Publications by authors named "Paolo Gallo"

153 Publications

Alemtuzumab-induced autoimmune thyroid events in patients with relapsing-remitting multiple sclerosis: A real-life and monocentric experience at a tertiary-level centre.

Clin Endocrinol (Oxf) 2021 Nov 1. Epub 2021 Nov 1.

Department of Medicine (DIMED), Endocrinology Unit, Padua University, Padua, Italy.

Objective: Alemtuzumab-induced autoimmune thyroid events (AIATEs) are the most common adverse effects observed in relapsing-remitting multiple sclerosis (RRMS) patients. This study aims to explore the clinical and biochemical characteristics of such AIATEs, and to examine the risk factors for their occurrence, particularly for the worst clinical phenotype of fluctuating Graves' disease (GD).

Design, Patients, Measurements: We retrospectively analysed a real-life single-centre consecutive series of 57 RRMS patients treated with alemtuzumab whose clinical and biochemical parameters were collected before starting the treatment and then monthly during their follow-up.

Results: AIATEs developed in 39% of patients a mean 17 months ± 11 after the first cycle of alemtuzumab. The most common AIATEs were GD (64%), followed by Hashimoto's thyroiditis with hypothyroidism (23%), TSH-receptor-antibody (TRAb)-positive hypothyroidism (9%), and silent thyroiditis (4%). GD showed a fluctuating course in 57% of cases. Baseline positivity for anti-thyroperoxidase antibodies, and higher absolute titers of anti-thyroglobulin and anti-thyroperoxidase antibodies correlated significantly with the risk of developing AIATEs, but TRAb positivity did not. Higher TRAb titers at the time of GD being diagnosed correlated strongly with a greater risk of the fluctuating GD phenotype. On ROC curve analysis, we found that a cut-off of 7.3 IU/L could be used to predict the risk of developing a fluctuating GD, with a positive predictive value of 100%.

Conclusions: TRAb levels measured with commercial automatic methods at the time of a patient being diagnosed with alemtuzumab-induced GD emerged as a novel biomarker for predicting a fluctuating disease phenotype, with an influence on subsequent therapeutic decisions and patients' follow-up.
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http://dx.doi.org/10.1111/cen.14616DOI Listing
November 2021

Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis.

J Neurol 2021 Oct 9. Epub 2021 Oct 9.

University of Bari, Bari, Italy.

Early intervention with high-efficacy disease-modifying therapy (HE DMT) may be the best strategy to delay irreversible neurological damage and progression of multiple sclerosis (MS). In European healthcare systems, however, patient access to HE DMTs in MS is often restricted to later stages of the disease due to restrictions in reimbursement despite broader regulatory labels. Although not every patient should be treated with HE DMTs at the initial stages of the disease, early and unrestricted access to HE DMTs with a positive benefit-risk profile and a reasonable value proposition will provide the freedom of choice for an appropriate treatment based on a shared decision between expert physicians and patients. This will further optimize outcomes and facilitate efficient resource allocation and sustainability in healthcare systems and society.
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http://dx.doi.org/10.1007/s00415-021-10836-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501364PMC
October 2021

Combined evaluation of aminotransferases improves risk stratification for overall and cause-specific mortality in older patients.

Aging Clin Exp Res 2021 Sep 10. Epub 2021 Sep 10.

Clinical Medicine and Hepatology Unit, Campus Bio-Medico University, Rome, Italy.

Background: Recent studies identified low levels of alanine aminotransferase (ALT) as strong predictors of mortality in older people.

Aims: Here we verified if the combined evaluation of aminotransferases may improve risk stratification for adverse outcomes in older patients.

Methods: Data are from 761 participants aged more than 65 years from a prospective population-based database (InCHIANTI study), without known baseline chronic liver disease or malignancies. Associations between aminotransferase levels and the risk of all-cause, cardiovascular- and cancer-death were assessed by Cox-models with time-dependent covariates.

Results: The association of ALT and aspartate aminotransferase (AST) with mortality was non-linear, mirroring a J- and a U-shaped curve, respectively. Based on quintiles of transaminase activities and on their association with overall mortality, low, intermediate (reference group) and high levels were defined. Having at least one transaminase in the low range [aHR 1.76 (1.31-2.36), p < 0.001], mainly if both [(aHR 2.39 (1.81-3.15), p < 0.001], increased the risk of overall mortality, as well as having both enzymes in the high range [aHR 2.14 (1.46-3.15), p < 0.001]. While similar trends were confirmed with respect to cardiovascular mortality, subjects with the highest risk of cancer mortality were those with both enzymes in the high range [aHR 3.48 (1.43-8.44), p = 0.006]. Low levels of transaminases were associated with frailty, sarcopenia and disability, while high levels did not capture any known proxy of adverse outcome. Conclusions and discussion The prognostic information is maximized by the combination of the 2 liver enzymes. While both aminotransferases in low range are characteristically found in the most fragile phenotype, both enzymes in high range are more likely to identify new-onset vascular/infiltrative diseases with adverse outcome.
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http://dx.doi.org/10.1007/s40520-021-01979-9DOI Listing
September 2021

Usefulness of Adding Pre-procedural Glycemia to the Mehran Score to Enhance Its Ability to Predict Contrast-induced Kidney Injury in Patients Undergoing Percutaneous Coronary Intervention Development and Validation of a Predictive Model.

Am J Cardiol 2021 09 17;155:16-22. Epub 2021 Jul 17.

