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Identification of clinical phenotypes in chronic obstructive pulmonary disease (COPD) patients could be useful for associating disease attributes with clinically meaningful outcomes in order to develop more specific treatments that are targeted to various patient subgroups. To have the greatest clinical impact, the definition of a phenotype should be related as strictly as possible to predominant pathogenetic mechanisms of expiratory airflow limitation. To this end, analysis of chest computerized tomography (CT) data has become the reference standard for the investigation of the correlation between the pathologic changes in the airways and parenchyma and other clinical, functional, and chest radiographic data. This in vivo evaluation has been useful in confirming the heterogeneity of the disorder and differentiating patients presenting with very different characteristics. The identification of the two most significant pathogenetic mechanisms of airflow limitation led to the characterization of the two phenotypes: patients with predominant airway obstruction and patients with predominant emphysematous destruction. In spite of the continuing effort with the goal of understanding the various clinical presentations of COPD on the basis of pathogenetic mechanisms and structural changes detected on CT scan, future studies are still needed to aid in developing a reliable model for predicting the phenotype and developing targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Autoimmune encephalitis is a relatively novel nosological entity characterized by an immune-mediated damage of the central nervous system. While originally described as a paraneoplastic inflammatory phenomenon affecting limbic structures, numerous instances of non-paraneoplastic pathogenesis, as well as extra-limbic involvement, have been characterized. Given the wide spectrum of insidious clinical presentations ranging from cognitive impairment to psychiatric symptoms or seizures, it is crucial to raise awareness about this disease category. In fact, an early diagnosis can be dramatically beneficial for the prognosis both to achieve an early therapeutic intervention and to detect a potential underlying malignancy. In this scenario, the radiologist can be the first to pose the hypothesis of autoimmune encephalitis and refer the patient to a comprehensive diagnostic work-up – including clinical, serological, and neurophysiological assessments.In this article, we illustrate the main radiological characteristics of autoimmune encephalitis and its subtypes, including the typical limbic presentation, the features of extra-limbic involvement, and also peculiar imaging findings. In addition, we review the most relevant alternative diagnoses that should be considered, ranging from other encephalitides to neoplasms, vascular conditions, and post-seizure alterations. Finally, we discuss the most appropriate imaging diagnostic work-up, also proposing a suggested MRI protocol. [ABSTRACT FROM AUTHOR]

Purpose: Psychosis is a symptom common to several mental illnesses and a defining feature of schizophrenia spectrum disorders, whose onset typically occurs in adolescence. Neuroradiological studies have reported evidence of brain structural abnormalities in patients with overt psychosis. However, early identification of brain structural changes in young subjects at risk for developing psychosis (such as those with Attenuated Psychosis Syndrome –APS) is currently lacking. Methods: Brain 3D T1-weighted and 64 directions diffusion-weighted images were acquired on 55 help-seeking adolescents (12–17 years old) with psychiatric disorders who referred to our Institute. Patients were divided into three groups: non-APS (n = 20), APS (n = 20), and Early-Onset Psychosis (n = 15). Cortical thickness was calculated from T1w images, and Tract-Based Spatial Statistics analysis was performed to study the distribution of white matter fractional anisotropy and all diffusivity metrics. A thorough neuropsychological test battery was adopted to investigate cognitive performance in several domains. Results: In patients with Attenuated Psychotic Syndrome, the left superior frontal gyrus was significantly thinner compared to patients with non-APS (p = 0.048), and their right medial orbitofrontal cortex thickness was associated with lower working memory scores (p = 0.0025, r = -0.668 for the working memory index and p = 0.001, r = -0.738 for the digit span). Early-Onset Psychosis patients showed thinner left pars triangularis compared to non-APS individuals (p = 0.024), and their left pars orbitalis was associated with impaired performance at the symbol search test (p = 0.005, r = -0.726). No differences in diffusivity along main tracts were found between sub-groups (p > 0.05). Conclusion: This study showed specific associations between structural imaging features and cognitive performance in patients with APS. Characterizing this disorder using neuroimaging could reveal useful information that may aid in the development and evaluation of preventive strategies in these individuals. [ABSTRACT FROM AUTHOR]

Background: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. Methods: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. Results: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. Conclusions: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition. [ABSTRACT FROM AUTHOR]

