities. Nevertheless, concerns about asthma and allergy are still high.. In order to evaluate the impact of paediatric COVID-19 among Italian paediatricians, we sent a 20-questions anonymous internet-based survey to 250 Italian paediatricians with particular address to allergic symptoms and those affecting the upper airways. Methods: The questionnaire was conceived and pretested in April 2020, by a working group of experts of the Italian Paediatric Society for Allergy and Immunology (SIAIP), and structured into different sections of 20 categorized and multiple choice questions. The first part included questions about epidemiological data follows by a second part assessing the way to manage a suspected COVID-19 infection and personal experiences about that. The third part concerned questions about patients’ clinical characteristics and clinical manifestations. The survey was emailed once between April and mid-May 2020. Results: A total 99 participants had participated in our survey and provided responses to our electronic questionnaire. The distribution of patients reported per month varies significantly according to the geographical area (P = 0.02). Data confirmed that in the North part of Italy the rate of patients referred is higher than in the rest of Italy. Almost all respondents (98%) reported caring for up to a maximum of 10 infected children and the last 2% more than twenty. Among these patients, according to the 75% of responders, a maximum rate of 20% were affected by allergic rhino-conjunctivitis and in particular in the North of Italy while in the Centre and in the South there was a higher incidence (P = 0.09). Almost the same applies for asthma, 83% of responders declared that up to a maximum of 20% of affected children were asthmatic, from 20 to 40% for the 13,5% of responders and from 40 to 60% for the last 3,5%. As for the allergic conjunctivitis also for asthma, we found a higher incidence in the Centre and in South than in the North (P = 0.03). Conclusions: This study is the first to provide a comprehensive review of COVID-19 knowledge and impact among paediatricians in Italy about allergic asthma and upper airway involvement. From our point of view, it provides important information clearly useful for improving a good practice

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Wall drawing 445 e Wall drawing 494 di Sol Lewitt. Si conserva il progetto o anche la sua esecuzione? Studio della fase progettuale, della tecnica esecutiva e dello stato di conservazione

I Wall Drawing 445 e Wall Drawing 494 di Sol LeWitt vennero dipinti nell'ex granaio della Fattoria di Celle per Giuliano Gori tra il 1985 e il 1986. Le opere, nate dal progetto di uno dei principali esponenti dell'Arte Concettuale, possono essere considerate la trasposizione di un'idea che, prendendo forma dapprima in un diagramma cartaceo e in una serie di indicazioni tecniche, viene successivamente trasferita alla dimensione architettonica della parete. Un progetto che nasce nella mente di LeWitt e che altri possono materialmente eseguire. È stata proprio la natura di queste opere che ha fornito l'occasione per alcune riflessioni, maturate all'interno del cantiere didattico del Master in Conservazione e restauro delle opere d’arte contemporanea presso l’Opificio delle Pietre Dure, nel tentativo di dare risposta a quesiti di natura sia tecnica che teorica

Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients: pharmacokinetic parameters and clinical implications

Abstract Background Hepatocyte Growth Factor (HGF) enhances cytotoxicity of paclitaxel (PTX) and cisplatin (CDDP) in human ovarian cancer cells. Because of potential pitfalls of HGF exogenous administration, we investigated whether HGF serum concentration might be alternatively raised in vivo by administering low molecular weight heparin (LMWH). Methods The main HGF pharmacokinetic parameters were evaluated following acute and chronic LMWH treatment. First, women, operated on for gynaecological tumors, were treated with a single dose of calcium nadroparin and studied for 12 hours. Next, women operated on for benign or malignant gynaecological tumors were treated daily with calcic nadroparin for one month. Subsequently, the biological activity of the measured HGF serum levels was tested in assays of ovarian cancer cell sensitization to drugs. Results In the short-term treated group, median HGF AUCss, Cmax and Caverage were about four-fold that of the control group, whereas Cmin was three-fold. In the patients treated chronically median HGF serum levels rose about six-fold in the first week, and decreased but remained significantly higher after one month. The pharmacokinetic of nadroparin-dependent HGF increase were similar in the two groups. The HGF concentrations measured after both acute and chronic treatment were found to be effective in sensitising ovarian cancer cells to chemotherapeutics. Conclusions This study raises the possibility of using LMWH to increase HGF serum concentration and to take advantage of its biological activities. In particular, nadroparin might be used as a chemo-potentiating agent in epithelial cell ovarian carcinoma through its action on HGF serum concentration. Trial registration ClinicalTrials.gov ID: NCT01523652</p

COVID-19, anosmia, and ageusia in atopic children

: More than a year and a half after the beginning of the coronavirus disease 2019 (COVID-19) pandemic, symptoms, such as loss of smell and taste (anosmia and ageusia, respectively), remain difficult to characterize and quantify, especially in children, since no validated tests to assess these disorders are available. However, these symptoms can also be seen in children, although less frequently than observed in the adult population. In this article, we present the results of a national survey that collected the responses of 267 Italian pediatricians on the presence of anosmia and ageusia in children affected by COVID-19. These data were then compared with existing literature