Unit of Cardiac Sciences, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.

The Mehran score is the most widely accepted tool for predicting contrast-induced acute kidney injury (CI-AKI), a major complication of percutaneous coronary intervention (PCI). Similarly, abnormal fasting pre-procedural glycemia (FPG) represents a modifiable risk factor for CI-AKI, but it is not included in current risk models for CI-AKI prediction. We sought to analyze whether adding FPG to the Mehran score improves its ability to predict CI-AKI following PCI. We analyzed 671 consecutive patients undergoing PCI (age 69 [63,75] years, 23% females), regardless of their diabetic status, to derive a revised Mehran score obtained by including FPG in the original Mehran score (Derivation Cohort). The new risk model (GlyMehr) was externally validated in 673 consecutive patients (Validation Cohort) (age 69 [62,76] years, 21% females). In the Derivation Cohort, both FPG and the original Mehran score predicted CI-AKI (AUC 0.703 and 0.673, respectively). The GlyMehr score showed a better predictive ability when compared with the Mehran score both in the Derivation Cohort (AUC 0.749, 95%CI 0.662 to 0.836; p = 0.0016) and the Validation Cohort (AUC 0.848, 95%CI, 0.792 to 0.903; p = 0.0008). In the overall population (n = 1344), the GlyMehr score confirmed its independent and incremental predictive ability regardless of diabetic status (p ≤0.0034) or unstable/stable coronary syndromes (p ≤0.0272). In conclusion, adding FPG to the Mehran score significantly enhances our ability to predict CI-AKI. The GlyMehr score may contribute to improve the clinical management of patients undergoing PCI by identifying those at high risk of CI-AKI and potentially detecting modifiable risk factors.
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http://dx.doi.org/10.1016/j.amjcard.2021.06.014DOI Listing
September 2021

Designing a Self-Perception Cognitive Questionnaire for Italian Multiple Sclerosis Patients (Sclerosi Multipla Autovalutazione Cognitiva, SMAC). A Preliminary Exploratory Pilot Study.

Front Neurol 2021 28;12:668933. Epub 2021 Jun 28.

Department of Neuroscience, Multiple Sclerosis Center, University of Padua, Padua, Italy.

Although cognition in multiple sclerosis (MS) is assessed by means of several neuropsychological tests, only a few tools exist to investigate patients' perspectives on cognitive functioning. To develop a new questionnaire aimed at exploring patients' self-perception with respect to cognition in Italian MS patients. A total of 120 relapsing-remitting MS (RRMS) patients and 120 matched healthy controls (HC) completed a 25-item questionnaire called the Sclerosi Multipla Autovalutazione Cognitiva (SMAC). The Symbol Digit Modalities Test (SDMT), the Delis-Kaplan Executive Function System Sorting Test (D-KEFS ST), the Beck Depression Inventory (BDI-II), and the Fatigue Scale (FSS) were also administered to the patients. Significantly higher SMAC scores were displayed by RRMS patients compared with HC (30.1 ± 16.9 vs. 23.4 ± 10.4, = 0.003). SMAC inversely correlated with SDMT ( = -0.31, < 0.001), D-KEFS ST FSC ( = -0.21, = 0.017), D-KEFS ST FSD ( = -0.22, = 0.015) and D-KEFS ST SR ( = -0.19, = 0.035) and positively correlated with FSS ( = 0.42, < 0.001) and BDI-II ( = 0.59, < 0.001). Cronbach's alpha coefficient for the questionnaire was 0.94. Preliminary findings suggest that SMAC is a promising patient-reported outcome to be included in MS neuropsychological evaluation and thus warrants being further tested and developed.
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http://dx.doi.org/10.3389/fneur.2021.668933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273489PMC
June 2021

Therapy of Pediatric-Onset Multiple Sclerosis: State of the Art, Challenges, and Opportunities.

Front Neurol 2021 17;12:676095. Epub 2021 May 17.

Multiple Sclerosis Centre of the Veneto Region (CeSMuV), University Hospital of Padua, Padua, Italy.

Treatment of pediatric-onset multiple sclerosis (POMS) has been tailored after observational studies and data obtained from clinical trials in adult-onset multiple sclerosis (AOMS) patients. There are an increasing number of new therapeutic agents for AOMS, and many will be formally studied for use also in POMS. However, there are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss the current state of the art of POMS therapy and will focus on the newer therapies (oral and infusion disease-modifying drugs) and on those still currently under investigation.
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http://dx.doi.org/10.3389/fneur.2021.676095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165183PMC
May 2021

Oligoclonal IgG bands in chronic inflammatory polyradiculoneuropathies.

J Neurol Neurosurg Psychiatry 2021 Sep 13;92(9):969-974. Epub 2021 Apr 13.

Department of Neurosciences (DNS), University of Padova, Padova, Italy

Background: Cerebrospinal fluid (CSF) albumincytologic dissociation represents a supportive diagnostic criterion of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP).Few studies have investigated possible systemic or intrathecal humoral immune response activation in CIDP.Aim of our study was to investigate whether the search of oligoclonal IgG bands (OCBs) might provide additional data helpful in CIDP diagnostic work-up.

Methods: Forty-eight consecutive patients with CIDP (34 men, mean age 59.4, range 16-83) were recruited. CSF analysis included nephelometric measurement of albumin and IgG concentrations, calculation of Q, QAlb and intrathecal IgG synthesis, and OCBs detection with isoelectric focusing. Data were compared with those from CSF and serum of 32 patients with Guillain-Barré syndrome (GBS), 18 patients with anti-myelin associated glycoprotein (MAG) antibody neuropathy, 4 patients with multifocal motor neuropathy and 32 patients with non-inflammatory neuropathies (NINPs).

Results: Patients with CIDP and anti-MAG antibody neuropathy had significantly higher CSF albumin concentrations and Q values than NINPs (p=0.0003 and p=0.0095, respectively). A total of 9 (19%) patients with CIDP presented identical serum and CSF OCBs ('mirror pattern') versus 3 patients (16.6%) with anti-MAG antibody neuropathy, 13 patients (40.6%) with GBS and 12.5% patients with NINPs. Only one patient with CIDP showed unique-to-CSF OCBs. First-line therapy was effective in 80.4% of patients with CIDP, irrespective of CSF findings.

Conclusions: Compared with NINP, CIDP, GBS and anti-MAG antibody neuropathies had a significantly increased CSF protein and blood-spinal nerve root barrier damage. Intrathecal humoral immune response is rare in our patients with CIDP. Systemic oligoclonal activation is more frequent, but not significantly different from what was detected in the control groups.
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http://dx.doi.org/10.1136/jnnp-2020-325868DOI Listing
September 2021

Identifying the Distinct Cognitive Phenotypes in Multiple Sclerosis.

JAMA Neurol 2021 Apr;78(4):414-425

Section Neurosciences, Dipartimento di Neuroscienze, Psicologia, Area del Farmaco e Salute del Bambino, University of Florence, Florence, Italy.

Importance: Cognitive impairment is a common and disabling feature of multiple sclerosis (MS), but a precise characterization of cognitive phenotypes in patients with MS is lacking.

Objectives: To identify cognitive phenotypes in a clinical cohort of patients with MS and to characterize their clinical and magnetic resonance imaging (MRI) features.

Design, Setting, And Participants: This multicenter cross-sectional study consecutively screened clinically stable patients with MS and healthy control individuals at 8 MS centers in Italy from January 1, 2010, to October 31, 2019. Patients with MS and healthy control individuals who were not using psychoactive drugs and had no history of other neurological or medical disorders, learning disability, severe head trauma, and alcohol or drug abuse were enrolled.

Main Outcomes And Measures: Participants underwent a neurological examination and a cognitive evaluation with the Rao Brief Repeatable Battery and Stroop Color and Word Test. A subgroup of participants also underwent a brain MRI examination. Latent profile analysis was used on cognitive test z scores to identify cognitive phenotypes. Linear regression and mixed-effects models were used to define clinical and MRI features of each phenotype.

Results: A total of 1212 patients with MS (mean [SD] age, 41.1 [11.1] years; 784 women [64.7%]) and 196 healthy control individuals (mean [SD] age, 40.4 [8.6] years; 130 women [66.3%]) were analyzed in this study. Five cognitive phenotypes were identified: preserved cognition (n = 235 patients [19.4%]), mild-verbal memory/semantic fluency (n = 362 patients [29.9%]), mild-multidomain (n = 236 patients [19.5%]), severe-executive/attention (n = 167 patients [13.8%]), and severe-multidomain (n = 212 patients [17.5%]) involvement. Patients with preserved cognition and mild-verbal memory/semantic fluency were younger (mean [SD] age, 36.5 [9.8] years and 38.2 [11.1] years) and had shorter disease duration (mean [SD] 8.0 [7.3] years and 8.3 [7.6] years) compared with patients with mild-multidomain (mean [SD] age, 42.6 [11.2] years; mean [SD] disease duration, 12.8 [9.6] years; P < .001), severe-executive/attention (mean [SD] age, 42.9 [11.7] years; mean [SD] disease duration, 12.2 [9.5] years; P < .001), and severe-multidomain (mean [SD] age, 44.0 [11.0] years; mean [SD] disease duration, 13.3 [10.2] years; P < .001) phenotypes. Severe cognitive phenotypes prevailed in patients with progressive MS. At MRI evaluation, compared with those with preserved cognition, patients with mild-verbal memory/semantic fluency exhibited decreased mean (SE) hippocampal volume (5.42 [0.68] mL vs 5.13 [0.68] mL; P = .04), patients with the mild-multidomain phenotype had decreased mean (SE) cortical gray matter volume (687.69 [35.40] mL vs 662.59 [35.48] mL; P = .02), patients with severe-executive/attention had higher mean (SE) T2-hyperintense lesion volume (51.33 [31.15] mL vs 99.69 [34.07] mL; P = .04), and patients with the severe-multidomain phenotype had extensive brain damage, with decreased volume in all the brain structures explored, except for nucleus pallidus, amygdala and caudate nucleus.

Conclusions And Relevance: This study found that by defining homogeneous and clinically meaningful phenotypes, the limitations of the traditional dichotomous classification in MS can be overcome. These phenotypes can represent a more meaningful measure of the cognitive status of patients with MS and can help define clinical disability, support clinicians in treatment choices, and tailor cognitive rehabilitation strategies.
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http://dx.doi.org/10.1001/jamaneurol.2020.4920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783596PMC
April 2021

Association of Multiple Sclerosis with PM 2.5 levels. Further evidence from the highly polluted area of Padua Province, Italy.

Mult Scler Relat Disord 2021 Feb 6;48:102677. Epub 2020 Dec 6.

Multiple Sclerosis Centre of the Veneto Region, Neurology Clinic, Department of Neurosciences (DNS), University of Padua, Via Giustinaini 2, 35128, Italy. Electronic address:

Background: Fifty years of epidemiological survey and intra-regional differences in prevalence suggest that environmental factors may be associated with increased multiple sclerosis (MS) risk in Northern Italy. Based on the findings of a previous study carried out in the highly polluted Padan Plain, we further explored the relationship between PM2.5 levels and MS prevalence by comparing bordering areas characterized by quite different environmental conditions, namely the Municipality of Padua and the special protected zone (SPZ) of the Euganean Hills Regional Park, located 15 km from the City.

Methods: Three territories were identified; 1) the SPZ, extending over an area of 15.096 hectares and having a total population of 23,980 inhabitants, 2) the urban area of Padua, with a total population of 210,440 inhabitants and repeatedly recognized by the European Invironmental Agency as one of the most polluted Cities of Europe, 3) the Intermediate Zone (IZ), i.e., the area in between the previous two, including part of the urban territories of eight villages adjacent to the SPZ. Demographic and socio-economical data were obtained from official government sources (www.istat.it and www.regione.veneto.it). All Italian MS patients residing in these three areas on December 31, 2018, were registered. PM2.5 concentrations (annual average 1998-2018, μg/m3) were measured by satellite. The correlation between PM2.5 concentrations and MS prevalence was analysed.

Results: MS prevalence was significantly higher in Padua City (265/100.000) compared to both the SPZ of the Euganean Hills Park (160/100,000; p < 0.0001) and the IZ (194.4/100,000). Prevalence strongly associated with the annual average concentration of PM2.5 (r = 0.89 p < 0.00001).

Conclusion: In the Province of Padua, one of the most polluted areas of Europe, MS prevalence is strongly associated with PM2.5 exposure. Our findings suggest that air pollutants may be one of the possible environmental risk factors for MS in the Veneto Region of Italy.
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http://dx.doi.org/10.1016/j.msard.2020.102677DOI Listing
February 2021

Steroid-refractory immune related hepatitis may hide viral re-activation.

Future Sci OA 2020 Aug 6;6(9):FSO614. Epub 2020 Aug 6.

Department of Medical Oncology, Campus Bio-Medico University, Via Alvaro del Portillo 200, Rome, Italy.

Cancer immunotherapy has become a stronghold in modern oncology. Immune checkpoint inhibitors, in particular anti-PD-1 and anti-PD-L1 antibodies, are approved for the treatment of several solid cancers. In the near future, an increasing number of patients will be eligible for immunotherapy. Therefore, the management of immune-related adverse events is a daily challenge in clinical practice, among which hepatic immune-related toxicity has been described as a rare adverse event. We report the case of a patient treated with nivolumab (an anti-PD-L1 antibody) for a stage IV resected melanoma who developed recurrence of steroid-refractory liver toxicity that was later discovered to be associated with acute exacerbation of chronic undiagnosed hepatitis B. The patient significantly benefited from antiviral treatment. We conclude that serological viral screening is strongly recommended before starting immune checkpoint inhibitor treatment.
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http://dx.doi.org/10.2144/fsoa-2020-0056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668132PMC
August 2020

REabsorbable vs. DUrable Polymer Drug-Eluting Stents in All-Comer PatiEnts: the REDUCE registry.

Coron Artery Dis 2021 Jun;32(4):281-287

Unit of Cardiovascular Science, Department of Medicine, Campus Bio-Medico University, Rome.

Background: While the superiority of reabsorbable-polymer drug-eluting stents (RP-DES) over bare-metal stents and first-generation durable-polymer (DP)-DES has been largely established, their advantage compared with new-generation DP-DES is still controversial. This study aimed was to compare clinical outcomes of all-comer patients undergoing percutaneous coronary intervention (PCI) with new generation DP-DES or RP-DES implantation.

Methods: We prospectively enrolled 679 consecutive patients treated with PCI with RP-DES or DP-DES. The primary endpoint was the 1-year incidence of major adverse clinical events (MACE), a composite of death, myocardial infarction (MI), and target vessel revascularization (TVR). Target lesion revascularization (TLR) and definite stent thrombosis were also recorded.

Results: A total of 439 (64.6%) received RP-DES and 240 (36.4%) received DP-DES. No significant difference in the incidence of MACE (5.9 vs. 4.9%; hazard ratio, 1.23; 95% confidence interval (CI), 0.61-2.49; P = 0.569), death (1.8 vs. 1.7%; hazard ratio, 1.09; 95% CI, 0.33-3.64; P = 0.882), MI (2.3 vs. 2.1%; hazard ratio, 1.05; 95% CI, 0.36-3.08; P = 0.927), TVR (2.3 vs. 1.3%; hazard ratio, 1.70; 95% CI, 0.47-6.20; P = 0.418), TLR (1.4 vs. 0.4%; hazard ratio, 3.06; 95% CI, 0.37-25.40; P = 0.301), and definite stent thrombosis (0.5 vs. 0.4%; hazard ratio, 1.09; 95% CI, 0.10-12.10; P = 0.942) was observed between RP-DES and DP-DES patients at 1-year follow-up. These results were confirmed in a propensity score-matched cohort (n = 134 per group).

Conclusion: In our registry including a real-world population of all-comer patients undergoing PCI, RP-DES, or durable polymer-DES showed similar efficacy and safety at a 1-year follow-up.
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http://dx.doi.org/10.1097/MCA.0000000000000993DOI Listing
June 2021

Natalizumab safety in paediatric-onset multiple sclerosis at the time of SARS-Cov-2 pandemic.

Mult Scler J Exp Transl Clin 2020 Oct-Dec;6(4):2055217320966346. Epub 2020 Oct 12.

The Multiple Sclerosis Centre of the Veneto Region of Italy, Department of Neurosciences, University Hospital- School of Medicine, Padua, Italy.

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http://dx.doi.org/10.1177/2055217320966346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556166PMC
October 2020

Early red nucleus atrophy in relapse-onset multiple sclerosis.

Hum Brain Mapp 2021 01 13;42(1):154-160. Epub 2020 Oct 13.

Multiple Sclerosis Centre of the Veneto Region (CeSMuV), University Hospital of Padua, Padua, Italy.

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS-related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty-seven relapse-onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18-56) years and mean disease duration of 1.1 ± 1.5 (0-5) years, and 36 age- and sex-matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T-MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 ± 13.95 mm vs. 99.37 ± 11.53 mm , p = .019) and left (109.71 ± 14.94 mm vs. 100.47 ± 15.78 mm , p = .020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = -.333, p = .004 and r = -.298, p = .010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN: r = -.147, p = .216; left RN: r = -.153, p = .196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = -.310, p = .008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN: r = -.164, p = .164; left RN: r = -.64, p = .588). Finally, left RN volume correlated with vermis VIIb (r = .297, p = .011) and right interposed nucleus (r = .249, p = .034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS.
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http://dx.doi.org/10.1002/hbm.25213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721227PMC
January 2021

Current Treatment Options for HCC: From Pharmacokinetics to Efficacy and Adverse Events in Liver Cirrhosis.

Curr Drug Metab 2020 ;21(11):866-884

Unit of Clinical Medicine and Hepatology, University Campus Bio-Medico, Rome, Italy.

Background: Hepatocellular carcinoma (HCC) is among the world's most common cancers. For over ten years, the only medical treatment for it has been the multikinase inhibitor Sorafenib. Currently, however, other first or second-line therapeutic options have also shown efficacy against HCC, such as multikinase inhibitors (Regorafenib, Lenvatinib, and Cabozantinib), a monoclonal antibody against the vascular endothelial growth factor receptor 2 (Ramucirumab), and immune-checkpoint inhibitors (Nivolumab, Pembrolizumab, Ipilimumab).

Aim: The aim of this paper is to review the metabolic pathways of drugs that have been tested for the treatment of HCC and the potential influence of liver failure over those pathways.

Methods: The Food and Drug Administration (FDA)'s and European Medicines Agency (EMA)'s datasheets, results from clinical trials and observational studies have been reviewed.

Results: This review summarizes the current knowledge regarding targets, metabolic pathways, drug interactions, and adverse events of medical treatments for HCC in cirrhotic patients.

Conclusion: The new scenario of systemic HCC therapy includes more active drugs with different metabolic pathways and different liver adverse events. Clinical and pharmacological studies providing more data on the safety of these molecules are urgently needed.
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http://dx.doi.org/10.2174/1389200221999200918141239DOI Listing
September 2021

Autologous hematopoietic stem cell transplantation following alemtuzumab therapy in aggressive multiple sclerosis: A report of three cases.

Mult Scler 2021 06 25;27(7):1145-1148. Epub 2020 Aug 25.

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa and Ospedale Policlinico San Martino IRCCS, Genoa, Italy.

The management of multiple sclerosis patients with persistent disease activity under alemtuzumab treatment is not established yet. Concerns have been raised on the safety of autologous haematopoietic stem cell transplantation (aHSCT) after alemtuzumab treatment because of the risk of serious infectious adverse events. We report short-term safety and efficacy data from three patients treated with aHSCT following alemtuzumab treatment. Early adverse events were consistent with expected transplant toxicities. All patients were free of disease activity at the last follow-up. Our data suggest that aHSCT can be considered as a rescue treatment strategy for MS patients with persistent disease activity during alemtuzumab treatment.
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http://dx.doi.org/10.1177/1352458520914818DOI Listing
June 2021

Abnormal Papillary Muscle Signal on Cine MRI As a Typical Feature of Mitral Valve Prolapse.

Sci Rep 2020 06 8;10(1):9166. Epub 2020 Jun 8.

Division of Cardiology "Villa dei Fiori" Hospital, Acerra, Na, Italy.

Background: Mitral valve prolapse (MVP) is characterized by an abnormal movement of the valvular apparatus which may affect the papillary muscles (PMs) function and structure. Aim of the study was to investigate abnormal PM signal in MVP by using cardiac magnetic resonance imaging (MRI).

Methods And Results: We enrolled 47 consecutive patients with MVP evaluated by cardiac MRI. Additional groups included healthy volunteers, patients with moderate-to-severe mitral regurgitation (not caused by MVP) and patients with hypertrophic cardiomyopathy. Visual assessment of the PM signals was carried out and the signal intensity (SI) of both the antero-lateral and postero-medial PMs was normalized by that of the left ventricular (LV) parietal myocardium. Our results show that in the MVP group only, the PM signal intensity was significantly lower compared to the one of the LV parietal myocardium. This sign did not correlate with either LV late gadolinium enhancement or positive anamnesis for significant arrhythmias.

Conclusions: In MVP patients only, PM signal is significantly reduced compared to LV parietal myocardium ("darker appearance"). The described findings are not clearly related to evidence of myocardial fibrosis, as assessed by MRI, and to previous occurrence of complex ventricular arrhythmias.
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http://dx.doi.org/10.1038/s41598-020-65983-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7280529PMC
June 2020

Potentially Inappropriate Medications, Drug-Drug Interactions, and Anticholinergic Burden in Elderly Hospitalized Patients: Does an Association Exist with Post-Discharge Health Outcomes?

Drugs Aging 2020 08;37(8):585-593

Unit of Geriatrics, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 200, 00128, Rome, Italy.

Background: Polypharmacy is very common in elderly patients and is associated with detrimental outcomes.

Objective: Our objective was to evaluate the associations between a large panel of therapy quality indicators, including explicit lists of potentially inappropriate medications (PIMs; Beers criteria and Screening Tool of Older Persons' potentially inappropriate Prescriptions [STOPP] criteria), the Anticholinergic Cognitive Burden (ACB) score, and the number of drug-drug interactions (DDIs), with respect to mortality, rehospitalization, and physical function decline within 3 months from hospital discharge in a cohort of hospitalized elderly patients.

Methods: We studied 2631 individuals aged ≥ 65 years (median age 79.6; males 48.6%) enrolled in the REPOSI registry. The relationships with mortality and rehospitalization were evaluated using Cox regressions, and relationships with functional status change (as percentage variation of Barthel Index [BI]) were evaluated using mixed linear models.

Results: None of the studied indicators was associated with mortality and rehospitalization. Conversely, only ACB was associated with physical function decline, even after correction for confounders (adjusted mean BI variation of - 7.55%; 95% confidence interval [CI] - 12.37 to - 2.47). The number of medications at discharge, particularly polypharmacy (more than five drugs daily), were the only therapy-related factors associated with mortality (adjusted hazard ratio [aHR] 1.05 [95% CI 1.01-1.10] and 1.70 [95% CI 1.12-2.58], respectively) and rehospitalization (aHR 1.05 [95% CI 1.01-1.08] and 1.31 [95% CI 1.01-1.71], respectively).

Conclusion: Polypharmacy, a very simple measure, outperformed sophisticated PIM and DDI indicators of quality of therapy as a correlate of primary clinical outcomes, whereas ACB was associated with physical function decline. Thus, innovative approaches to the definition and research of PIMs and DDIs are eagerly awaited from the perspective of averaging the quantitative burden and qualitative interaction of drugs.
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http://dx.doi.org/10.1007/s40266-020-00767-wDOI Listing
August 2020

Hyperreflective Foci in the Retina of Active Relapse-Onset Multiple Sclerosis.

Ophthalmology 2020 12 29;127(12):1774-1776. Epub 2020 Mar 29.

Ophthalmology Clinic, University of Padova, Padova, Italy.

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http://dx.doi.org/10.1016/j.ophtha.2020.03.024DOI Listing
December 2020

Effects of 2-year treatment with dimethyl fumarate on cognition and functional impairment in patients with relapsing remitting multiple sclerosis.

Neurol Sci 2020 Nov 1;41(11):3185-3193. Epub 2020 May 1.

Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari, Bari, Italy.

Background: A significant proportion of patients with multiple sclerosis (MS) show cognitive impairment.

Objective: To evaluate the effect of 2-year treatment with oral dimethyl fumarate (DMF) on cognition in relapsing remitting MS (RRMS).

Methods: In this prospective single-arm study RRMS patients treated with DMF underwent a wide battery of tests, including an extensive neuropsychological evaluation, clinical and patient-reported outcomes (PROs) and quality of life (QoL). Primary endpoints were the proportion of patients with cognitive impairment at baseline and of patients with cognitive worsening over 2 years.

Results: Overall, 217 patients (74.2% females, mean age 37.3 years) receiving DMF were recruited, and 156 (67.2%) completed the study. Of the 49 patients with cognitive impairment at baseline, 34 had 2-year data: 15 (44.1%) patients worsened and 19 (55.9%) did not. The cognitive impairment index improved in one third of patients at 2 years. Less than 20% of patients had relapses at 2 years (annualized relapse rate: 0.190). Few patients had disability progression. PROs (fatigue, depression, impairment in work/social activities), QoL, and most of neuropsychological tests significantly improved vs. baseline.

Conclusion: The 2-year treatment with DMF was associated with slowing of cognitive impairment and with significant improvements in QoL and psychosocial function.
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http://dx.doi.org/10.1007/s10072-020-04320-wDOI Listing
November 2020

Wide Cytokine Analysis in Cerebrospinal Fluid at Diagnosis Identified CCL-3 as a Possible Prognostic Factor for Multiple Sclerosis.

Front Immunol 2020 5;11:174. Epub 2020 Mar 5.

Department of Neurosciences DNS, Multiple Sclerosis Centre, Università degli Studi di Padova, Padua, Italy.

Apart from IgG oligoclonal bands, no other biomarker has, to date, been validated for diagnostic and/or prognostic purposes in multiple sclerosis (MS). To investigate a wide panel of cytokines and chemokines in the cerebrospinal fluid (CSF) of relapsing-remitting MS (RRMS) patients and evaluate their association with clinical and magnetic resonance imaging (MRI) parameters, as well as their predictive clinical value. Fifty-one RRMS at clinical onset and 17 other not inflammatory neurological disorders (ONINDs) underwent brain MRI (including 3D-T1, 3D-FLAIR, and 3-DIR sequences) and CSF examination. Eighty-seven cytokines and chemokines were analyzed in CSF by Multiplex technology. Compared to ONIND, CXCL-10, CXCL-11, CXCL-13, CCL-1, CCL-2, CCL-3, CCL-22, IL-16, and BAFF were significantly ( < 0.05) increased in RRMS CSF. However, only CCL-3 was associated with both MS diagnosis and IgGOB detection. Based on a 95%CI in ONIND (cut-off value: 0.798 pg/ml) and ROC analysis (cut-off value: 0.495 pg/ml), RRMS patients were stratified in CCL-3 (>0.736 pg/mL), CCL-3, and CCL-3 (<0.495 pg/ml). Survival analysis disclosed a strong association between high CCL-3 values and disease reactivation (OR = 4.9, 95%CI: 1.8-13.3, < 0.005) in the following 2 years. CCL-3 deserves further investigation as a candidate prognostic biomarker for RRMS.
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http://dx.doi.org/10.3389/fimmu.2020.00174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7066207PMC
March 2021

Slowly Progressive Optic Perineuritis as the First Clinical Manifestation of Sarcoidosis.

J Neuroophthalmol 2021 03;41(1):e39-e41

Neurology Unit (FG, FR, PP, AM, MM, PG), University Hospital of Padova, Padova, Italy; Neuroradiology Unit (DS), University Hospital of Padova, Padova, Italy; and General Pathology and Cytopathology Unit (MP), Department of Medicine-DIMED, University Hospital of Padova, Padova, Italy.

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http://dx.doi.org/10.1097/WNO.0000000000000924DOI Listing
March 2021

Cerebellar gray matter lesions are common in pediatric multiple sclerosis at clinical onset.

J Neurol 2020 Jun 5;267(6):1824-1829. Epub 2020 Mar 5.

Multiple Sclerosis Centre of the Veneto Region (CeSMuV), University Hospital of Padua, Via Giustiniani 2, 35128, Padua, Italy.

Background: No data are available on the occurrence of gray matter lesions (GML) in the cerebellum of pediatric multiple sclerosis (pedMS).

Objectives: We analyzed frequency, number and topography of GML, and their correlation with cerebellar-related disability in pedMS at clinical onset.

Methods: Fifteen adolescents with pedMS (12F/3M; mean age 14.9 ± 2.2, range 11-17) were studied. Neurological and cognitive evaluations were done by means of EDSS, Trail Making Test-Part B (TMT-B) and Symbol Digit Modalities Test-oral version (SDMT). Cerebellar GML were investigated with double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) sequences obtained with a 3 T-MRI scan.

Results: All patients had white matter lesions (WML) and/or GML in the cerebellum. A significantly higher GML number was observed on PSIR compared to DIR (mean 2.3 ± 2.3 vs 1.1 ± 1.6; median 2.0 (IQR 1.0-2.0) vs 1.0 (IQR 0.0-1.5); p = 0.004). GML were observed in 14/15 (93.3%) patients and were more frequent in the posterior than in the anterior lobe (mean 1.8 ± 2.2 vs 0.47 ± 0.74; median 2.0 (IQR 0.5-2.0) vs 0.0 (IQR 0.0-1.0); p = 0.044). No correlation was found between lesion number or topography and EDSS (r = 0.12, p = 0.69), TMT-B and SDMT.

Conclusion: At clinical onset, cerebellar GML are common in pedMS, are very often asymptomatic, do not correlate with physical and cognitive disability, and more frequently affect the posterior lobe.
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http://dx.doi.org/10.1007/s00415-020-09776-6DOI Listing
June 2020

Design and rationale of the Impact of MultiPoint pacing in CRT patients with reduced RV-to-LV delay (IMAGE-CRT) study.

J Cardiovasc Med (Hagerstown) 2020 Mar;21(3):250-258

Electrophysiology and Cardiac Pacing Unit, Monaldi Hospital, Naples.

Background: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and prolonged QRS duration. A biventricular device is implanted to achieve faster activation and more synchronous contraction of the ventricles. Despite the convincing effect of CRT, 30-40% of patients do not respond. We decided to investigate the role of multipoint pacing (MPP) in a selected group of patients with right ventricle (RV)-to-left ventricle (LV) intervals less than 80 ms that do not respond to traditional CRT.

Methods: We will enrol 248 patients in this patient-blinded, observational, clinical study aiming to investigate if MPP could decrease LV end-systolic volume (ESV) in patients with RV-to-LV interval less than 80 ms. MPP will be activated ON at implant in patients with RV-to-LV delay less than 80 ms and OFF in RV-to-LV at least 80 ms. At follow-up the activation of MPP will be related to CRT response. The primary study endpoint will be the responder rate at 6 months, defined as a decrease in LV ejection fraction, LV end-diastolic volume, LV end-systolic volume (LVESV) at least 15% from baseline. Secondary outcomes include 12 months relative percentage reduction in LVESV and a combined clinical outcome measure of response to CRT defined as the patient being alive, no hospitalization due to heart failure, and experiencing an improvement in New York Heart Association functional class (Composite-Score).

Conclusion: Reducing the nonresponder rate continues to be an important goal for CRT.If an increase in reverse remodelling can be achieved by MPP, this study supports the conduct of larger trials investigating the role of MPP on clinical outcomes in selected patients treated, right now, only with traditional CRT.