• Deep learning technique for fast MR parameters mapping of several neuromuscular disorders. • We developed a physics informed neural NetwOrk Myo-DINO for MR parameters mapping enhancing explainability of the learning process. • Myo-DINO accurately reconstructed fat Fraction, water T2 and B1 parameters maps. • Myo-DINO allowed for accelerated and effective parameters prediction of several lower limbs muscles. Magnetic Resonance (MR) parameters mapping in muscle Magnetic Resonance Imaging (mMRI) is predominantly performed using pattern recognition-based algorithms, which are characterised by high computational costs and scalability issues in the context of multi-parametric mapping. Deep Learning (DL) has been demonstrated to be a robust and efficient method for rapid MR parameters mapping. However, its application in mMRI domain to investigate Neuromuscular Disorders (NMDs) has not yet been explored. In addition, data-driven DL models suffered in interpretation and explainability of the learning process. We developed a Physics Informed Neural Network called Myo-Regressor Deep Informed Neural NetwOrk (Myo-DINO) for efficient and explainable Fat Fraction (FF), water-T 2 (wT 2) and B1 mapping from a cohort of NMDs.A total of 2165 slices (232 subjects) from Multi-Echo Spin Echo (MESE) images were selected as the input dataset for which FF, wT 2 ,B1 ground truth maps were computed using the MyoQMRI toolbox. This toolbox exploits the Extended Phase Graph (EPG) theory with a two-component model (water and fat signal) and slice profile to simulate the signal evolution in the MESE framework. A customized U-Net architecture was implemented as the Myo-DINO architecture. The squared L 2 norm loss was complemented by two distinct physics models to define two 'Physics-Informed' loss functions: Cycling Loss 1 embedded a mono-exponential model to describe the relaxation of water protons, while Cycling Loss 2 incorporated the EPG theory with slice profile to model the magnetization dephasing under the effect of gradients and RF pulses. The Myo-DINO was trained with the hyperparameter value of the 'Physics-Informed' component held constant, i.e. λ model = 1, while different hyperparameter values (λ cnn) were applied to the squared L 2 norm component in both the cycling loss. In particular, hard (λ cnn =10), normal (λ cnn =1) and self-supervised (λ cnn =0) constraints were applied to gradually decrease the impact of the squared L 2 norm component on the 'Physics Informed' term during the Myo-DINO training process. Myo-DINO achieved higher performance with Cycling Loss 2 for FF, wT 2 and B1 prediction. In particular, high reconstruction similarity and quality (Structural Similarity Index > 0.92, Peak Signal to Noise ratio > 30.0 db) and small reconstruction error (Normalized Root Mean Squared Error < 0.038) to the reference maps were shown with self-supervised weighting of the Cycling Loss 2. In addition muscle-wise FF, wT 2 and B1 predicted values showed good agreement with the reference values. The Myo-DINO has been demonstrated to be a robust and efficient workflow for MR parameters mapping in the context of mMRI. This provides preliminary evidence that it can be an effective alternative to the reference post-processing algorithm. In addition, our results demonstrate that Cycling Loss 2, which incorporates the Extended Phase Graph (EPG) model, provides the most robust and relevant physical constraints for Myo-DINO in this multi-parameter regression task. The use of Cycling Loss 2 with self-supervised constraint improved the explainability of the learning process because the network acquired domain knowledge solely in accordance with the assumptions of the EPG model. [ABSTRACT FROM AUTHOR]

