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Objectives: To compare characteristics and outcomes of vesicoureteral reflux (VUR) detected solely on isotopic cystography (IC) ("occult" VUR) with voiding cystourethrography (VCUG)-detected VUR., Materials and Methods: Between 2015 and 2020, we retrospectively enrolled all male children first undergoing VCUG and, if negative, IC in the same session. Kidney injury (KI) was defined by abnormal estimated glomerular filtration rate and/or blood pressure and/or proteinuria., Results: We enrolled 421 males with a median age of 3 months and a follow-up of 5.3 years. None exhibited KI initially, but 10% of those with VUR developed KI during follow-up. Two hundred and twenty-two patients (52.7%) did not show VUR, 152 (36.1%) had VCUG-diagnosed VUR, and 47 (11.2%) had occult VUR. Therefore, 47/199 patients (23.6%) with VUR had occult VUR. Among these, 34/47 (72.3%) had dilated VUR, and 22/47 (46.8%) exhibited split renal function < 45% and/or scar (scintigraphic damage). Compared to patients with occult VUR, those with VCUG-diagnosed VUR showed a similar prevalence of febrile urinary tract infection (fUTI) before and after VUR diagnostics and KI at the last follow-up but a higher prevalence of dilated VUR, of scintigraphic damage, and underwent surgery more frequently. At multiple logistic regression analysis, patients with VCUG-diagnosed VUR presented an increased risk of fUTI either before or after VUR diagnosis and of KI, while patients with occult VUR presented an increased risk of fUTI before (and among patients with dilated VUR also after) VUR diagnosis and of KI., Conclusion: Occult VUR affects 23.6% of male children with VUR with a non-negligible risk of VUR-associated KI and fUTI. IC could select, among males with recurrent fUTIs and negative VCUG, those requiring surgery for a possible dilated occult VUR., Clinical Relevance Statement: Vesicoureteral reflux may be overlooked in 25% of boys during VCUG, yet they are at risk of fUTIs and KI. In case of recurrent infections post-negative cystourethrography, IC could detect occult reflux, guiding surgical intervention., (© 2024. The Author(s).)

Aim: To assess the prevalence and determinants of failure to thrive (FTT) among patients with vesico-ureteral reflux (VUR) and evaluating the effects of supplementation on growth in patients with urinary solute losses., Methods: We retrospectively enrolled 1277 patients with VUR (mean age at diagnosis = 6.5 months). Patients with FTT were screened for renal tubular function impairment (TFI). If fractional excretion of sodium (FENa) >2% or blood bicarbonate <20 mmol/L, supplementation was provided., Results: Among 1277 patients, 56 (4.4%) had FTT. Of these, 42 (75%) presented extrarenal causes of FTT, 3 (5.4%) had chronic kidney disease (CKD), 9 (16.1%) had TFI, and 2 (3.5%) had CKD and TFI. FTT occurred in 8/208 patients (3.8%) with and in 48/1069 patients (4.5%) without (p = 0.68) recurrent urinary tract infections (UTIs). At multiple logistic regression, birthweight <10th percentile, preterm birth, TFI, identified or suspected syndromes and other diseases were predictors of FTT. Eleven (19.6%) patients with FTT had TFI; five with increased FENa and/or acidosis received supplementation and showed catch-up growth. The remaining six patients exhibited spontaneous catch-up growth., Conclusion: FTT was found in <5% of children with VUR. It was not determined by recurrent UTIs and was mainly associated with extrarenal causes. Supplementation with sodium and bicarbonates could be useful in selected cases., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Background: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely., Objective: Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs)., Methods: Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes., Results: We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics., Conclusion: The patients in the PoB group had reduced SARS-CoV-2-specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways., Competing Interests: Disclosure statement Supported by the National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) (grants NIH/NHLBI T32HL116271 [to M.C.R., P.A.L., and N.S.]; the National Center for Advancing Translational Sciences of the NIH (UL1TR002378 [to N.S.]; P01AI125180 [to I.S. and F.E.L.]; U54CA260563 [to I.S. and F.E.L.]; R01AI121252 [to F.E.L.]; R01AI172254 [to F.E.L.]; U01AI141993 [to F.E.L.]; and NIH P51OD011132, 1U54CA260563, and the NIH/NIAID Centers of Excellence for Influenza Research and Response (under contract 75N93021C00017 to Emory University). This work does not necessarily represent the views of the US government or Department of Veterans Affairs. Disclosure of potential conflict of interest: N. S. Haddad is employed by MicroB-plex, Inc, but did not receive any payments for this article. C. Swenson receives compensation and consulting fees from Insmed, Inc, that are unrelated to this article. F. Holguin is a member of the adjudication committee of the ASPEN (A Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis) trial at Insmed, Inc. J. D. Roback received funding from an NIH grant in the past 36 months. I. Sanz receives royalties from BLI INC for plasma cell survival media; consulting fees from GSK, Pfizer, Kayverna, Johnson & Johnson, Celgene, Bristol-Myer Squibb, and Visterra; and honoraria for presentations from Yale and Harvard Universities. In addition, I. Sanz has a patent on plasma cell survival media. F. Eun-Hyung Lee receives or has received research grants from Genentech and the Gates Foundation; royalties from BLI INC for plasma cell survival media; consulting fees from Be Bio Pharma; honoraria for presentations at the University of Pennsylvania, the University of Cincinnati, and the Gerontological Advanced Practice Nurses Association; has patents on plasma cell survival media and media of elaborated newly synthesized antibodies (MENSA); and is the founder and owner of MicroB-plex, Inc. The rest of the authors declare that they have no relevant conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cerebellar syndromes are clinically and etiologically heterogeneous and can be classified as hereditary, neurodegenerative non-hereditary, or acquired. Few data are available on the frequency of each form in the clinical setting. Growing interest is emerging regarding the genetic forms caused by triplet repeat expansions. Alleles with repeat expansion lower than the pathological threshold, termed intermediate alleles (IAs), have been found to be associated with disease manifestation. In order to assess the relevance of IAs as a cause of cerebellar syndromes, we enrolled 66 unrelated Italian ataxic patients and described the distribution of the different etiology of their syndromes and the frequency of IAs. Each patient underwent complete clinical, hematological, and neurophysiological assessments, neuroimaging evaluations, and genetic tests for autosomal dominant cerebellar ataxia (SCA) and fragile X-associated tremor/ataxia syndrome (FXTAS). We identified the following diagnostic categories: 28% sporadic adult-onset ataxia, 18% cerebellar variant of multiple system atrophy, 9% acquired forms, 9% genetic forms with full-range expansion, and 12% cases with intermediate-range expansion. The IAs were six in the FMR1 gene, two in the gene responsible for SCA8, and one in the ATXN2 gene. The clinical phenotype of patients carrying the IAs resembles, in most of the cases, the one associated with full-range expansion. Our study provides an exhaustive description of the causes of cerebellar ataxia, estimating for the first time the frequency of IAs in SCAs- and FXTAS-associated genes. The high percentage of cases with IAs supports further screening among patients with cerebellar syndromes., (© 2023. The Author(s).)

Mixed primary progressive aphasia (mPPA) accounts for a substantial proportion of primary progressive aphasia (PPA) cases. However, the lack of a standardised definition of this condition has resulted in misclassification of PPA cases. In this study, we enrolled 55 patients diagnosed with PPA, comprising 12 semantic variant (svPPA), 23 logopenic variant (lvPPA), and 20 mPPA cases with linguistic characteristics consistent with both svPPA and lvPPA (s/lvPPA). All patients underwent language assessments, evaluation of Alzheimer's disease biomarkers (via cerebrospinal fluid analysis or Amyloid-PET), and 18 F-FDG-PET brain scans. An agglomerative hierarchical clustering (AHC) analysis based on linguistic characteristics revealed two distinct clusters within the s/lvPPA group: cluster k1 (n = 10) displayed an AD-like biomarker profile, with lower levels of Aβ 42 and Aβ 42 /Aβ 40 ratio, along with higher levels of t-tau and p-tau compared to cluster k2 (n = 10). Interestingly, k1 exhibited linguistic features that were similar to those of svPPA. Both clusters exhibited extensive temporoparietal hypometabolism. These findings support the hypothesis that a subgroup of s/lvPPA may represent a clinical manifestation of AD-related PPA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Primary progressive aphasia (PPA) diagnostic criteria underestimate the complex presentation of semantic (sv) and logopenic (lv) variants, in which symptoms partially overlap, and mixed clinical presentation (mixed-PPA) and heterogenous profile (lvPPA +) are frequent. Conceptualization of similarities and differences of these clinical conditions is still scarce., Methods: Lexical, semantic, phonological, and working memory errors from nine language tasks of sixty-seven PPA were analyzed using Profile Analysis based on Multidimensional Scaling, which allowed us to create a distributed representation of patients' linguistic performance in a shared space. Patients had been studied with [ 18 F] FDG-PET. Correlations were performed between metabolic and behavioral data., Results: Patients' profiles were distributed across a continuum. All PPA, but two, presented a lexical retrieval impairment, in terms of reduced production of verbs and nouns. svPPA patients occupied a fairly clumped space along the continuum, showing a preponderant semantic deficit, which correlated to fusiform gyrus hypometabolism, while only few presented working memory deficits. Adjacently, lvPPA + presented a semantic impairment combined with phonological deficits, which correlated with metabolism in the anterior fusiform gyrus and posterior middle temporal gyrus. Starting from the shared phonological deficit side, a large portion of the space was occupied by all lvPPA, showing a combination of phonological, lexical, and working memory deficits, with the latter correlating with posterior temporo-parietal hypometabolism. Mixed PPA did not show unique profile, distributing across the space., Discussion: Different clinical PPA entities exist but overlaps are frequent. Identifying shared and unique clinical markers is critical for research and clinical practice. Further research is needed to identify the role of genetic and pathological factors in such distribution, including also higher sample size of less represented groups., (© 2024. The Author(s).)

Little is known about empathy changes from the early stages of Alzheimer's Disease (AD) continuum. The aim of this study is to investigate empathy across AD spectrum from Subjective Cognitive Decline (SCD) to Mild Cognitive Impairment (MCI) and AD dementia (AD-d). Forty-five SCD, 83 MCI and 80 AD-d patients were included. Empathy was assessed by Interpersonal Reactivity Index (IRI) (Perspective Taking - PT, Fantasy - FT, Empathic Concern - EC, and Personal Distress - PD), rated by caregivers before (T0) and after (T1) cognitive symptoms' onset. IRI was also administered to SCD patients to have a self-reported empathy evaluation. Facial emotion recognition was assessed by Ekman-60 Faces Test. Twenty-two SCD, 54 MCI and 62 AD-d patients underwent CSF biomarkers analysis and were classified as carriers of AD pathology (AP+) when they were A+/T+ (regardless of N), or non-carriers (AP-) when they were A- (regardless of T and N), or A+/T-/N-, or A+/T-/N+ according to the A/T(N) system. Cerebral FDG-PET SPM analysis was used to explore neural correlates underlying empathy deficits. PD scores significantly increased from T0 to T1 in SCD, MCI and AD-d (p < .001), while PT scores decreased in MCI and in AD-d (p < .001). SCD AP+ showed a greater increase in PD scores over time (ΔPD T0 - T1) than SCD AP- (p < .001). SCD self-reported PT scores were lower than those of general Italian population (14.94 ± 3.94, 95% C.I. [13.68-16.20] vs 17.70 ± 4.36, 95% C.I. [17.30-18.10]). In AD continuum (SCD AP+, MCI AP+, AD-d), a positive correlation was detected between PT-T1 and brain metabolism in left posterior cingulate gyrus, precuneus and right frontal gyri; a negative correlation was found between ΔPT and brain metabolism in bilateral posterior cingulate gyri. PT may be subtly involved since the preclinical phase of AD. Changes over time of PD are influenced by the underlying Alzheimer's pathology and could potentially serve as an early AD neuropsychological marker., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction and Aim: NfL and GFAP are promising blood-based biomarkers for Alzheimer's disease. However, few studies have explored plasma GFAP in the prodromal and preclinical stages of AD. In our cross-sectional study, our aim is to investigate the role of these biomarkers in the earliest stages of AD., Materials and Methods: We enrolled 40 patients (11 SCD, 21 MCI, 8 AD dementia). All patients underwent neurological and neuropsychological examinations, analysis of CSF biomarkers (Aβ 42 , Aβ 42 /Aβ 40 , p-tau, t-tau), Apolipoprotein E (APOE) genotype analysis and measurement of plasma GFAP and NfL concentrations. Patients were categorized according to the ATN system as follows: normal AD biomarkers (NB), carriers of non-Alzheimer's pathology (non-AD), prodromal AD, or AD with dementia (AD-D)., Results: GFAP was lower in NB compared to prodromal AD (p = 0.003, d = 1.463) and AD-D (p = 0.002, d = 1.695). NfL was lower in NB patients than in AD-D (p = 0.011, d = 1.474). NfL demonstrated fair accuracy (AUC = 0.718) in differentiating between NB and prodromal AD, with a cut-off value of 11.65 pg/mL. GFAP showed excellent accuracy in differentiating NB from prodromal AD (AUC = 0.901) with a cut-off level of 198.13 pg/mL., Conclusions: GFAP exhibited excellent accuracy in distinguishing patients with normal CSF biomarkers from those with prodromal AD. Our results support the use of this peripheral biomarker for detecting AD in patients with subjective and objective cognitive decline., (© 2023. The Author(s).)

Background: In literature are reported different analytical methods (AM) to choose the proper fit model and to fit data of the time-activity curve (TAC). On the other hand, Machine Learning algorithms (ML) are increasingly used for both classification and regression tasks. The aim of this work was to investigate the possibility of employing ML both to classify the most appropriate fit model and to predict the area under the curve (τ)., Methods: Two different ML systems have been developed for classifying the fit model and to predict the biokinetic parameters. The two systems were trained and tested with synthetic TACs simulating a whole-body Fraction Injected Activity for patients affected by metastatic Differentiated Thyroid Carcinoma, administered with [ 131 I]I-NaI. Test performances, defined as classification accuracy (CA) and percentage difference between the actual and the estimated area under the curve (Δτ), were compared with those obtained using AM varying the number of points (N) of the TACs. A comparison between AM and ML were performed using data of 20 real patients., Results: As N varies, CA remains constant for ML (about 98%), while it improves for F-test (from 62 to 92%) and AICc (from 50 to 92%), as N increases. With AM, [Formula: see text] can reach down to - 67%, while using ML [Formula: see text] ranges within ± 25%. Using real TACs, there is a good agreement between τ obtained with ML system and AM., Conclusions: The employing of ML systems may be feasible, having both a better classification and a better estimation of biokinetic parameters., (© 2024. The Author(s).)

Background: Intensive treadmill training (TT) has been documented to improve gait parameters and functional independence in Parkinson's Disease (PD), but the optimal intervention protocol and the criteria for tailoring the intervention to patients' performances are lacking. TT may be integrated with augmented virtual reality (AVR), however, evidence of the effectiveness of this combined treatment is still limited. Moreover, prognostic biomarkers of rehabilitation, potentially useful to customize the treatment, are currently missing. The primary aim of this study is to compare the effects on gait performances of TT + AVR versus TT alone in II-III stage PD patients with gait disturbance. Secondary aims are to assess the effects on balance, gait parameters and other motor and non-motor symptoms, and patient's satisfaction and adherence to the treatment. As an exploratory aim, the study attempts to identify biomarkers of neuroplasticity detecting changes in Neurofilament Light Chain concentration T0-T1 and to identify prognostic biomarkers associated to blood-derived Extracellular Vesicles., Methods: Single-center, randomized controlled single-blind trial comparing TT + AVR vs. TT in II-III stage PD patients with gait disturbances. Assessment will be performed at baseline (T0), end of training (T1), 3 (T2) and 6 months (T3, phone interview) from T1. The primary outcome is difference in gait performance assessed with the Tinetti Performance-Oriented Mobility Assessment gait scale at T1. Secondary outcomes are differences in gait performance at T2, in balance and spatial-temporal gait parameters at T1 and T2, patients' satisfaction and adherence. Changes in falls, functional mobility, functional autonomy, cognition, mood, and quality of life will be also assessed at different timepoints. The G*Power software was used to estimate a sample size of 20 subjects per group (power 0.95, α  < 0.05), raised to 24 per group to compensate for potential drop-outs. Both interventions will be customized and progressive, based on the participant's performance, according to a predefined protocol., Conclusion: This study will provide data on the possible superiority of AVR-associated TT over conventional TT in improving gait and other motor and non-motor symptoms in persons with PD and gait disturbances. Results of the exploratory analysis could add information in the field of biomarker research in PD rehabilitation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lombardi, Baccini, Gualerzi, Pancani, Campagnini, Doronzio, Longo, Maselli, Cherubini, Piazzini, Ciapetti, Polito, Pinna, De Santis, Bedoni, Macchi, Ramat and Cecchi.)

A domain-specific perspective to cognitive functioning in stroke patients may predict their cognitive recovery over time and target stroke rehabilitation intervention. However, data about domain-specific cognitive impairment after stroke are still scarce. This study prospectively investigated the domain-specific pattern of cognitive impairments, using the classification proposed by the Montreal Cognitive Assessment (MoCA), in a cohort of 49 stroke patients at admission (T0), discharge (T1), and six-month follow-up (T2) from subacute intensive rehabilitation. The predictive value of T0 cognitive domains cognitive impairment at T1 and T2 was also investigated. Patients' cognitive functioning at T0, T1, and T2 was assessed through the MoCA domains for executive functioning, attention, language, visuospatial, orientation, and memory. Different evolutionary trends of cognitive domain impairments emerged across time-points. Patients' impairments in all domains decreased from T0 to T1. Attention and executive impairments decreased from T0 to T2 (42.9% and 26.5% to 10.2% and 18.4%, respectively). Conversely, altered visuospatial, language, and orientation increased between T1 and T2 (16.3%, 36.7%, and 40.8%, respectively). Additionally, patients' global cognitive functioning at T1 was predicted by the language and executive domains in a subacute phase ( p = 0.031 and p = 0.001, respectively), while in the long term, only attention ( p = 0.043) and executive ( p = 0.019) domains intervened. Overall, these results confirm the importance of a domain-specific approach to target cognitive recovery across time in stroke patients.

Background and Purpose: We aimed to evaluate the accuracy of plasma neurofilament light chain (NfL) in predicting Alzheimer's disease (AD) and the progression of cognitive decline in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI)., Methods: This longitudinal cohort study involved 140 patients (45 with SCD, 73 with MCI, and 22 with AD dementia [AD-D]) who underwent plasma NfL and AD biomarker assessments (cerebrospinal fluid, amyloid positron emission tomography [PET], and 18 F-fluorodeoxyglucose-PET) at baseline. The patients were rated according to the amyloid/tau/neurodegeneration (A/T/N) system and followed up for a mean time of 2.72 ± 0.95 years to detect progression from SCD to MCI and from MCI to AD. Forty-eight patients (19 SCD, 29 MCI) also underwent plasma NfL measurements 2 years after baseline., Results: At baseline, plasma NfL detected patients with biomarker profiles consistent with AD (A+/T+/N+ or A+/T+/N-) with high accuracy (area under the curve [AUC] 0.82). We identified cut-off values of 19.45 pg/mL for SCD and 20.45 pg/mL for MCI. During follow-up, nine SCD patients progressed to MCI (progressive SCD [p-SCD]), and 14 MCI patients developed AD dementia (progressive MCI [p-MCI]). The previously identified cut-off values provided good accuracy in identifying p-SCD (80% [95% confidence interval 65.69: 94.31]). The rate of NfL change was higher in p-MCI (3.52 ± 4.06 pg/mL) compared to non-progressive SCD (0.81 ± 1.25 pg/mL) and non-progressive MCI (-0.13 ± 3.24 pg/mL) patients. A rate of change lower than 1.64 pg/mL per year accurately excluded progression from MCI to AD (AUC 0.954)., Conclusion: Plasma NfL concentration and change over time may be a reliable, non-invasive tool to detect AD and the progression of cognitive decline at the earliest stages of the disease., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

The aims of the study were to assess empathy deficit and neuronal correlates in logopenic primary progressive aphasia (lv-PPA) and compare these data with those deriving from amnesic Alzheimer's disease (AD). Eighteen lv-PPA and thirty-eight amnesic AD patients were included. Empathy in both cognitive and affective domains was assessed by Informer-rated Interpersonal Reactivity Index (perspective taking, PT, and fantasy, FT, for cognitive empathy; empathic concern, EC, and personal distress, PD, for affective empathy) before (T0) and after (T1) cognitive symptoms' onset. Emotion recognition was explored through the Ekman 60 Faces Test. Cerebral FDG-PET was used to explore neural correlates underlying empathy deficits. From T0 to T1, PT scores decreased, and PD scores increased in both lv-PPA (PT z = -3.43, p = 0.001; PD z = -3.62, p < 0.001) and in amnesic AD (PT z = -4.57, p < 0.001; PD z = -5.20, p < 0.001). Delta PT (T0-T1) negatively correlated with metabolic disfunction of the right superior temporal gyrus, fusiform gyrus, and middle frontal gyrus (MFG) in amnesic AD and of the left inferior parietal lobule (IPL), insula, MFG, and bilateral superior frontal gyrus (SFG) in lv-PPA ( p < 0.005). Delta PD (T0-T1) positively correlated with metabolic disfunction of the right inferior frontal gyrus in amnesic AD ( p < 0.001) and of the left IPL, insula, and bilateral SFG in lv-PPA ( p < 0.005). Lv-PPA and amnesic AD share the same empathic changes, with a damage of cognitive empathy and a heightening of personal distress over time. The differences in metabolic disfunctions correlated with empathy deficits might be due to a different vulnerability of specific brain regions in the two AD clinical presentations., Competing Interests: The authors declare no conflict of interest.

Primary progressive aphasia (PPA) classification relies on profile characterization of quantitatively impaired/spared performance in language tasks. In this study, we coextracted 8 qualitative types of errors in 67 PPA patients submitted to a comprehensive language assessment. Canonical correlation analysis was applied to simultaneously correlate qualitative errors and brain metabolism, collected with FDG-PET. Results showed the contribution of semantic, syntactic and working memory errors associated with specific correlates of regional metabolic changes. Reduced metabolism in the left fusiform gyrus, anterior-middle and inferior-temporal gyri and middle-temporal pole correlated with an increase of semantic errors. Hypometabolism in the left inferior, middle, and superior frontal gyri, insula and right middle-occipital gyrus was related to syntactic errors. Higher metabolism in the bilateral pallidum, putamen, and left thalamus, as well as hypometabolism in the left angular and supramarginal gyri, inferior-parietal lobule, posterior-middle and inferior-temporal gyri and posterior cingulum predicted the increase of working memory errors. A relevant role of working memory subcomponents was associated with distinct neural systems. Patients' profiles are easily represented in a qualitative multidimensional space, in which mixed PPA overlapped with different phenotypes., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Our study aims to identify the optimal timing between a percutaneous cholecystostomy (PC) and cholecystectomy to reduce the number of poor surgical outcomes., Background: Biliary disease is a common surgical disease and laparoscopic cholecystectomy is the preferred strategy for the management of acute cholecystitis. However, in high-risk surgical patients, a PC tube may be placed instead. In the 2018 Tokyo Guidelines, the optimal timing of cholecystectomy following a PC has been identified as an important future research question., Methods: This is a retrospective study that focuses on identifying the ideal timing of cholecystectomy after PC tube placement to minimize complications. Poor surgical outcomes were measured as 90-day reoperations, 30-day readmissions, 30-day emergency department (ED) visits, length of stay (LOS), and discharge destination. Patients were selected from the New York SPARCS database from 2005 to September 30, 2015., Results: 1213 records that consisted of both PC and cholecystectomy were collected. No significant differences in 30-day readmissions, 90-day reoperations, and 30-day ED visits in relation to timing between PC and cholecystectomy were found. Additionally, the decision to replace or not replace dislodged PC tubes was not associated with 90-day reoperation, 30-day readmission, 30-day ED visit, LOS, or discharge destination. However, discharge destination and LOS were significantly different between early intervention of 3 days or less between PC and cholecystectomy and late intervention of more than 14 days with late intervention being associated with shorter LOS and more home discharges., Conclusion: Performing a cholecystectomy more than 14 days after a PC is associated with better surgical outcomes., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The early differential diagnosis among neurodegenerative parkinsonian disorders becomes essential to set up the correct clinical-therapeutic approach. The increased utilization of [ 18 F] fluoro-deoxy-glucose positron emission tomography (FDG PET) and the pressure for cost-effectiveness request a systematic evaluation and a validation of its utility in clinical practice. This retrospective study aims to consider the contribution, in terms of increasing accuracy and increasing diagnostic confidence, of voxel-based FDG PET analyses in the differential diagnosis of these disorders, including Parkinson's disease, multiple system atrophy, progressive supranuclear palsy, and cortico-basal syndrome., Method: Eighty-three subjects with a clinically confirmed diagnosis of degenerative parkinsonian disorders who underwent FDG brain PET/CT were selected. A voxel-based analysis was set up using statistical parametric mapping (SPM) on MATLAB to produce maps of brain hypometabolism and relative hypermetabolism. Four nuclear physicians (two expert and two not expert), blinded to the patients' symptoms, other physicians' evaluations, and final clinical diagnosis, independently evaluated all data by visual assessment and by adopting metabolic maps., Results: In not-expert evaluators, the support of both hypometabolism and hypermetabolism maps results in a significant increase in diagnostic accuracy as well as clinical confidence. In expert evaluators, the increase in accuracy and in diagnostic confidence is mainly supported by hypometabolism maps alone., Conclusions: In this study, we demonstrated the additional value of combining voxel-based analyses with qualitative assessment of brain PET images. Moreover, maps of relative hypermetabolism can also make their contribution in clinical practice, particularly for less experienced evaluators., (© 2022. The Author(s).)

We aimed to identify features associated with different disease trajectories in Alzheimer's disease (AD)-related primary progressive aphasia (PPA). We considered 23 patients diagnosed with AD-related PPA. All patients underwent neuropsychological evaluation, 18 F-Fluorodeoxyglucose-PET brain scan, CSF biomarkers measurement and APOE genotype analysis at baseline and underwent neurological follow-up for a mean time of 3 years. Patients who progressed to total loss of speech (TLoS + ) had greater impairment in writing and higher t-tau concentration as compared to TLoS - patients. Patients who progressed to loss of functional autonomy (LoFA + ) had greater impairment in single-word comprehension as compared to patients who maintained autonomy in self-care. Furthermore, 18 F-FDG-PET SPM analyses revealed different brain metabolic patterns between TLoS + and TLoS - and between LoFA + and LoFA - . In conclusion, linguistic profile, CSF t-tau and brain metabolic pattern might be useful tools to predict progression to total loss of speech and loss of functional autonomy in AD-related PPA patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: We hypothesized that children with congenital solitary functioning kidney (CSFK) present forms of congenital urinary tract anomalies (CUTA) with higher chance of spontaneous resolution compared with patients with two kidneys., Methods: We retrospectively selected 75 consecutive children with CUTA of the CSFK and 75 matched patients with unilateral CUTA but without CSFK (controls) with prenatal suspicion of unilateral CUTA and early evaluation. We compared the spontaneous CUTA resolution and the prevalence of kidney injury between groups at last follow-up. Patients and controls were clustered under the categories of "severe" and "non-severe" CUTA., Results: The mean age at first and last follow-up was 0.17 ± 0.07 and 8.5 ± 5.2 years. Compared with controls, patients with CSFK had lower prevalence of severe CUTA at first evaluation; lower prevalence of febrile urinary tract infections, need of surgical correction, and higher rate of spontaneous CUTA resolution during follow-up; and a similar prevalence of mild kidney injury at last follow-up. CSFK compared with controls presented higher cumulative proportion of spontaneous resolution from severe CUTA (100 vs 41.8%; p &lt; 0.001) and from the single CUTA sub-categories (severe vesicoureteral reflux, non-obstructive hydronephrosis, and megaureter)., Conclusions: CSFK patients had lower prevalence of severe forms and better outcomes of their CUTA compared with controls., Impact: One-third of patients with congenital solitary functioning kidney (CSFK) present congenital urinary tract anomalies (CUTA) and manifest poorer outcomes compared with CSFK without CUTA. CSFK patients had lower prevalence of severe forms and better outcomes of their CUTA in spite of similar prevalence of kidney injury compared with controls. This adds evidence about disturbed nephrogenesis in CSFK patients and emboldens conservative management of many of their non-obstructive CUTA., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Functional network-level alterations in the semantic variant of Primary Progressive Aphasia (sv-PPA) are relevant to understanding the clinical features and the neural spreading of the pathology. We assessed the effect of neurodegeneration on brain systems reorganization in early sv-PPA, using advanced brain metabolic connectivity approaches. Forty-four subjects with sv-PPA and forty-four age-matched healthy controls (HC) were included. We applied two multivariate approaches to [18F]FDG-PET data - i.e., sparse inverse covariance estimation and seed-based interregional correlation analysis - to assess the integrity of (i) the whole-brain metabolic connectivity and (ii) the connectivity of brain regions relevant for cognitive and behavioral functions. Whole-brain analysis revealed a global-scale connectivity reconfiguration in sv-PPA, with widespread changes in metabolic connections of frontal, temporal, and parietal regions. In comparison to HC, the seed-based analysis revealed a) functional isolation of the left anterior temporal lobe (ATL), b) decreases in temporo-occipital connections and contralateral homologous regions, c) connectivity increases to the dorsal parietal cortex from the spared posterior temporal cortex, d) a disruption of the large-scale limbic brain networks. In sv-PPA, the severe functional derangement of the left ATL may lead to an extensive connectivity reconfiguration, encompassing several brain regions, including those not yet affected by neurodegeneration. These findings support the hypothesis that in sv-PPA the focal vulnerability of the core region (i.e., ATL) can potentially drive the widespread cerebral connectivity changes, already present in the early phase., Competing Interests: Declaration of competing interest No competing financial interests exist., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression., Methods: We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10., Results: At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09-0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14-0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70-0.96) were associated with a significantly lower risk of AD progression., Conclusion: Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Empathy is the ability to understand (cognitive empathy) and to feel (affective empathy) what others feel. The aim of the study was to assess empathy deficit and neuronal correlates in Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) dementia. Twenty-four SCD, 41 MCI and 46 CE patients were included. Informer-rated Interpersonal Reactivity Index was used to explore cognitive (Perspective Taking-PT, Fantasy-FT) and affective (Empathic Concern-EC, Personal Distress-PD) empathy, before (T0) and after (T1) cognitive symptoms' onset. Emotion recognition ability was tested through Ekman-60 Faces Test. Cerebral FDG-PET SPM analysis was used to explore neural correlates underlying empathy deficits. FT-T1 scores were lower in AD compared to SCD (13.0 ± 8.0 vs 19.1 ± 4,7 p = 0.008), PD-T1 score were higher in AD compared to MCI and to SCD (27.00 ± 10.00 vs 25.3 ± 5.9 vs 20.5 ± 5.6, p = 0.001). A positive correlation was found between PT-T1 and metabolic disfunction of right middle gyrus (MFG) in MCI and AD. In AD group, a positive correlation between PT-T1 and insula and superior temporal gyrus (STG) metabolism was detected. A negative correlation was found between PD-T1 and superior parietal lobule metabolism in MCI, and between PD-T1 and STG metabolism in AD. Impairment of cognitive empathy starts at MCI stage. Increase of PD starts from preclinical phases and seems to be to be dissociated from cognitive decline. Loss of PT is related to a progressive involvement starting from right MFG in prodromal stage, extending to insula and STG in dementia. Heightened emotional contagion is probably related to derangement of mirror neurons systems in parietal regions in prodromal stages, and to impairment of temporal emotion inhibition system in advanced phases. Further studies are needed to clarify if alterations in emotional contagion might be a predictive feature of a cognitive decline driven by AD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

At type 1 diabetes mellitus (T1DM) onset, acute kidney injury (AKI) is very common. To diagnose AKI, the availability of a baseline serum creatinine (bSCr) is pivotal. However, in most hospitalized children the bSCr is unknown. We aimed to test whether the bSCr estimated on the basis of height (ebSCr) could be a reliable surrogate for AKI diagnosis compared with the measured bSCr (mbSCr). As the mbSCr, we considered the creatinine measured 14 days after T1DM onset while ebSCr (mg/dL) = (k × height [cm])/120 mL/min/1.73 m2, where k = 0.55 for children and adolescent girls and k = 0.7 for adolescent boys. AKI was defined as serum creatinine values >1.5 times the baseline creatinine. Kappa statistics and the percentage of agreement in AKI classification by ebSCr−AKI versus mbSCr−AKI definition methods were calculated. Bland−Altman plots were used to show the agreement between the creatinine ratio (highest/baseline creatinine; HC/BC) calculated with mbSCr and ebSCr. The number of 163 patients with T1DM onset were included. On the basis of mbSCr, 66/163 (40.5%) presented AKI while, on the basis of ebSCr, 50/163 (30.7%) accomplished AKI definition. ebSCr showed good correlation with mbSCr using both the Spearman test (rho = 0.67; p < 0.001) and regression analysis (r = 0.68; p < 0.001). Moreover, at the Bland−Altman plots, the bias of the highest/baseline creatinine ratio calculated on the basis of the mbSCr compared to ebSCr was minimal (bias = −0.08 mg/dL; 95% limits of agreement = −0.23/0.39). AKI determined using ebSCr showed 90% agreement with AKI determined using mbSCr (kappa = 0.66; p < 0.001). Finally, we compared the area under a receiver−operating characteristic curve (AUROC) of HC/BC ratio calculated on the basis of ebSCr with AUROC of the gold standard HC/BC ratio calculated on the basis of mbSCr. As expected, the gold standard had an AUROC = 1.00 with a 95% confidence interval (CI) between 0.98 and 1.00, p < 0.001. The HC/BC ratio calculated on the basis of ebSCr also had significant AUROC (AUROC = 0.94; 95% CI: 0.90−0.97; p < 0.001). The comparison of the two ROC curves showed a p < 0.001. In conclusion, when mbSCr is unknown in patients with T1DM onset, the ebSCr calculated on the basis of height could be an alternative to orientate clinicians toward AKI diagnosis.

Patients with idiopathic normal pressure hydrocephalus (iNPH) frequently show pathologic CSF Aβ 42 levels, comparable with Alzheimer's Disease (AD). Nevertheless, the clinical meaning of these findings has not been fully explained. We aimed to assess the role of AD CSF biomarkers (Aβ 42 , Aβ 42 /Aβ 40 , p-tau, t-tau) in iNPH. To this purpose, we enrolled 44 patients diagnosed with iNPH and 101 with AD. All the patients underwent CSF sampling. We compared CSF biomarker levels in iNPH and AD: Aβ 42 levels were not different between iNPH and AD, while Aβ 42 /Aβ 40 , p-tau, and t-tau were significantly different and showed excellent accuracy in distinguishing iNPH and AD. A multiple logistic regression analysis showed that Aβ 42 /Aβ 40 was the variable that most contributed to differentiating the two groups. Furthermore, iNPH patients with positive Aβ 42 /Aβ 40 had higher p-tau and t-tau than iNPH patients with negative Aβ 42 /Aβ 40 . Those iNPH patients who showed cognitive impairment had lower Aβ 42 /Aβ 40 and higher p-tau than patients without cognitive impairment. We concluded that positive CSF Aβ 42 with negative Aβ 42 /Aβ 40 , p-tau, and t-tau is a typical CSF profile of iNPH. On the contrary, positive Aβ 42 /Aβ 40 in iNPH patients, especially when associated with positive p-tau, may lead to suspicion of a coexistent AD pathology.