Trajectories and predictors of growth and neurodevelopment in Very Low Birth Weight infants

Neurodevelopment of preterm children has become an outcome of major interest since the improvement in survival due to advances in neonatal care. Many studies focused on the relationships among prenatal characteristics and neurodevelopmental outcome in order to identify the higher risk preterms’ subgroups. The aim of this study is to analyze and put in relation growth and development trajectories to investigate their association. 346 children born at the S.Orsola Hospital in Bologna from 01/01/2005 to 30/06/2011 with a birth weight of <1500 grams were followed up in a longitudinal study at different intervals from 3 to 24 months of corrected age. During follow-up visits, preterms’ main biometrical characteristics were measured and the Griffiths Mental Development Scale was administered to assess neurodevelopment. Latent Curve Models were developed to estimate the trajectories of length and of neurodevelopment, both separately and combined in a single model, and to assess the influence of clinical and socio-economic variables. Neurodevelopment trajectory was stepwise declining over time and length trajectory showed a steep increase until 12 months and was flat afterwards. Higher initial values of length were correlated with higher initial values of neurodevelopment and predicted a more declining neurodevelopment. SGA preterms and those from families with higher status had a less declining neurodevelopment slope, while being born from a migrant mother proved negative on neurodevelopment through the mediating effect of a being taller at 3 months. A longer stay in NICU used as a proxy of preterms’ morbidity) was predictive of lower initial neurodevelopment levels. At 24 months, neurodevelopment is more similar among preterms and is more accurately evaluated. The association among preterms’ neurodevelopment and physiological growth may provide further insights on the determinants of preterms’ outcomes. Sound statistical methods, exploiting all the information collected in a longitudinal study, may be more appropriate to the analysis

Small-scale spatial distribution of COVID-19-related excess mortality

Mortality due to massive events like the COVID-19 pandemic is underestimated because of several reasons, among which the impossibility to track all positive cases and the inadequacy of coding systems are presumably the most relevant. Therefore, the most affordable method to estimate COVID-19-related mortality is excess mortality (EM). Very often, though, EM is calculated on large spatial units that may entail different EM patterns and without stratifying deaths by age or sex, while, especially in the case of epidemics, it is important to identify the areas that suffered a higher death toll or that were spared. We developed the Stata COVID19_EM.ado procedure that estimates EM within municipalities in six subgroups defined by sex and age class using official data provided by ISTAT (Italian National Statistics Bureau) on deaths occurred from 2015 to 2020. Using simple linear regression models, we estimated the mortality trend in each age-and-sex subgroup and obtained the expected deaths of 2020 by extrapolating the linear trend. The results are then displayed using choropleth maps. Subsequently, local autocorrelation maps, which allow to appreciate the presence of local clusters of high or low EM, may be obtained using an R procedure that we developed.We focused on estimating excess mortality in small-scale spatial units (municipalities) and in population strata defined by age and sex.This method gives a deeper insight on excess mortality than summary figures at regional or national level, enabling to identify the local areas that suffered the most and the high-risk population subgroups within them.This type of analysis could be replicated on different time frames, which might correspond to successive epidemic waves, as well as to periods in which containment measures were enforced and for different age classes; moreover, it could be applied in every instance of mortality crisis within a region or a country. (C) 2021 Published by Elsevier B.V

Measuring costs of community mental health care in Italy: A prevalence-based study

AbstractBackground:Information on individual mental healthcare costs and utilization patterns in Italy is scant. We analysed the use and the annual costs of community mental health services (MHS) in an Italian local health authority (LHA). Our aims are to compare the characteristics of patients in the top decile of costs with those of the remaining 90%, and to investigate the demographic and clinical determinants of costs.Methods:This retrospective study is based on administrative data of adult patients with at least one contact with MHS in 2013. Costs of services were estimated using a microcosting method. We defined as high cost (HC) those patients whose community mental health services costs place them in the top decile of the cost distribution. The predictors of costs were investigated using multiple linear regression.Results:The overall costs borne for 7601 patients were 17 million €, with HC accounting for 87% of costs and 73% of services. Compared with the rest of the patients, HC were younger, more likely to be male, to have a diagnosis of psychosis, and longer and more intensive MHS utilization. In multiple linear regression, younger age, longer duration of contact with MHS, psychosis, bipolar disorder, personality disorder, depression, dementia and Italian citizenship accounted for 20.7% of cost variance.Conclusion:Direct mental health costs are concentrated among a small fraction of patients who receive intensive socio-rehabilitation in community services. One limitation includes the unavailability of hospital costs. Our methodology is replicable and useful for national and cross-national benchmarking