Objective: Identification of brain regions susceptible to quantifiable atrophy in sporadic Creutzfeldt‐Jakob disease (sCJD) should allow for improved understanding of disease pathophysiology and development of structural biomarkers that might be useful in future treatment trials. Although brain atrophy is not usually present by visual assessment of MRIs in sCJD, we assessed whether using voxel‐based morphometry (VBM) can detect group‐wise brain atrophy in sCJD. Methods: 3T brain MRI data were analyzed with VBM in 22 sCJD participants and 26 age‐matched controls. Analyses included relationships of regional brain volumes with major clinical variables and dichotomization of the cohort according to expected disease duration based on prion molecular classification (i.e., short‐duration/Fast‐progressors (MM1, MV1, and VV2) vs. long‐duration/Slow‐progressors (MV2, VV1, and MM2)). Structural equation modeling (SEM) was used to assess network‐level interactions of atrophy between specific brain regions. Results: sCJD showed selective atrophy in cortical and subcortical regions overlapping with all but one region of the default mode network (DMN) and the insulae, thalami, and right occipital lobe. SEM showed that the effective connectivity model fit in sCJD but not controls. The presence of visual hallucinations correlated with right fusiform, bilateral thalami, and medial orbitofrontal atrophy. Interestingly, brain atrophy was present in both Fast‐ and Slow‐progressors. Worse cognition was associated with bilateral mesial frontal, insular, temporal pole, thalamus, and cerebellum atrophy. Interpretation: Brain atrophy in sCJD preferentially affects specific cortical and subcortical regions, with an effective connectivity model showing strength and directionality between regions. Brain atrophy is present in Fast‐ and Slow‐progressors, correlates with clinical findings, and is a potential biomarker in sCJD. [ABSTRACT FROM AUTHOR]

Although the diagnosis of dementia still is primarily based on clinical criteria, neuroimaging is playing an increasingly important role. This is in large part due to advances in techniques that can assist with discriminating between different syndromes. Magnetic resonance imaging remains atthe core of differential diagnosis, with specific patterns of cortical and subcortical changes having diagnostic significance. Recent developments in molecular PET imaging techniques have opened the door for not only antemortem but early, even preclinical, diagnosis of underlying pathology. This is vital, as treatment trials are underway for pharmacological agents with specific molecular targets, and numerous failed trials suggest that earlier treatment is needed. This article provides an overview of classic neuroimaging findings as well as new and cutting-edge research techniques that assist with clinical diagnosis of a range of dementia syndromes, with an emphasis on studies using pathologically proven cases. [ABSTRACT FROM AUTHOR]

Background and Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum., Methods: We devised a new live cell-based assay (CBA) for PLP1-IgG and used it to test 2 cohorts (retrospective exploratory, n = 284; prospective validation, n = 824) of patients with ADDs and controls (n = 177). Patients were classified as MS, neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other ADDs. PLP1-IgG-positive samples were tested for IgG subclasses, DM20-IgG, and on rat brain tissue-based assay (TBA). Complement-dependent cytotoxicity (CDC) was assessed on a live CBA and antigen specificity and conformational binding through immunoadsorption/colocalization/fixation experiments., Results: PLP1-IgG were found in 0 of 177 controls and 42 of 1104 patients with ADDs mainly diagnosed as other ADDs (19/42) with frequent myelitis/encephalomyelitis (14/19) and coexisting PNS involvement (13/19). Four of 19 patients with other ADDs fulfilled the seronegative NMOSD criteria. PLP1-IgG were also found in patients with MOGAD (11/42), more frequently with PNS involvement ( p = 0.01), and in patients with MS (12/42), more frequently with atypical features ( p < 0.001). PLP1-IgG-positive MOGAD had higher EDSS scores ( p < 0.001) and PLP1-IgG-positive MS had higher severity scores (MSSS, p < 0.001) compared with those PLP1-IgG-negative. Overall, PLP1-IgG were found in 24.1% of patients with CNS+PNS-ADD, 21.2% with atypical MS, 8.3% with MOGAD, 12.0% with seronegative NMOSD, and 1.4% with typical MS. Their frequency within each diagnostic subgroup was consistent between the exploratory and validation cohorts. PLP1-IgG a) colocalized with their target on CBA-TBA, where their binding was abolished after immunoadsorption and fixation-induced conformational epitope alteration; b) mostly pertained to the IgG1/IgG3 subclass (68.3%) and were able to induce CDC; and c) coreacted with DM20 in all 12 patients with PNS involvement tested., Discussion: Conformational PLP1-IgG predominantly identify patients with non-MS ADDs. They should be tested mainly in those with CNS + PNS ADD, coherently with DM20-IgG coreactivity. PLP1-IgG could also be investigated as disease modifiers and prognostic markers in MS and MOGAD. Preliminary evidence supports their pathogenic potential.

Objective: To estimate the developmental trends of quantitative parameters obtained from chest computed tomography (CT) and to provide normative values on dimensions of bronchi and arteries, as well as bronchus-artery (BA) ratios from preschool age to young adulthood., Materials and Methods: Two independent radiologists screened a dataset of 1160 chest CT scans, initially reported as normal, from participants aged 0 to 24 years. Using an automated deep learning-based algorithm, we computed the following bronchus and artery parameters: bronchial outer diameter (B out ), bronchial inner diameter (B in ), adjacent pulmonary artery diameter (A), bronchial wall thickness (B wt ), bronchial wall area (B WA ), and bronchial outer area (B OA ). From these parameters, we computed the following ratios: B out /A, B in /A, B wt /A, B wt /B out , and B WA /B OA . Furthermore, mean lung density, total lung volume, and the square root of wall area of bronchi with a 10-mm lumen perimeter (Pi10) were obtained. The effects on CT parameters of age, sex, and iodine contrast were investigated using mixed-effects or regression model analyses., Results: 375 normal inspiratory chest CT scans (females / males = 156 / 219; mean age [SD] 12.7 [5.0] years) met the inclusion criteria. B out and B in progressively increased with age (all p < 0.05), but B wt , B out /A, B in /A, B wt /A, B wt /B out , or B WA /B OA did not. Total lung volume and mean lung density continuously increased with age (both p < 0.001), while Pi10 did not exhibit such a trend. B out , total lung volume, and mean lung density were the only parameters that differed between males and females, all higher in males than females (all p < 0.03). The presence of iodinated contrast led to greater values for B wt , B wt /B out , and B WA /B OA , but lower values for B in , B out /A, B in /A, and B wt /A (all p < 0.01)., Conclusion: Quantitative CT parameters of both lung parenchyma and bronchi exhibit growth-related changes, but from 6 to 24 years ratios between bronchus and artery dimensions remain constant. Contrast-enhanced CT scans affect the assessment of lung parenchyma and bronchial size. We propose age and technique-dependent normative values for bronchial dimensions and wall thickness., Key Points: Question What are the developmental trends of quantitative lung CT parameters in patients from childhood into young adulthood? Findings The ratio between bronchus and pulmonary artery dimensions demonstrates consistent values across age groups, indicating synchronized growth between bronchi and paired pulmonary arteries. Clinical relevance Our findings highlight the importance of standardized CT protocol and volume acquisition, and emphasize the need for ongoing collection of normal chest CT scans to refine the proposed reference values., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Dr. Pierluigi Ciet. Conflict of interest: The author of this manuscript, Harm Tiddens, declares relationships with the following companies: Insmed, TBIO, Thirona, Neupharma and Boehringer. The author of this manuscript, Jean-Paul Charbonnier, declares relationships with Thirona. Daan Caudri is director of the Erasmus MC-LungAnalysis laboratory. The author of this manuscript, Pierluigi Ciet, declares relationships with the following companies: Vertex Pharmaceutical, Chiesi Pharmaceuticals, and Siemens Healthineers. Wieying Kuo is affiliated with Voiant Clinical. The rest of the authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors, Eleni-Rosalina Andrinopoulou, has significant statistical expertise. Informed consent: Written informed consent was not required for this study because this is a retrospective study. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: The cohort has been previously reported in Kuo et al [6]. In the previous study, the dataset consisted of 294 out of 1160 chest CT scans of children and adolescents were collected retrospectively by the international multicenter Normal Chest CT Study Group. The previous study aimed to define normative data on central airway dimensions, in particular trachea, right main bronchi, and left main bronchi, in chest CT of children. On these 294 inspiratory CT scans, central airways were semi-automatically analyzed using Myrian XP-Lung software (version 1.19.1, Intrasense). The intrathoracic tracheal length was measured from the carina to the thorax inlet manually. In the recent study, the dataset consisted of 375 out of 1160 chest CT scans of children and young adults. The primary aim of the current study is to establish normative data for the dimensions of peripheral airways extending down to the 6th bronchial generation, in chest CT of children. On these 375 inspiratory CT scans, bronchi and adjacent pulmonary arteries were automatically analyzed using LungQ (version 2.0.1, Thirona). Using this algorithm, we computed the following bronchus and artery parameters from segmental bronchi to the most peripheral detectable bronchi: bronchial outer diameter (Bout), bronchial inner diameter (Bin), adjacent pulmonary artery diameter (A), bronchial wall thickness (Bwt), bronchial wall area (BWA), and bronchial outer area (BOA). From these parameters, we computed the following ratios: Bout/A, Bin/A, Bwt/A, Bwt/Bout, and BWA/BOA. Furthermore, mean lung density, total lung volume, and the square root of wall area of bronchi with a 10-mm lumen perimeter (Pi10) were obtained by using another module from the same software package. Methodology: Retrospective Observational Multicenter study, (© 2025. The Author(s).)

Grey matter involvement is a well-known feature in sporadic Creutzfeldt-Jakob disease (sCJD), yet precise anatomy-based quantification of reduced diffusivity is still not fully understood. Default Mode Network (DMN) areas have been recently demonstrated as selectively involved in sCJD, and functional connectivity has never been investigated in prion diseases. We analyzed the grey matter involvement using a quantitatively multi-parametric MRI approach. Specifically, grey matter mean diffusivity of 37 subjects with sCJD was compared with that of 30 age-matched healthy controls with a group-wise approach. Differences in mean diffusivity were also examined between the cortical (MM(V)1, MM(V)2C, and VV1) and subcortical (VV2 and MV2K) subgroups of sCJD for those with autopsy data available (n = 27, 73%). We also assessed resting-state functional connectivity of both ventral and dorsal components of DMN in a subset of subject with a rs-fMRI dataset available (n = 17). Decreased diffusivity was predominantly present in posterior cortical regions of the DMN, but also outside of the DMN in temporal areas and in a few limbic and frontal areas, in addition to extensive deep nuclei involvement. Both subcortical and cortical sCJD subgroups showed decreased diffusivity subcortically, whereas only the cortical type expressed significantly decreased diffusivity cortically, mainly in parietal, occipital, and medial-inferior temporal cortices bilaterally. Interestingly, we found abnormally increased connectivity in both dorsal and ventral components of the DMN in sCJD subjects compared with healthy controls. The significance and possible utility of functional imaging as a biomarker for tracking disease progression in prion disease needs to be explored further., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Recently, it has been shown and validated that presence and severity of emphysema on computed tomography could be estimated by a novel spirometry based index, the emphysema severity index (ESI). However, the clinical relevance of the index has not been established. We conducted cox-regression analyses with adjustment for age, smoking, sex, forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) to study whether ESI was associated with all-cause, respiratory and non-respiratory 10-year mortality. Study population was all participants with acceptable spirometry from the Gott Åldrande i Skåne study, a Swedish general population aged 65-102 years old. ESI is expressed as a continuous numeric parameter on a scale ranging from 0 to 10. Out of the 4453 participants in the main study, 3974 was included in the final analysis. Higher age, higher ESI, lower FEV 1 and male sex increased hazard of respiratory death. ESI was significantly correlated to respiratory death but not non-respiratory death, while high age, male sex and low FEV 1 was associated with non-respiratory as well as respiratory death. Current smoking habits increased the hazard of respiratory death but did not reach significance (p 0.066) One unit increase in ESI increased hazard of all-cause death by 20% (p 0.0002) and hazard of respiratory death by 57% (p < 0.0001). The ESI is a novel clinical marker of emphysema severity that is associated with respiratory death specifically. Since it can be derived from standard spirometry there are potential benefits for clinical practice in terms of more individualised prognosis and treatment alternatives., Competing Interests: Declaration of competing interest Dr. Occhipinti reports grants from Fondazione Menarini, personal fees from Novartis, outside the submitted work; Dr. Wollmer reports grants from Swedish Heart and Lung Foundation, grants from Lund University, grants from Skåne Region, during the conduct of the study; personal fees from Chiesi Pharma, outside the submitted work; In addition, Dr. Wollmer has a patent Device and method for pulmonary function measurement issued.. Dr. Luoto reports grants from Skåne County, during the conduct of the study., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: In this study we address the automatic segmentation of selected muscles of the thigh and leg through a supervised deep learning approach., Material and Methods: The application of quantitative imaging in neuromuscular diseases requires the availability of regions of interest (ROI) drawn on muscles to extract quantitative parameters. Up to now, manual drawing of ROIs has been considered the gold standard in clinical studies, with no clear and universally accepted standardized procedure for segmentation. Several automatic methods, based mainly on machine learning and deep learning algorithms, have recently been proposed to discriminate between skeletal muscle, bone, subcutaneous and intermuscular adipose tissue. We develop a supervised deep learning approach based on a unified framework for ROI segmentation., Results: The proposed network generates segmentation maps with high accuracy, consisting in Dice Scores ranging from 0.89 to 0.95, with respect to "ground truth" manually segmented labelled images, also showing high average performance in both mild and severe cases of disease involvement (i.e. entity of fatty replacement)., Discussion: The presented results are promising and potentially translatable to different skeletal muscle groups and other MRI sequences with different contrast and resolution., (© 2021. The Author(s).)

Quantitative muscle MRI (water-T2 and fat mapping) is being increasingly used to assess disease involvement in muscle disorders, while imaging techniques for assessment of the dynamic and elastic muscle properties have not yet been translated into clinics. In this exploratory study, we quantitatively characterized muscle deformation (strain) in patients affected by facioscapulohumeral muscular dystrophy (FSHD), a prevalent muscular dystrophy, by applying dynamic MRI synchronized with neuromuscular electrical stimulation (NMES). We evaluated the quadriceps muscles in 34 ambulatory patients and 13 healthy controls, at 6-to 12-month time intervals. While a subgroup of patients behaved similarly to controls, for another subgroup the median strain decreased over time (approximately 57% over 1.5 years). Dynamic MRI parameters did not correlate with quantitative MRI. Our results suggest that the evaluation of muscle contraction by NMES-MRI is feasible and could potentially be used to explore the elastic properties and monitor muscle involvement in FSHD and other neuromuscular disorders., (© 2022. The Author(s).)

Background: Chronic obstructive pulmonary disease (COPD) is a generic term identifying a condition characterized by variable changes in peripheral airways and lung parenchyma. Standard spirometry cannot discriminate the relative role of conductive airways inflammatory changes from destructive parenchymal emphysema changes. The aim of this study was to quantify the emphysema component in COPD by a simple parameter (the Emphysema Severity Index - ESI), previously proved to reflect CT-assessed emphysema., Methods: ESI was obtained by fitting the descending limb of MEFV curves by a fully automated procedure providing a 0 to 10 score of emphysema severity. ESI was computed in COPD patients enrolled in the CLIMA Study., Results: The vast majority of ESI values ranged from 0 to 4, compatible with no-to-mild/moderate emphysema component. A limited proportion of patients showed ESI values >4, compatible with severe-to-very severe emphysema. ESI values were greatly dispersed within each GOLD class indicating that GOLD classification cannot discriminate emphysema and conductive airways changes in patients with similar airflow limitation. ESI and diffusing capacity (DL CO ) were significantly correlated (p<0.001). However, the great dispersion in their correlation suggests that ESI and DL CO reflect partially different anatomo-functional determinants in COPD., Conclusions: Airflow limitation has heterogenous determinants in COPD. Inflammatory and destructive changes may combine in CT densitometric alterations that cannot be detected by standard spirometry. ESI computation from spirometric data helps to define the prevailing pathogenetic mechanism underlying the measured airflow limitation. ESI could be a reliable advancement to select large samples of patients in clinical or epidemiological trials, and to compare different pharmacological treatments., (©Copyright: the Author(s).)

