Detection of Alzheimer's Disease using cortical diffusion tensor imaging

The aim of this research was to test a novel in-vivo brain MRI analysis method that could be used in clinical cohorts to investigate cortical architecture changes in patients with Alzheimer's Disease (AD). Three cohorts of patients with probable AD and healthy volunteers were used to assess the results of the method. The first group was used as the “Discovery” cohort, the second as the “Test” cohort and the last “ATN” (Amyloid, Tau, Neurodegeneration) cohort was used to test the method in an ADNI 3 cohort, comparing to amyloid and Tau PET. The method can detect altered quality of cortical grey matter in AD patients, providing an additional tool to assess AD, distinguishing between these and healthy controls with an accuracy range between good and excellent. These new measurements could be used within the “ATN” framework as an index of cortical microstructure quality and a marker of Neurodegeneration. Further development may aid diagnosis, patient selection, and quantification of the “Neurodegeneration” component in response to therapies in clinical trials

Using diffusion tensor imaging to detect cortical changes in fronto-temporal dementia subtypes

Fronto-temporal dementia (FTD) is a common type of presenile dementia, characterized by a heterogeneous clinical presentation that includes three main subtypes: behavioural-variant FTD, non-fluent/agrammatic variant primary progressive aphasia and semantic variant PPA. To better understand the FTD subtypes and develop more specific treatments, correct diagnosis is essential. This study aimed to test the discrimination power of a novel set of cortical Diffusion Tensor Imaging measures (DTI), on FTD subtypes. A total of 96 subjects with FTD and 84 healthy subjects (HS) were included in the study. A “selection cohort” was used to determine the set of features (measurements) and to use them to select the “best” machine learning classifier from a range of seven main models. The selected classifier was trained on a “training cohort” and tested on a third cohort (“test cohort”). The classifier was used to assess the classification power for binary (HS vs. FTD), and multiclass (HS and FTD subtypes) classification problems. In the binary classification, one of the new DTI features obtained the highest accuracy (85%) as a single feature, and when it was combined with other DTI features and two other common clinical measures (grey matter fraction and MMSE), obtained an accuracy of 88%. The new DTI features can distinguish between HS and FTD subgroups with an accuracy of 76%. These results suggest that DTI measures could support differential diagnosis in a clinical setting, potentially improve efficacy of new innovative drug treatments through effective patient selection, stratification and measurement of outcomes

Brain connectivity changes in autosomal recessive Parkinson Disease: a model for the sporadic form

Biallelic genetic mutations in the Park2 and PINK1 genes are frequent causes of autosomal recessive PD. Carriers of single heterozygous mutations may manifest subtle signs of disease, thus providing a unique model of preclinical PD. One emerging hypothesis suggests that non-motor symptom of PD, such as cognitive impairment may be due to a distributed functional disruption of various neuronal circuits. Using resting-state functional MRI (RS-fMRI), we tested the hypothesis that abnormal connectivity within and between brain networks may account for the patients' cognitive status. Eight homozygous and 12 heterozygous carriers of either PINK1 or Park2 mutation and 22 healthy controls underwent RS-fMRI and cognitive assessment. RS-fMRI data underwent independent component analysis to identify five networks of interest: default-mode network, salience network, executive network, right and left fronto-parietal networks. Functional connectivity within and between each network was assessed and compared between groups. All mutation carriers were cognitively impaired, with the homozygous group reporting a more prominent impairment in visuo-spatial working memory. Changes in functional connectivity were evident within all networks between homozygous carriers and controls. Also heterozygotes reported areas of reduced connectivity when compared to controls within two networks. Additionally, increased inter-network connectivity was observed in both groups of mutation carriers, which correlated with their spatial working memory performance, and could thus be interpreted as compensatory. We conclude that both homozygous and heterozygous carriers exhibit pathophysiological changes unveiled by RS-fMRI, which can account for the presence/severity of cognitive symptom

Repercussions of the COVID-19 pandemic on child and adolescent mental health: A matter of concern—A joint statement from EAP and ECPCP