Describing communication profiles of low-risk preterm and full-term late talkers

Introduction: Late talkers represent a heterogeneous population. We aimed to describe communication profiles of low-risk preterm and full-term late talkers according to their receptive and expressive vocabulary size, considering communicative, linguistic, cognitive, and motor skills, as well as biological and environmental risk factors. Methods: Sixty-eight late talkers (33 born low-risk preterm and 35 full-term) were identified through a language screening at 30 months. Parents filled out the Italian Short Forms of the MacArthur Bates Communicative Development Inventories and the Socio Conversational Skills Rating Scales. Children were assessed with the Picture Naming Game test and the Bayley Scales of Infant and Toddler Development. Results: A two-step cluster analysis identified three distinct profiles among late talkers according to their receptive and expressive vocabulary size. Severe late talkers (25%) showed less frequent use of pointing, limited verbal imitation, receptive vocabulary size, lexical and sentence production, responsiveness and assertiveness, and lower cognitive scores than mild late talkers (40%). Moderate late talkers (35%) showed less frequent verbal imitation, limited lexical and sentence production and lower cognitive scores than mild late talkers. Male gender was significantly more represented in the severe late profile, whereas other biological and environmental factors did not differ among the three profiles. Conclusions: Findings highlighted the relevance of assessing communicative, lexical, grammar, pragmatic, and cognitive skills to describe late talkers’ profiles. A deeper investigation of phonological skills might also contribute to a further understanding of interindividual variability in this population

Intron 4-5 hTERT DNA Hypermethylation in Merkel Cell Carcinoma: Frequency, Association with Other Clinico-pathological Features and Prognostic Relevance

Merkel cell carcinoma (MCC) is an aggressive skin tumor with neuroendocrine differentiation, mainly affecting elderly population or immunocompromised individuals. As methylation of the human telomerase reverse transcriptase (mhTERT) has been shown to be a prognostic factor in different tumors, we investigated its role in MCC, in particular in intron 4-5 where rs10069690 has been mapped and recognized as a cancer susceptibility locus. DNA methylation analysis of hTERT gene was assessed retrospectively in a cohort of 69 MCC patients from the University of Bologna, University of Turin and University of Insubria. Overall mortality was evaluated with Kaplan-Meier curves and multivariable Royston-Parmar models. High levels of mhTERT (mhTERThigh) (HR\u2009=\u20092.500, p\u2009=\u20090.015) and p63 (HR\u2009=\u20092.659, p\u2009=\u20090.016) were the only two clinico-pathological features significantly associated with a higher overall mortality at the multivariate analysis. We did not find different levels of mhTERT between MCPyV (+) and (-) cases (21 vs 14, p\u2009=\u20090.554); furthermore, mhTERThigh was strongly associated with older age (80.5 vs 72&nbsp;years, p\u2009=\u20090.026), no angioinvasion (40.7% vs 71.0%, p\u2009=\u20090.015), lower Ki67 (50 vs 70%, p\u2009=\u20090.005), and PD-L1 expressions in both tumor (0 vs 3%, p\u2009=\u20090.021) and immune cells (0 vs 10%, p\u2009=\u20090.002). mhTERT is a frequently involved epigenetic mechanism and a relevant prognostic factor in MCC. In addition, it belongs to the shared oncogenic pathways of MCC (MCPyV and UV-radiations) and it could be crucial, together with other epigenetic and genetic mechanisms as gene amplification, in determining the final levels of hTERT mRNA and telomerase activity in these patients

Insight in cognitive impairment assessed with the Cognitive Assessment Interview in a large sample of patients with schizophrenia

The Cognitive Assessment Interview (CAI) is an interview-based scale measuring cognitive impairment and its impact on functioning in subjects with schizophrenia (SCZ). The present study aimed at assessing, in a large sample of SCZ (n = 601), the agreement between patients and their informants on CAI ratings, to explore patients' insight in their cognitive deficits and its relationships with clinical and functional indices. Agreement between patient- and informant-based ratings was assessed by the Gwet's agreement coefficient. Predictors of insight in cognitive deficits were explored by stepwise multiple regression analyses. Patients reported lower severity of cognitive impairment vs. informants. A substantial to almost perfect agreement was observed between patients' and informants' ratings. Lower insight in cognitive deficits was associated to greater severity of neurocognitive impairment and positive symptoms, lower severity of depressive symptoms, and older age. Worse real-life functioning was associated to lower insight in cognitive deficit, worse neurocognitive performance, and worse functional capacity. Our findings indicate that the CAI is a valid co-primary measure with the interview to patients providing a reliable assessment of their cognitive deficits. In the absence of informants with good knowledge of the subject, the interview to the patient may represent a valid alternative

Lipid profile in Noonan syndrome and related disorders: trend by age, sex and genotype

BackgroundRASopathies are developmental disorders caused by dysregulation of the RAS-MAPK signalling pathway, which contributes to the modulation of multiple extracellular signals, including hormones and growth factors regulating energetic metabolism, including lipid synthesis, storage, and degradation.Subjects and methodsWe evaluated the body composition and lipid profiles of a single-centre cohort of 93 patients with a molecularly confirmed diagnosis of RASopathy by assessing height, BMI, and total cholesterol, HDL, triglycerides, apolipoprotein, fasting glucose, and insulin levels, in the context of a cross sectional and longitudinal study. We specifically investigated and compared anthropometric and haematochemistry data between the Noonan syndrome (NS) and Mazzanti syndrome (NS/LAH) groups.ResultsAt the first evaluation (9.5 ± 6.2 years), reduced growth (-1.80 ± 1.07 DS) was associated with a slightly reduced BMI (-0.34 DS ± 1.15 DS). Lipid profiling documented low total cholesterol levels (&lt; 5th percentile) in 42.2% of the NS group; in particular, in 48.9% of PTPN11 patients and in 28.6% of NS/LAH patients compared to the general population, with a significant difference between males and females. A high proportion of patients had HDL levels lower than the 26th percentile, when compared to the age- and sex-matched general population. Triglycerides showed an increasing trend with age only in NS females. Genotype-phenotype correlations were also evident, with particularly reduced total cholesterol in about 50% of patients with PTPN11 mutations with LDL-C and HDL-C tending to decrease during puberty. Similarly, apolipoprotein A1 and apolipoprotein B deficits were documented, with differences in prevalence associated with the genotype for apolipoprotein A1. Fasting glucose levels and HOMA-IR were within the normal range.ConclusionThe present findings document an unfavourable lipid profile in subjects with NS, in particular PTPN11 mutated patients, and NS/LAH. Further studies are required to delineate the dysregulation of lipid metabolism in RASopathies more systematically and confirm the occurrence of previously unappreciated genotype-phenotype correlations involving the metabolic profile of these disorders

Kinetics of cytomegalovirus and Epstein-Barr virus DNA in whole blood and plasma of kidney transplant recipients: Implications on management strategies

This retrospective multicenter cohort study investigated the kinetics (ascending and descending phases) of cytomegalovirus (CMV) and Epstein-Barr virus (EBV)-DNA in whole blood (WB) and plasma samples collected from adult kidney transplant (KT) recipients. CMV-DNA kinetics according to antiviral therapy were investigated. Three hundred twenty-eight paired samples from 42 episodes of CMV infection and 157 paired samples from 26 episodes of EBV infection were analyzed by a single commercial molecular method approved by regulatory agencies for both matrices. CMV-DNAemia followed different kinetics in WB and plasma. In the descending phase of infection, a slower decay of viral load and a higher percentage of CMV-DNA positive samples were observed in plasma versus WB. In the 72.4% of patients receiving antiviral therapy, monitoring with plasma CMV-DNAemia versus WB CMV-DNAemia could delay treatment interruption by 7-14 days. Discontinuation of therapy based on WB monitoring did not result in relapsed infection in any patients. Highly different EBV-DNA kinetics in WB and plasma were observed due to lower positivity in plasma; EBV positive samples with a quantitative result in both blood compartments were observed in only 11.5% of cases. Our results emphasize the potential role of WB as specimen type for post-KT surveillance of both infections for disease prevention and management