Trial Registration: ClinicalTrials.gov, NCT02713308. Registered on 18 March 2016.
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http://dx.doi.org/10.2459/JCM.0000000000000928DOI Listing
March 2020

Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis.

Cerebellum 2020 Apr;19(2):192-200

Multiple Sclerosis Centre of the Veneto Region, Padua, Italy.

Cerebellar dysfunctions have been associated to depressive disorders and cognitive impairment in neurodegenerative diseases. The objective is to analyze the associations between cerebellar atrophy, depression, and fatigue in the early phases of relapse-onset multiple sclerosis (RRMS). Sixty-one RRMS patients and 50 healthy controls (HC) were enrolled and clinically evaluated by means of expanded disability status scale (EDSS), Rao's brief repeatable battery of neuropsychological tests (BRB-NT), Delis-Kaplan executive function system sorting test, beck depression inventory II (BDI-II), and fatigue severity scale (FSS). The relationships between MRI variables and clinical scores were assessed. Depressed RRMS (dRRMS) had significantly lower Vermis Crus I volume compared with not depressed RRMS (ndRRMS) (p = 0.009). Vermis Crus I volume was lower in dRRMS suffering from fatigue than in ndRRMS without fatigue (p = 0.01). The hierarchical regression models which included demographic and clinical data (age, sex, and disease duration, FSS or BDI-II) and cerebellar volumes disclosed that cerebellar lobule right V atrophy explained an increase of 4% of the variability in FSS (p = 0.25) and Vermis Crus I atrophy explained an increase of 6% of variability in BDI-II (p = 0.049). Since clinical onset, atrophy of specific cerebellar lobules associates with important clinical aspects of RRMS. Cerebellar pathology may be one of the determinants of fatigue and depression that contribute to worsen disability in RRMS.
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http://dx.doi.org/10.1007/s12311-019-01096-4DOI Listing
April 2020

Diagnostic value of Virtual Touch Quantification (VTQ®) for differentiation of hemangiomas from malignant focal liver lesions.

Med Ultrason 2019 Nov;21(4):371-376

Hepatology and Clinical Medicine Unit of University Campus Bio Medico of Rome.

Aim: To evaluate the diagnostic value of Virtual Touch Quantification (VTQ®) for characterizing benign vs. malignant focal liver lesions (FLLs).

Material And Methods: From January 2015 to January 2016 all consecutive FLLs visualized during a conventional abdominal ultrasound (US), underwent VTQ® evaluation, taking five measurements of both the lesion and the surrounding parenchyma.

Results: We studied 119 FLLs, consisting of 52 hemangiomas (HEs), 39 hepatocellular carcinomas (HCCs), and 28 liver metastases (METs). HEs showed a significantly lower shear wave velocity (SWV) values compared to malignant FLLs (HEs SWV median value 1.34 m/sec, IQR 0.9; malignant lesions SWV median value 2.69 m/sec, IQR 1.6; p<0.001). Moreover, a nodule-to-parenchyma SWV ratio showed a significant difference in HEs and METs (p<0.001) but not in HCCs (p=0.03). SWV values were able to correctly differentiate malignant lesions with c-statistics of 0.82 (95 % CI 0.74- 0.90) and sensitivity of 74.6%/specificity of 80.7% at a cut-off of 2 m/sec.

Conclusions: Our results suggest that VTQ® is able to distinguish HEs from malignant lesions (HCCs and METs) at a SWV cut-off of 2 m/sec.
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http://dx.doi.org/10.11152/mu-2062DOI Listing
November 2019

Correction to: Aging with multiple sclerosis: prevalence and profile of cognitive impairment.

Neurol Sci 2020 Jan;41(1):243

Department NEUROFARBA, Section Neurosciences, University of Florence, Largo Brambilla 3, 50134, Florence, Italy.

The above article was published online with an error in author name's affiliation. The Author Claudia Niccolai has changed her affiliation to IRCCS Fondazione Don Carlo Gnocchi, Florence, Italy.
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http://dx.doi.org/10.1007/s10072-019-04134-5DOI Listing
January 2020

Molecular imaging of multiple sclerosis: from the clinical demand to novel radiotracers.

EJNMMI Radiopharm Chem 2019 Apr 8;4(1). Epub 2019 Apr 8.

Nuclear Medicine Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132, Genoa, Italy.

Background: Brain PET imaging with different tracers is mainly clinically used in the field of neurodegenerative diseases and brain tumors. In recent years, the potential usefulness of PET has also gained attention in the field of MS. In fact, MS is a complex disease and several processes can be selected as a target for PET imaging. The use of PET with several different tracers has been mainly evaluated in the research setting to investigate disease pathophysiology (i.e. phenotypes, monitoring of progression) or to explore its use a surrogate end-point in clinical trials.

Results: We have reviewed PET imaging studies in MS in humans and animal models. Tracers have been grouped according to their pathophysiological targets (ie. tracers for myelin kinetic, neuroinflammation, and neurodegeneration). The emerging clinical indication for brain PET imaging in the differential diagnosis of suspected tumefactive demyelinated plaques as well as the clinical potential provided by PET images in view of the recent introduction of PET/MR technology are also addressed.

Conclusion: While several preclinical and fewer clinical studies have shown results, full-scale clinical development programs are needed to translate molecular imaging technologies into a clinical reality that could ideally fit into current precision medicine perspectives.
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http://dx.doi.org/10.1186/s41181-019-0058-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6453990PMC
April 2019
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