Disseminated Echovirus 11 infection in a newborn in the Province of Bolzano, Italy.

PURPOSE: Recently, cases of serious illness in newborns infected with Echovirus 11 have been reported in Europe, including Italy. Here, we report the case of a newborn diagnosed with disseminated Echovirus 11 infection, which occurred in October 2023 in the Province of Bolzano, Italy. METHODS: A molecular screening, by Real-Time RT-PCR, was employed to analyse the cerebrospinal fluid, blood and stool samples, and nasal swabs. The entire viral genome was sequenced using both Illumina and Nanopore technologies. RESULTS: The patient was admitted to hospital due to fever. Molecular testing revealed the presence of enterovirus RNA. Typing confirmed the presence of Echovirus 11. The patient was initially treated with antibiotic therapy and, following the diagnosis of enterovirus infection, also with human immunoglobulins. Over the following days, the patient remained afebrile, with decreasing inflammation indices and in excellent general condition. Genomic and phylogenetic characterization suggested that the strain was similar to strains from severe cases reported in Europe. CONCLUSIONS: Despite the low overall risk for the neonatal population in Europe, recent cases of Echovirus 11 have highlighted the importance of surveillance and complete genome sequencing is fundamental to understanding the phylogenetic relationships of Echovirus 11 variants.

Effects of fingolimod on focal and diffuse damage in patients with relapsing-remitting multiple sclerosis - The "EVOLUTION" study.

BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), MRI markers can measure the potential neuroprotective effects of fingolimod beyond its anti-inflammatory activity. In this study we aimed to comprehensively explore, in the real-word setting, whether fingolimod not only reduces clinical/MRI inflammatory activity, but also influences the progression of irreversible focal and whole brain damage in relapsing-remitting [RR] MS patients. METHODS: The "EVOLUTION" study, a 24-month observational, prospective, single-arm, multicenter study, enrolled 261 RRMS patients who started fingolimod at 32 Italian MS centers and underwent biannual neurological assessments and annual MRI evaluations. Study outcomes included the proportions of evaluable RRMS patients achieving at 24 months: (1) no new/enlarging T2-hyperintense white matter (WM) lesions and/or clinical relapses; (2) a modified classification of "No Evidence of Disease Activity 4" ("modified NEDA-4") defined as no new/enlarging T2-hyperintense WM lesions, clinical relapses, and 6-month confirmed disability progression, and a yearly percentage lateral ventricular volume change on T2-FLAIR images < 2%; (3) less than 40% of active lesions at baseline and month 12 evolving to permanent black holes (PBHs). RESULTS: At month 24, 76/160 (47.5%; 95% confidence interval [CI] = 39.8%;55.2%) RRMS patients had no clinical/MRI activity. Thirty-nine of 170 RRMS patients (22.9%; 95% CI = 16.6%;29.3%) achieved "modified NEDA-4" status. Forty-four of 72 RRMS patients (61.1%; 95% CI = 49.8%;72.4%) had less than 40% of active WM lesions evolving to PBHs. The study confirmed the established safety and tolerability profile of fingolimod. DISCUSSION: By comparing our results with those from the literature, the EVOLUTION study seems to indicate a neuroprotective effect of fingolimod, limiting inflammatory activity, brain atrophy and PBH development.

Epidemiological impact of human adenovirus as causative agent of respiratory infections: An Italian multicentre retrospective study, 2022-2023.

Human adenoviruses are the causative agents of 5-7% of viral respiratory infections, mainly caused by species B and C. They can infect all age groups, but children are usually at high risk of infections. Adenovirus epidemiology is well documented in East-Asian countries but little is known about adenovirus circulation in Europe in recent years. This multicentre retrospective study aimed to investigate the circulation and molecular epidemiology of hAdVs. This surveillance collected a total of 54463 respiratory specimens between January 1, 2022 and June 20, 2023 were tested for the presence of respiratory viruses. Our results showed that adenovirus was detected in 6.6 % of all cases of acute respiratory infection included in the study and the median age of positive patients was 3 years, with male children in 1-2 years age group being the most affected. 43.5 % of adenovirus cases were co-infected with at least one other respiratory virus, and rhinovirus was co-detected in 54 % of cases. Genotyping of adenovirus allowed the identification of 6 different genotypes circulating in Italy, among which type B3 was the most frequently detected.

Brain and cervical spinal cord MRI correlates of sensorimotor impairment in patients with multiple sclerosis.