Relationship between immune response to SARS-CoV2 vaccines and development of breakthrough infection in solid organ transplant recipients: the CONTRAST cohort

Background: SARS-CoV-2 vaccination in solid organ transplant (SOT) is associated with poorer antibody response (AbR) compared to non-SOT recipients. However, its impact on the risk of breakthrough infection (BI) should yet be assessed. Methods: Single-center prospective longitudinal cohort study enrolling adult SOT recipients who received SARS-CoV2 vaccination during 1-year period from February 2021, and followed-up to April 30th 2022. Patients were tested for AbR at multiple timepoints. Primary endpoint was BI (laboratory confirmed SARS-CoV2 infection ≥14 days after 2nd dose). Immunization (positive AbR) was considered an intermediate state between vaccination and BI. Probabilities of being in vaccination, immunization and BI states were obtained for each type of graft and vaccination sequence with multistate survival analysis, then multivariable logistic regression was performed to analyse the risk of BI in AbR levels. Results: 614 SOT (275 kidney, 163 liver, 137 heart, 39 lung) recipients were included. Most patients (84.7%) received three vaccine doses, the first two consisted of BNT162b2 and mRNA-1273 in 73.5% and 26.5% of cases, respectively; while at the third dose mRNA-1273 was administered in 59.8% of patients. Overall, 75.4% of patients reached immunization and 18.4% developed BI. Heart transplant recipients showed lowest probability of immunization (0.418) and highest of BI (0.323), all-mRNA-1273 vaccine-sequence showed higher probability of immunization (0.732) and lowest of BI (0.098). Risk of BI was higher for non-high-level AbR, younger age and shorter time from transplant. Conclusions: SOT patients with non-high-level AbR, shorter time from transplantation, and heart recipients are at highest risk of BI

Universal Newborn Screening for Congenital Cytomegalovirus Infection - From Infant to Maternal Infection: A Prospective Multicenter Study

Introduction: Most infants at risk for cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) are unrecognized because of the absence of a universal neonatal CMV screening. The search of CMV-DNA by molecular methods in salivary swabs was demonstrated to be a reliable approach. This study describes the results obtained by carrying out a universal screening for congenital CMV (cCMV) infection including all live-born newborns in three Italian sites, as well as the therapeutic interventions and clinical outcome of the CMV-infected neonates. Moreover, CMV maternal infection's characteristics were evaluated. Methods: To confirm or exclude cCMV infection, a CMV-DNA-positive result on a first salivary swab was followed by repeated saliva and urine samples collected within 21 days of age. Breast milk samples were also collected. The search of CMV-DNA was performed with a single automated quantitative commercial real-time PCR assay, regardless of the type of samples used. Results: A total of 3,151 newborns were enrolled; 21 (0.66%) of them were congenitally infected (median saliva viral load at screening, 6.65 [range, 5.03-7.17] log10 IU/ml). Very low/low viral load in screening saliva samples (median value, 1.87 [range, 1.14-2.59] log10 IU/ml) was associated with false-positive results (n = 54; 1.7%). CMV-DNA was detected in almost half of the breast milk samples of mother-infant pairs with a false-positive result, suggesting that contamination from breast milk may not be the only explanation in the study population. cCMV infection confirmation with the search of CMV-DNA in a urine sample proved to be the gold standard strategy, since false-positive results were observed in 4/54 (7.5%) of the repeated saliva samples. Symptomatic cCMV infection was observed in 3/21 (14.3%) infants; notably, one (4.7%) developed moderate unilateral SNHL at 5 months after birth. Finally, two symptomatic cCMV infections were associated with primary maternal infection acquired in the first trimester of gestation; one newborn with severe cCMV symptoms was born to a mother with no CMV checkups in pregnancy. Conclusion: Without universal neonatal CMV screening, some infected infants who develop late neurological sequelae may not be recognized and, consequently, they are not able to benefit early from instrumental and therapeutic interventions to limit and/or treat CMV disease