COVID-19 pandemic and the consequent rigid social distancing measures implemented, including school closures, have heavily impacted children's and adolescents' psychosocial wellbeing, and their mental health problems significantly increased. However, child and adolescent mental health were already a serious problem before the Pandemic all over the world. COVID-19 is not just a pandemic, it is a syndemic and mentally or socially disadvantaged children and adolescents are the most affected. Non-Communicable Diseases (NCDs) and previous mental health issues are an additional worsening condition. Even though many countries have responded with decisive efforts to scale-up mental health services, a more integrated and community-based approach to mental health is required. EAP and ECPCP makes recommendations to all the stakeholders to take action to promote, protect and care for the mental health of a generation

Relating diffusion tensor imaging measurements to microstructural quantities in the cerebral cortex in multiple sclerosis

To investigate whether the observed anisotropic diffusion in cerebral cortex may reflect its columnar cytoarchitecture and myeloarchitecture, as a potential biomarker for disease-related changes, we compared postmortem diffusion magnetic resonance imaging scans of nine multiple sclerosis brains with histology measures from the same regions. Histology measurements assessed the cortical minicolumnar structure based on cell bodies and associated axon bundles in dorsolateral prefrontal cortex (Area 9), Heschl's gyrus (Area 41), and primary visual cortex (V1). Diffusivity measures included mean diffusivity, fractional anisotropy of the cortex, and three specific measures that may relate to the radial minicolumn structure: the angle of the principal diffusion direction in the cortex, the component that was perpendicular to the radial direction, and the component that was parallel to the radial direction. The cellular minicolumn microcircuit features were correlated with diffusion angle in Areas 9 and 41, and the axon bundle features were correlated with angle in Area 9 and to the parallel component in V1 cortex. This may reflect the effect of minicolumn microcircuit organisation on diffusion in the cortex, due to the number of coherently arranged membranes and myelinated structures. Several of the cortical diffusion measures showed group differences between MS brains and control brains. Differences between brain regions were also found in histology and diffusivity measurements consistent with established regional variation in cytoarchitecture and myeloarchitecture. Therefore, these novel measures may provide a surrogate of cortical organisation as a potential biomarker, which is particularly relevant for detecting regional changes in neurological disorders

Pediatric antibiotic stewardship programs in Europe: a pilot survey among delegates of The European Academy of Pediatrics

BackgroundAntimicrobial resistance (AMR) is one of the leading causes of morbidity and mortality worldwide. Efforts to promote the judicious use of antibiotics and contain AMR are a priority of several medical organizations, including the WHO. One effective way to achieve this goal is the deployment of antibiotic stewardship programs (ASPs). This study aimed to survey the current situation of pediatric ASPs in European countries and establish a baseline for future attempts to harmonize pediatric ASPs and antibiotic use in Europe.MethodsA web-based survey was conducted among national delegates of the European Academy of Paediatrics (EAP). The survey assessed the presence of pediatric ASPs in the representatives’ countries in the inpatient and outpatient settings, the staff included in the programs, and their detailed activities regarding antibiotic use.ResultsOf the 41 EAP delegates surveyed, 27 (66%) responded. Inpatient pediatric ASPs were reported in 74% (20/27) countries, and outpatient programs in 48% (13/27), with considerable variability in their composition and activities. Guidelines for managing pediatric infectious diseases were available in nearly all countries (96%), with those for neonatal infections (96%), pneumonia (93%), urinary tract (89%), peri-operative (82%), and soft tissue (70%) infections being the most common. Pediatric ASPs were reported at the national (63%), institutional (41%), and regional/local (<15%) levels. Pediatricians with infectious disease training (62%) and microbiologists (58%) were the most common members of the program personnel, followed by physician leaders (46%), infectious disease/infection control physicians (39%), pharmacists (31%), and medical director representatives (15%). Activities of the pediatric ASPs included educational programs (85%), monitoring and reporting of antibiotic use (70%) and resistance (67%), periodic audits with feedback (44%), prior approval (44%), and post-prescription review of selected antibiotic agents (33%).ConclusionAlthough pediatric ASPs exist in most European countries, their composition and activities vary considerably across countries. Initiatives to harmonize comprehensive pediatric ASPs across Europe are needed