Objectives: Autosomic recessive mutations in the PIGN gene have been described in less than 30 subjects to date, in whom multiple congenital anomalies combined with severe developmental delay, hypotonia, epileptic encephalopathy, and cerebellar atrophy have been described as crucial features. A clear-cut neuroradiological characterization of this entity, however, is still lacking. We aim to present three pediatric PIGN mutated cases with an in-depth evaluation of their brain abnormalities., Methods: We present the neuroradiological, clinical, and genetic characterization of three Caucasian pediatric subjects with pathogenic/likely pathogenic variants in the PIGN gene revealed by Next Generation Sequencing analysis., Results: We identified three subjects (two siblings, one unrelated case) presenting with encephalopathy with early-onset epilepsy, hypotonia, and severe global developmental delay. No additional severe multiple congenital anomalies were detected. Neuroradiological evaluation showed extensive quantitative reduction of white matter, severe and progressive cortical atrophy, with frontal predominance and an anteroposterior gradient, combined with cerebellar and brainstem atrophy., Conclusions: Our findings broaden and systematize the neuroradiological spectrum of abnormalities in PIGN related encephalopathy. Furthermore, our dataset confirms that mutations in PIGN gene appear to be pan-ethnic and represent an underestimated cause of early-onset encephalopathy., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2021 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing., Methods: We performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts., Results: Of the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1., Conclusions: The detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene ® ), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality., Methods: Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene ® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV 1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined., Results: Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene ® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics., Conclusions: A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop., Competing Interests: The COPDGene® study is funded by National Heart, Lung, and Blood Institute grants U01 HL089897 and U01 HL089856. The COPDGene® study (NCT00608764) is also supported by the COPD Foundation through contributions made to an Industry Advisory Committee comprised of AstraZeneca, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion. While some individual authors of this manuscript were employed by one of the listed funders at the time the work of this study was conducted, these employment relationships did not constitute undue influence by funders. These funders have had no official role in the collection, management, analysis and interpretation of the data or design and conduct of the study. All authors have completed a Conflict of Interest form, disclosing any real or apparent financial relationships including receiving royalties, honoraria or fees for consulting, lectures, speakers’ bureaus, continuing education, medical advisory boards or expert testimony; receipt of grants; travel reimbursement; direct employment compensation. These disclosure forms have been filed with the Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation Editorial Office and are available for review, upon request, at COPDC@njhealth.org., (JCOPDF © 2019.)

Objective: The purpose of this study was to acquire normative data on central airway dimensions on chest CT scans in the pediatric population., Materials and Methods: Chest CT findings reported as normal by a radiologist were collected retrospectively at 10 international centers. An experienced and independent thoracic radiologist reevaluated all CT scans for image quality and for normal findings. Semiautomated image analysis was performed to measure dimensions of the trachea and right and left main bronchi at inspiration. Intrathoracic tracheal length was measured from carina to thorax inlet. Cross-sectional area and short and long axes were measured perpendicular to the longitudinal airway axis starting from the carina every centimeter upward for the trachea and every 0.5 cm downward for the main bronchi. The effects on airway diameters of age, sex, intrathoracic tracheal length, and distance from the carina were investigated by use of mixed-effects models analysis., Results: Among 1160 CT scans collected, 388 were evaluated as normal by the independent radiologist with sufficient image quality and adequate inspiratory volume level. Central airways were successfully semiautomatically analyzed in 294 of 388 CT studies. Age, sex, intrathoracic tracheal length, and distance from carina were all significant predictors in the models for tracheal and right and left main bronchial diameters (p < 0.001). The central airway dimensions increased with age up to 20 years, and dimensions were larger in male than in female adolescents., Conclusion: Normative data were determined for the central airways of children and adolescents. Central airway dimensions depended on distance from the carina and on intrathoracic tracheal length.

Airway obstruction and parenchymal destruction underlie phenotype and severity in chronic obstructive pulmonary disease (COPD). We aimed to predict, by clinical and pulmonary function data, the predominant type and severity of pathological changes quantitatively assessed by computed tomography (CT). Airway wall thickness (AWT-Pi10) and percentage of lung area with X-ray attenuation values <-950 HU (%LAA-950) were measured in 100 (learning set) out of 473 COPD outpatients undergoing clinical and functional evaluation. Original CT measurements were translated by principal component analysis onto a plane with the novel coordinates CT1 and CT2, depending on the difference (prevalent mechanism of airflow limitation) and on the sum (severity) of AWT-Pi10 and %LAA-950, respectively. CT1 and CT2, estimated in the learning set by cross-validated models of clinical and functional variables, were used to classify 373 patients in the testing set. A model based on diffusing capacity of the lung for carbon monoxide, total lung capacity and purulent sputum predicted CT1 (r = 0.64; p<0.01). A model based on forced expiratory volume in 1 s/vital capacity, functional residual capacity and purulent sputum predicted CT2 (r = 0.77; p<0.01). Classification of patients in the testing set obtained by model-predicted CT1 and CT2 reflected, according to correlations with clinical and functional variables, both COPD phenotype and severity. Multivariate models based on pulmonary function variables and sputum purulence classify patients according to overall severity and predominant phenotype of COPD as assessed quantitatively by CT.