BACKGROUND: Cervical spinal cord (cSC) lesions and atrophy contribute to disability in multiple sclerosis (MS), but associations with specific sensorimotor dysfunction require further exploration. OBJECTIVE: To investigate the associations of brain and cSC magnetic resonance imaging (MRI) measures with sensorimotor impairment in MS. METHODS: One hundred fifty-one MS patients and 69 healthy controls underwent 3T MRI and clinical assessments including Expanded Disability Status Scale (EDSS), 9-hole peg test (9-HPT), finger tapping test (FTT), timed 25-foot walk test (T25FWT), and vibration detection threshold (VDT). Random forest ranked brain (T2-hyperintense lesion volume (T2-LV) and normalized deep gray matter (GM), cortical and white matter (WM) volumes) and cSC (T2-LV and total, GM, and WM cross-sectional areas (CSAs) at C2/C3 level) MRI measures relevance in explaining EDSS milestones (EDSS ⩾3.0, ⩾4.0, and ⩾6.0), VDT, pyramidal and sensory functional systems (P-FS and S-FS ⩾2), and motor tests impairment. RESULTS: Various combinations of brain and cSC MRI measures explained EDSS milestones (area under the curve (AUC) =0.879-0.900), VDT (R2 = 0.194), and impaired P-FS (AUC = 0.820), S-FS (AUC = 0.795), 9-HPT (AUC = 0.793), FTT (AUC = 0.740), and T25FWT (AUC = 0.825). cSC GM CSA was the most informative feature for all outcomes, except 9-HPT. CONCLUSION: cSC MRI measures, especially GM CSA, explain EDSS and sensorimotor dysfunction better than brain measures in MS.

Cerebrospinal Fluid-In Gradient of Cortical and Deep Gray Matter Damage in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: A CSF-in gradient in cortical and thalamic gray matter (GM) damage has been found in multiple sclerosis (MS). We concomitantly explored the patterns of cortical, thalamic, and caudate microstructural abnormalities at progressive distances from CSF using a multiparametric MRI approach. METHODS: For this cross-sectional study, from 3T 3D T1-weighted scans, we sampled cortical layers at 25%-50%-75% depths from pial surface and thalamic and caudate bands at 2-3-4 voxels from the ventricular-GM interface. Using linear mixed models, we tested between-group comparisons of magnetization transfer ratio (MTR) and R2* layer-specific z-scores, CSF-in across-layer z-score changes, and their correlations with clinical (disease duration and disability) and structural (focal lesions, brain, and choroid plexus volume) MRI measures. RESULTS: We enrolled 52 patients with MS (33 relapsing-remitting [RRMS], 19 progressive [PMS], mean age: 46.4 years, median disease duration: 15.1 years, median: EDSS 2.0) and 70 controls (mean age 41.5 ± 12.8). Compared with controls, RRMS showed lower MTR values in the outer and middle cortical layers (false-discovery rate [FDR]-p ≤ 0.025) and lower R2* values in all 3 cortical layers (FDR-p ≤ 0.016). PMS had lower MTR values in the outer and middle cortical (FDR-p ≤ 0.016) and thalamic (FDR-p ≤ 0.048) layers, and in the outer caudate layer (FDR-p = 0.024). They showed lower R2* values in the outer cortical layer (FDR-p = 0.003) and in the outer thalamic layer (FDR-p = 0.046) and higher R2* values in all 3 caudate layers (FDR-p ≤ 0.031). Both RRMS and PMS had a gradient of damage, with lower values closer to the CSF, for cortical (FDR-p ≤ 0.002) and thalamic (FDR-p ≤ 0.042) MTR. PMS showed a gradient of damage for cortical R2* (FDR-p = 0.005), thalamic R2* (FDR-p = 0.004), and caudate MTR (FDR-p ≤ 0.013). Lower MTR and R2* of outer cortical, thalamic, and caudate layers and steeper gradient of damage toward the CSF were significantly associated with older age, higher T2-hyperintense white matter lesion volume, higher thalamic lesion volume, and lower brain volume (ß ≥ 0.08, all FDR-p ≤ 0.040). Lower MTR of outer caudate layer was associated with more severe disability (ß = -0.26, FDR-p = 0.040). No correlations with choroid plexus volume were found. DISCUSSION: CSF-in damage gradients are heterogeneous among different GM regions and through MS course, possibly reflecting different dynamics of demyelination and iron loss/accumulation.

Structural and functional imaging features of cognitive phenotypes in pediatric multiple sclerosis.

OBJECTIVE: The present study aimed to identify the clinical and MRI features of the distinct cognitive phenotypes in pediatric multiple sclerosis (pedMS). METHODS: PedMS patients (n = 73) and healthy controls (n = 30) underwent clinical examination and 3.0T MRI. All patients completed neuropsychological testing, and cognitive phenotypes were identified by performing K-means clustering on cognitive scores. MRI metrics included brain T2-hyperintese lesion volume and normalized brain volumes. Within seven cognitively relevant cortical networks, structural disconnectivity (i.e., the mean percentage of streamlines connecting each pair of cortical regions passing through a lesion) and resting-state (RS) functional connectivity (FC) were estimated. RESULTS: Three cognitive phenotypes emerged: Preserved cognition (PC; n = 27, 37%), mild verbal learning and memory/semantic fluency involvement (MVS; n = 28, 38%), and multidomain involvement (MI; n = 18, 25%). Age, sex, and disease duration did not differ among groups. Compared with healthy subjects, PC patients had decreased RS FC within the default mode network (p = 0.045); MVS patients exhibited lower cortical volume and reduced RS FC within the frontoparietal network (all p = 0.045); and MI patients showed decreased volumes in all brain compartments except the hippocampus, and reduced RS FC within the frontoparietal network (all p ≤ 0.045). Compared to PC, MI patients had more severe disability and higher structural disconnectivity within four cortical networks (all p ≤ 0.045). Compared to PC and MVS, MI patients had lower intelligence quotient (all p ≤ 0.005). INTERPRETATION: We identified three cognitive phenotypes in pedMS that demonstrate the existence of a spectrum of impairment. Such phenotypes showed distinct clinical and MRI characteristics that contributed to explain their cognitive profiles.

Regional hippocampal atrophy reflects memory impairment in patients with early relapsing remitting multiple sclerosis.

BACKGROUND: Research work has shown that hippocampal subfields are atrophic to varying extents in multiple sclerosis (MS) patients. However, studies examining the functional implications of subfield-specific hippocampal damage in early MS are limited. We aim to gain insights into the relationship between hippocampal atrophy and memory function by investigating the correlation between global and regional hippocampal atrophy and memory performance in early MS patients. METHODS: From the Italian Neuroimaging Network Initiative (INNI) dataset, we selected 3D-T1-weighted brain MRIs of 219 early relapsing remitting (RR)MS and 246 healthy controls (HC) to identify hippocampal atrophic areas. At the time of MRI, patients underwent Selective-Reminding-Test (SRT) and Spatial-Recall-Test (SPART) and were classified as mildly (MMI-MS: n.110) or severely (SMI-MS: n:109) memory impaired, according to recently proposed cognitive phenotypes. RESULTS: Early RRMS showed lower hippocampal volumes compared to HC (p < 0.001), while these did not differ between MMI-MS and SMI-MS. In MMI-MS, lower hippocampal volumes correlated with worse memory tests (r = 0.23-0.37, p ≤ 0.01). Atrophic voxels were diffuse in the hippocampus but more prevalent in cornu ammonis (CA, 79%) than in tail (21%). In MMI-MS, decreased subfield volumes correlated with decreases in memory, particularly in the right CA1 (SRT-recall: r = 0.38; SPART: r = 0.34, p < 0.01). No correlations were found in the SMI-MS group. CONCLUSION: Hippocampal atrophy spreads from CA to tail from early disease stages. Subfield hippocampal atrophy is associated with memory impairment in MMI-MS, while this correlation is lost in SMI-MS. This plays in favor of a limited capacity for an adaptive functional reorganization of the hippocampi in MS patients.

Structural and functional correlates of disability, motor and cognitive performances in multiple sclerosis: Focus on the globus pallidus.

OBJECTIVES: To explore structural and functional alterations of external (GPe) and internal (GPi) globus pallidus in people with multiple sclerosis (pwMS) compared to healthy controls (HC) and analyze their relationship with measures of clinical disability, motor and cognitive impairment. METHODS: Sixty pwMS and 30 HC comparable for age and sex underwent 3.0T MRI, including conventional, diffusion tensor MRI and resting state (RS) functional MRI. Expanded Disability Status Scale (EDSS) scores were rated and timed 25-foot walk (T25FW) test, nine-hole peg test (9HPT), and paced auditory serial addition test (PASAT) were administered. Two operators segmented the GP into GPe and GPi. Volumes, T1/T2 ratio, diffusivity indices and seed-based RS functional connectivity (FC) of the GP and its components were assessed. RESULTS: PwMS had no atrophy or altered diffusivity measures of the GP. Compared to HC, pwMS had higher T1/T2 ratio in both GP regions, which correlated with EDSS score (r = 0.26-0.39, p = 0.01-0.05). RS FC analysis highlighted component-specific functional alterations in pwMS: the GPe had decreased RS FC with fronto-parietal cortices, whereas the GPi had decreased intra-GP RS FC and increased RS FC with the thalamus. Worse EDSS, 9HPT, T25FW and PASAT scores were associated with GP RS FC modifications (r=-0.51‒0.51, p < 0.001). CONCLUSIONS: Structural GP involvement in MS was homogeneous across its portions. Increased T1/T2 ratio values, possibly representing iron accumulation, were related to more severe disability. RS FC alterations of the GPe and GPi were consistent with their roles within the basal ganglia network and correlated with worse functional status, suggesting less efficient communication between structures.

Thalamic nuclei volume partially mediates the effects of aerobic capacity on fatigue in people with multiple sclerosis.

BACKGROUND: Fatigue is frequent in people with multiple sclerosis (pwMS) impacting physical and cognitive functions. Lower aerobic capacity and regional thalamic volume may be involved in the pathophysiology of fatigue in pwMS. OBJECTIVES: To identify associations between thalamic nuclei volumes, aerobic capacity and fatigue and to investigate whether the influence of aerobic capacity on fatigue in pwMS is mediated by thalamic integrity. METHODS: Eighty-three pwMS underwent a clinical evaluation with assessment of fatigue (Modified Fatigue Impact Scale [MFIS]), including physical (pMFIS) and cognitive (cMFIS) components, and peak of oxygen uptake (VO2peak). PwMS and 63 sex- and age-matched healthy controls (HC) underwent a 3 T brain MRI to quantify volume of the whole thalamus and its nuclei. RESULTS: Compared to HC, pwMS showed higher global MFIS, pMFIS and cMFIS scores, and lower VO2peak and thalamic volumes (p < 0.001). In pwMS, higher VO2peak was significantly associated with lower MFIS and pMFIS scores (r value = - 0.326 and - 0.356; pFDR ≤ 0.046) and higher laterodorsal thalamic nucleus (Dor) cluster volume (r value = 0.300; pFDR = 0.047). Moreover, lower Dor thalamic cluster volume was significantly associated with higher MFIS, pMFIS and cMFIS scores (r value range = - 0.305; - 0.293; pFDR ≤ 0.049). The volume of Dor thalamic cluster partially mediated the positive effects of VO2peak on both MFIS and cMFIS, with relative indirect effects of 21% and 32% respectively. No mediation was found for pMFIS. CONCLUSIONS: Higher VO2peak is associated with lower fatigue in pwMS, likely acting on Dor thalamic cluster volume integrity. Such an effect might be different according to the type of fatigue (cognitive or physical).

Cognitive Impairment Is Related to Glymphatic System Dysfunction in Pediatric Multiple Sclerosis.

OBJECTIVE: The aim of this study was to investigate whether, compared to pediatric healthy controls (HCs), the glymphatic system is impaired in pediatric multiple sclerosis (MS) patients according to their cognitive status, and to assess its association with clinical disability and MRI measures of brain structural damage. METHODS: Sixty-five pediatric MS patients (females = 62%; median age = 15.5 [interquartile range, IQR = 14.5;17.0] years) and 23 age- and sex-matched HCs (females = 44%; median age = 14.1 [IQR = 11.8;16.2] years) underwent neurological, neuropsychological and 3.0 Tesla MRI assessment, including conventional and diffusion tensor imaging (DTI). We calculated the diffusion along the perivascular space (DTI-ALPS) index, a proxy of glymphatic function. Cognitive impairment (Co-I) was defined as impairment in at least 2 cognitive domains. RESULTS: No significant differences in DTI-ALPS index were found between HCs and cognitively preserved (Co-P) pediatric MS patients (estimated mean difference [EMD] = -0.002 [95% confidence interval = -0.069; 0.065], FDR-p = 0.956). Compared to HCs and Co-P patients, Co-I pediatric MS patients (n = 20) showed significantly lower DTI-ALPS index (EMD = -0.136 [95% confidence interval = -0.214; -0.058], FDR-p ≤ 0.004). In HCs, no associations were observed between DTI-ALPS index and normalized brain, cortical and thalamic volumes, and normal-appearing white matter (NAWM) fractional anisotropy (FA) and mean diffusivity (MD) (FDR-p ≥ 0.348). In pediatric MS patients, higher brain WM lesion volume (LV), higher NAWM MD, lower normalized thalamic volume, and lower NAWM FA were associated with lower DTI-ALPS index (FDR-p ≤ 0.016). Random Forest selected lower DTI-ALPS index (relative importance [RI] = 100%), higher brain WM LV (RI = 59.5%) NAWM MD (RI = 57.1%) and intelligence quotient (RI = 51.3%) as informative predictors of cognitive impairment (out-of-bag area under the curve = 0.762). INTERPRETATION: Glymphatic system dysfunction occurs in pediatric MS, is associated with brain focal lesions, irreversible tissue loss accumulation and cognitive impairment. ANN NEUROL 2024;95:1080-1092.

Human Campylobacter spp. infections in Italy.

PURPOSE: Campylobacter is a frequent cause of enteric infections with common antimicrobial resistance issues. The most recent reports of campylobacteriosis in Italy include data from 2013 to 2016. We aimed to provide national epidemiological and microbiological data on human Campylobacter infections in Italy during the period 2017-2021. METHODS: Data was collected from 19 Hospitals in 13 Italian Regions. Bacterial identification was performed by mass spectrometry. Antibiograms were determined with Etest or Kirby-Bauer (EUCAST criteria). RESULTS: In total, 5419 isolations of Campylobacter spp. were performed. The most common species were C. jejuni (n = 4535, 83.7%), followed by C. coli (n = 732, 13.5%) and C. fetus (n = 34, 0.6%). The mean age of patients was 34.61 years and 57.1% were males. Outpatients accounted for 54% of the cases detected. Campylobacter were isolated from faeces in 97.3% of cases and in 2.7% from blood. C. fetus was mostly isolated from blood (88.2% of cases). We tested for antimicrobial susceptibility 4627 isolates (85.4%). Resistance to ciprofloxacin and tetracyclines was 75.5% and 54.8%, respectively; resistance to erythromycin was 4.8%; clarithromycin 2% and azithromycin 2%. 50% of C. jejuni and C. coli were resistant to ≥ 2 antibiotics. Over the study period, resistance to ciprofloxacin and tetracyclines significantly decreased (p < 0.005), while resistance to macrolides remained stable. CONCLUSION: Campylobacter resistance to fluoroquinolones and tetracyclines in Italy is decreasing but is still high, while macrolides retain good activity.

Chronic Active Lesions and Larger Choroid Plexus Explain Cognition and Fatigue in Multiple Sclerosis.

BACKGROUND AND OBJECTIVES: Chronic inflammation may contribute to cognitive dysfunction and fatigue in patients with multiple sclerosis (MS). Paramagnetic rim lesions (PRLs) and choroid plexus (CP) enlargement have been proposed as markers of chronic inflammation in MS being associated with a more severe disease course. However, their relation with cognitive impairment and fatigue has not been fully explored yet. Here, we investigated the contribution of PRL number and volume and CP enlargement to cognitive impairment and fatigue in patients with MS. METHODS: Brain 3T MRI, neurologic evaluation, and neuropsychological assessment, including the Brief Repeatable Battery of Neuropsychological Tests and Modified Fatigue Impact Scale, were obtained from 129 patients with MS and 73 age-matched and sex-matched healthy controls (HC). PRLs were identified on phase images of susceptibility-weighted imaging, whereas CP volume was quantified using a fully automatic method on brain three-dimensional T1-weighted and fluid-attenuated inversion recovery MRI sequences. Predictors of cognitive impairment and fatigue were identified using random forest. RESULTS: Thirty-six (27.9%) patients with MS were cognitively impaired, and 31/113 (27.4%) patients had fatigue. Fifty-nine (45.7%) patients with MS had ≥1 PRLs (median = 0, interquartile range = 0;2). Compared with HC, patients with MS showed significantly higher T2-hyperintense white matter lesion (WM) volume; lower normalized brain, thalamic, hippocampal, caudate, cortical, and WM volumes; and higher normalized CP volume (p from <0.001 to 0.040). The predictors of cognitive impairment (relative importance) (out-of-bag area under the curve [OOB-AUC] = 0.707) were normalized brain volume (100%), normalized caudate volume (89.1%), normalized CP volume (80.3%), normalized cortical volume (70.3%), number (67.3%) and volume (66.7%) of PRLs, and T2-hyperintense WM lesion volume (64.0%). Normalized CP volume was the only predictor of the presence of fatigue (OOB-AUC = 0.563). DISCUSSION: Chronic inflammation, with higher number and volume of PRLs and enlarged CP, may contribute to cognitive impairment in MS in addition to gray matter atrophy. The contribution of enlarged CP in explaining fatigue supports the relevance of immune-related processes in determining this manifestation independently of disease severity. PRLs and CP enlargement may contribute to the pathophysiology of cognitive impairment and fatigue in MS, and they may represent clinically relevant therapeutic targets to limit the impact of these clinical manifestations in MS.

Cognitive phenotypes in multiple sclerosis: mapping the spectrum of impairment.

BACKGROUND: Available criteria for cognitive phenotypes in multiple sclerosis (MS) do not consider the severity of impairment. OBJECTIVES: To identify cognitive phenotypes with varying degrees of impairment in MS patients and describe their demographic, clinical and MRI characteristics. METHODS: Two hundred and forty-three MS patients and 158 healthy controls underwent neuropsychological tests to assess memory, attention, and executive function. For each domain, mild impairment was defined as performing 1.5 standard deviations below the normative mean on two tests, while the threshold for significant impairment was 2 standard deviations. Patients were classified into cognitive phenotypes based on severity of the impairment (mild/significant) and number of domains affected (one/more). RESULTS: Five cognitive phenotypes emerged: Preserved cognition (PC; 56%), Mild Single-Domain Impairment (MSD; 15%), Mild Multi-Domain Impairment (MMD; 9%), Significant Single-Domain Impairment (SSD; 12%), Significant Multi-Domain Impairment (SMD; 8%). Compared with PC, MSD patients were older, had longer disease duration (DD) and higher T2-hyperintense lesion volume (LV; all p ≤ 0.02); MMD patients were older, had longer DD, higher disability, higher T2 LV and lower thalamic volume (all p ≤ 0.01); SSD patients had longer DD and lower gray matter cortical volume, thalamic, caudate, putamen and accumbens volumes (all p ≤ 0.04); and SMD patients were older, had longer DD, higher disability and more extensive structural damage in all brain regions explored (all p ≤ 0.03), except white matter and amygdala volumes. CONCLUSIONS: We identified five cognitive phenotypes with graded levels of impairment. These phenotypes were characterized by distinct demographic, clinical and MRI features, indicating potential variations in the neural substrates of dysfunction throughout disease stages.

A Fully Automatic Method to Segment Choroid Plexuses in Multiple Sclerosis Using Conventional MRI Sequences.

BACKGROUND: Choroid plexus (CP) volume has been recently proposed as a proxy for brain neuroinflammation in multiple sclerosis (MS). PURPOSE: To develop and validate a fast automatic method to segment CP using routinely acquired brain T1-weighted and FLAIR MRI. STUDY TYPE: Retrospective. POPULATION: Fifty-five MS patients (33 relapsing-remitting, 22 progressive; mean age = 46.8 ± 10.2 years; 31 women) and 60 healthy controls (HC; mean age = 36.1 ± 12.6 years, 33 women). FIELD STRENGTH/SEQUENCE: 3D T2-weighted FLAIR and 3D T1-weighted gradient echo sequences at 3.0 T. ASSESSMENT: Brain tissues were segmented on T1-weighted sequences and a Gaussian Mixture Model (GMM) was fitted to FLAIR image intensities obtained from the ventricle masks of the SIENAX. A second GMM was then applied on the thresholded and filtered ventricle mask. CP volumes were automatically determined and compared with those from manual segmentation by two raters (with 3 and 10 years' experience; reference standard). CP volumes from previously published automatic segmentation methods (freely available Freesurfer [FS] and FS-GMM) were also compared with reference standard. Expanded Disability Status Scale (EDSS) score was assessed within 3 days of MRI. Computational time was assessed for each automatic technique and manual segmentation. STATISTICAL TESTS: Comparisons of CP volumes with reference standard were evaluated with Bland Altman analysis. Dice similarity coefficients (DSC) were computed to assess automatic CP segmentations. Volume differences between MS and HC for each method were assessed with t-tests and correlations of CP volumes with EDSS were assessed with Pearson's correlation coefficients (R). A P value <0.05 was considered statistically significant. RESULTS: Compared to manual segmentation, the proposed method had the highest segmentation accuracy (mean DSC = 0.65 ± 0.06) compared to FS (mean DSC = 0.37 ± 0.08) and FS-GMM (0.58 ± 0.06). The percentage CP volume differences relative to manual segmentation were -0.1% ± 0.23, 4.6% ± 2.5, and -0.48% ± 2 for the proposed method, FS, and FS-GMM, respectively. The Pearson's correlations between automatically obtained CP volumes and the manually obtained volumes were 0.70, 0.54, and 0.56 for the proposed method, FS, and FS-GMM, respectively. A significant correlation between CP volume and EDSS was found for the proposed automatic pipeline (R = 0.2), for FS-GMM (R = 0.3) and for manual segmentation (R = 0.4). Computational time for the proposed method (32 ± 2 minutes) was similar to the manual segmentation (20 ± 5 minutes) but <25% of the FS (120 ± 15 minutes) and FS-GMM (125 ± 15 minutes) methods. DATA CONCLUSION: This study developed an accurate and easily implementable method for automatic CP segmentation in MS using T1-weighted and FLAIR MRI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 4.

Characterization of Verona Integron-Encoded Metallo-ß-Lactamase-Type Carbapenemase-Producing Escherichia coli Isolates Collected over a 16-Year Period in Bolzano (Northern Italy).

Multidrug-resistant Escherichia coli, particularly carbapenemase producers, are a major source of concern. This study aims to investigate the long-term epidemiology of Verona integron-encoded metallo-ß-lactamase (VIM)-producing E. coli in the health district of Bolzano, Northern Italy, by examining the phenotypic and genotypic characteristics of 26 isolates obtained during 2005-2020. Isolates were identified with matrix-assisted laser desorption/ionization time-of-flight, susceptibility testing was by Vitek 2, Sensititre, and Etest; carbapenemase activity was confirmed by Etest and Carbapenemase Inactivation Method (CIM) test; and the VIM-antigen was identified by the NG-Test CARBA 5. Genome sequencing was performed on an Illumina MiSeq platform. Carbapenem minimum inhibitory concentrations varied across methodologies, and overall category agreement between phenotypic methods was low. All 23 sequenced isolates contained blaVIM-1. Eleven (47.8%) isolates belonged to the clonal lineage ST131, with fimH30 being the most common subclone. In Bolzano ST131-fimH30 was present as early as 2005. While the ST131 clonal lineage predominated for the first 10 years, various clonal lineages were present, especially in subsequent years, indicating the concurrent circulation of multiple clonal lineages. Future efforts should focus on the implementation of surveillance methods, including genomic analysis, as well as the use of updated infection control strategies and antibiotic stewardship programs to prevent the spread of these carbapenem-resistant strains.

Quantification of Thalamic Atrophy in MS: From the Multicenter Italian Neuroimaging Network Initiative Data Set to Clinical Application.

BACKGROUND AND PURPOSE: Thalamic atrophy occurs from the earliest phases of MS; however, this measure is not included in clinical practice. Our purpose was to obtain a reliable segmentation of the thalamus in MS by comparing existing automatic methods cross-sectionally and longitudinally. MATERIALS AND METHODS: MR images of 141 patients with relapsing-remitting MS (mean age, 38 years; range, 19-58 years; 95 women) and 69 healthy controls (mean age, 36 years; range, 22-69 years; 47 women) were retrieved from the Italian Neuroimaging Network Initiative repository: T1WI, T2WI, and DWI at baseline and after 1 year (136 patients, 31 healthy controls). Three segmentation software programs (FSL-FIRST, FSL-MIST, FreeSurfer) were compared. At baseline, agreement among pipelines, correlations with age, disease duration, clinical score, and T2-hyperintense lesion volume were evaluated. Effect sizes in differentiating patients and controls were assessed cross-sectionally and longitudinally. Variability of longitudinal changes in controls and sample sizes were assessed. False discovery rate-adjusted P < .05 was considered significant. RESULTS: At baseline, FSL-FIRST and FSL-MIST showed the highest agreement in the results of thalamic volume (R = 0.87, P < .001), with the highest effect size for FSL-MIST (Cohen d = 1.11); correlations with demographic and clinical variables were comparable for all software. Longitudinally, FSL-MIST showed the lowest variability in estimating thalamic volume changes for healthy controls (SD = 1.07%), the highest effect size (Cohen d = 0.44), and the smallest sample size at 80% power level (15 subjects per group). CONCLUSIONS: Multimodal segmentation by FSL-MIST increased the robustness of the results with better capability to detect small variations in thalamic volumes.

Current Uses and Future Perspectives of Genomic Technologies in Clinical Microbiology.

Recent advancements in sequencing technology and data analytics have led to a transformative era in pathogen detection and typing. These developments not only expedite the process, but also render it more cost-effective. Genomic analyses of infectious diseases are swiftly becoming the standard for pathogen analysis and control. Additionally, national surveillance systems can derive substantial benefits from genomic data, as they offer profound insights into pathogen epidemiology and the emergence of antimicrobial-resistant strains. Antimicrobial resistance (AMR) is a pressing global public health issue. While clinical laboratories have traditionally relied on culture-based antimicrobial susceptibility testing, the integration of genomic data into AMR analysis holds immense promise. Genomic-based AMR data can furnish swift, consistent, and highly accurate predictions of resistance phenotypes for specific strains or populations, all while contributing invaluable insights for surveillance. Moreover, genome sequencing assumes a pivotal role in the investigation of hospital outbreaks. It aids in the identification of infection sources, unveils genetic connections among isolates, and informs strategies for infection control. The One Health initiative, with its focus on the intricate interconnectedness of humans, animals, and the environment, seeks to develop comprehensive approaches for disease surveillance, control, and prevention. When integrated with epidemiological data from surveillance systems, genomic data can forecast the expansion of bacterial populations and species transmissions. Consequently, this provides profound insights into the evolution and genetic relationships of AMR in pathogens, hosts, and the environment.

Sex-related differences in upper limb motor function in healthy subjects and multiple sclerosis patients: a multiparametric MRI study.

BACKGROUND: We investigated sex-related differences in upper limb motor performance tested with the 9-Hole Peg Test (9HPT) in healthy controls (HC) and multiple sclerosis (MS) patients and their MRI substrates. MATERIALS AND METHODS: We enrolled 94 HC and 133 MS patients, who underwent neurological examination, 9HPT and brain 3T MRI, with sequences for regional grey matter volume (GMV), white matter (WM) fractional anisotropy (FA) and resting state (RS) functional connectivity (FC) analysis. Associations between MRI variables and 9HPT performance were analyzed with general linear models. RESULTS: 9HPT performance was better in HC vs MS patients, and in female vs male HC. Regional GMV analysis showed: associations between better 9HPT performance and higher GMV in motor and cognitive cortical areas in HC, with stronger positive correlations in females vs males. In MS, worse 9HPT performance correlated with lower volume in motor and cognitive areas. Sex-related differences were minimal and mostly found in cerebellar areas. WM FA analysis disclosed neither associations with 9HPT performance in HC, nor sex-related differences in MS. RS FC analysis showed: in the sensorimotor network, stronger associations of RS FC with 9HPT performance in female vs male HC and no sex-related differences in MS; in the cerebellar network, no sex-related differences in HC but stronger negative correlation in left cerebellum in male vs female MS patients. CONCLUSIONS: Sex influences 9HPT performance in HC, mainly through differences in volume and RS FC of motor and cognitive areas. Sex-related effects on motor performance become secondary but still present in MS.

Influence of cardiorespiratory fitness and MRI measures of neuroinflammation on hippocampal volume in multiple sclerosis.

BACKGROUND: The hippocampus is a clinically relevant region where neurogenesis and neuroplasticity occur throughout the whole lifespan. Neuroinflammation and cardiorespiratory fitness (CRF) may influence hippocampal integrity by modulating the processes promoting neurogenesis and neuroprotection that contribute to the preservation of functions. This study aimed to investigate the effects of neuroinflammation and CRF on hippocampal volume in multiple sclerosis (MS) patients with relapsing-remitting (RR) and progressive (P) clinical phenotypes. The influence of neuroinflammation and CRF on brain, grey matter (GM) and thalamic volumes was also assessed to determine whether the effects were specific for the hippocampus. METHOD: Brain 3T structural MRI scans and maximum oxygen consumption (VO2max), a proxy of CRF, were acquired from 81 MS patients (27 RR and 54 P) and 45 age-matched and sex-matched healthy controls. T2-hyperintense white matter lesion volume (T2-LV) and choroid plexuses volume (CPV) were quantified as neuroinflammatory measures. Associations of demographic, clinical, neuroinflammatory and CRF measures with normalised brain, GM, hippocampal and thalamic volumes in relapsing-remitting MS (RRMS) and progressive MS patients were assessed using Shapley and best subset selection regression. RESULTS: For most volumetric measures, the largest portions of variance were explained by T2-LV (variable importance (VI)=9.4-39.4) and CPV (VI=4.5-26.2). VO2max explained the largest portion of variance of normalised hippocampal volume only in RRMS patients (VI=16.9) and was retained as relevant predictor (standardised ß=0.374, p=0.023) with T2-LV (standardised ß=-0.330, p=0.016). CONCLUSIONS: A higher CRF may play a specific neuroprotective role on MS patients' hippocampal integrity, but only in the RR phase of the disease.