Brain and blood biomarkers of tauopathy and neuronal injury in humans and rats with neurobehavioral syndromes following blast exposure

Traumatic brain injury (TBI) is a risk factor for the later development of neurodegenerative diseases that may have various underlying pathologies. Chronic traumatic encephalopathy (CTE) in particular is associated with repetitive mild TBI (mTBI) and is characterized pathologically by aggregation of hyperphosphorylated tau into neurofibrillary tangles (NFTs). CTE may be suspected when behavior, cognition, and/or memory deteriorate following repetitive mTBI. Exposure to blast overpressure from improvised explosive devices (IEDs) has been implicated as a potential antecedent for CTE amongst Iraq and Afghanistan Warfighters. In this study, we identified biomarker signatures in rats exposed to repetitive low-level blast that develop chronic anxiety-related traits and in human veterans exposed to IED blasts in theater with behavioral, cognitive, and/or memory complaints. Rats exposed to repetitive low-level blasts accumulated abnormal hyperphosphorylated tau in neuronal perikarya and perivascular astroglial processes. Using positron emission tomography (PET) and the [18F]AV1451 (flortaucipir) tau ligand, we found that five of 10 veterans exhibited excessive retention of [18F]AV1451 at the white/gray matter junction in frontal, parietal, and temporal brain regions, a typical localization of CTE tauopathy. We also observed elevated levels of neurofilament light (NfL) chain protein in the plasma of veterans displaying excess [18F]AV1451 retention. These findings suggest an association linking blast injury, tauopathy, and neuronal injury. Further study is required to determine whether clinical, neuroimaging, and/or fluid biomarker signatures can improve the diagnosis of long-term neuropsychiatric sequelae of mTBI

Management of cryptorchidism: a survey of clinical practice in Italy

<p>Abstract</p> <p>Background</p> <p>An evidence-based Consensus on the treatment of undescended testis (UT) was recently published, recommending to perform orchidopexy between 6 and 12 months of age, or upon diagnosis and to avoid the use of hormones. In Italy, current practices on UT management are little known. Our aim was to describe the current management of UT in a cohort of Italian children in comparison with the Consensus guidelines. As management of retractile testis (RT) differs, RT cases were described separately.</p> <p>Methods</p> <p>Ours is a retrospective, multicenter descriptive study. An online questionnaire was filled in by 140 Italian Family Paediatricians (FP) from <it>Associazione Culturale Pediatri </it>(ACP), a national professional association of FP. The questionnaire requested information on all children with cryptorchidism born between 1/01/2004 and 1/01/2006. Data on 169 children were obtained. Analyses were descriptive.</p> <p>Results</p> <p>Overall 24% of children were diagnosed with RT, 76% with UT. Among the latter, cryptorchidism resolved spontaneously in 10% of cases at a mean age of 21.6 months. Overall 70% of UT cases underwent orchidopexy at a mean age of 22.8 months (SD 10.8, range 1.2-56.4), 13% of whom before 1 year. The intervention was performed by a paediatric surgeon in 90% of cases, with a success rate of 91%. Orchidopexy was the first line treatment in 82% of cases, while preceded by hormonal treatment in the remaining 18%. Hormonal treatment was used as first line therapy in 23% of UT cases with a reported success rate of 25%. Overall, 13 children did not undergo any intervention (mean age at last follow up 39.6 months). We analyzed the data from the 5 Italian Regions with the largest number of children enrolled and found a statistically significant regional difference in the use of hormonal therapy, and in the use of and age at orchidopexy.</p> <p>Conclusions</p> <p>Our study showed an important delay in orchidopexy. A quarter of children with cryptorchidism was treated with hormonal therapy. In line with the Consensus guidelines, surgery was carried out by a paediatric surgeon in the majority of cases, with a high success rate.</p

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe