Exploring serum and CSF Calcitonin Gene Related Peptide levels: A promising biomarker in multiple sclerosis?

Introduction: Calcitonin Gene Related Peptide (CGRP) is a neuropeptide ubiquitous in the peripheral and central nervous system, mostly known for the role in vasodilation and pain signal transmission during migraine attacks. Recent studies have been unraveling its immunomodulatory properties, including its possible role in multiple sclerosis (MS) pathophysiology, however there is no conclusive evidence on whether it plays a pro or anti-inflammatory role. Objectives/Aims: To evaluate soluble CGRP levels at MS diagnosis, in cerebrospinal fluid (CSF) and serum, and evaluate associations with progression and short-term disease severity. Methods: We enrolled for a retrospective cohort study 59 patients (39 females, mean age at diagnosis 38.79 years ± standard deviation or SD 9.89) with Radiological Isolated Syndrome (RIS), Clinical Isolated Syndrome (CIS) and Relapsing-Remitting (RR) MS. During the diagnostic work-up were collected clinic-demographic data, serum and CSF. Patients were followed with clinical visits in which clinical data were collected.*** CGRP levels were determined through an ELISA commercial kit (MyBioSource Inc, MBS267126, San Diego, CA, USA). None had a history of migraine attack at diagnosis. Statistical analyses were conducted with STATA software to determine Mann–Whitney, Kruskal-Wallis test and Spearman’s rank correlation coefficient significance. Results: CGRP levels were significantly higher in MS patients if compared to healthy controls published by Papiri et Al. (PMID: 37013432) and Han et Al. (PMID: 35204700). Mean values resulted 73.10 pg/ml in serum (±9.42 vs 29.50 ± 8.91, p<0.05 t-test) and 64.01 in CSF (± 10.39 vs 52.05 ± 5.70, p<0.05 t-test). CGRP levels did not relate to clinical variables at diagnosis: age, gender, Expanded Disability Status Scale (EDSS), number of T2, gadolinium enhancing and spinal cord lesions. However, there was a positive correlation between serum CGRP and the Multiple Sclerosis Severity Score (MSSS) at the last follow up (r2 = 0.27, p<0.05 Spearman’s rank correlation). Conclusion: We observed an increased CGRP level in the CSF and serum of MS patients at diagnosis. Our findings suggest its potential use as a biomarker to identify cases with poor prognosis, indicating a pro-inflammatory effect of this neuropeptide

Gas6/TAM system: potential prognostic biomarker for Multiple Sclerosis

Introduction: The protein growth arrest specific 6 (Gas6) and its tyrosine kinase receptors Tyro-3, Axl, Mer (TAMs) are ubiquitous proteins involved in regulation of inflammation and apoptotic body clearance. Gas6 and TAMs have been associated with neuronal remyelination and stimulation of oligodendrocyte survival. However, few data are available on their role in multiple sclerosis (MS). Objectives/Aims: Objectives/Aims: In this study we evaluated if soluble levels of these molecules, determined at MS diagnosis in cerebrospinal fluid (CSF) and serum, correlated with progression with short-term disease severity. Methods: Methods: We conducted a retrospective cohort study enrolling 64 patients with different forms of MS, the Radiological Isolated Syndrome (RIS), the Clinical Isolated Syndrome (CIS) and Relapsing-Remitting (RR). At diagnosis, we collected serum, CSF, and clinical-radiological data: lesion load, spinal cord, and gadolinium-enhancing (Gad+) lesions, and expanded disability status score (EDSS). During the last clinical follow-up EDSS, MS severity score (MSSS) and Age-Related MS severity (ARMSS) were assessed. Gas6 and TAMs were determined by ELISA kit (R&D Systems), while neurofilaments (NFLs) levels, for neuronal damage assessment, by SimplePlexTM fluorescence-based immunoassay. Statistical analyses were conducted with STATA software to determine Mann–Whitney, Kruskal-Wallis test and Spearman’s rank correlation coefficient significance. Results: Results: At diagnosis, RIS and CIS showed higher values of sMer and sTyro-3, compared to RRMS (p = 0.007 and p = 0.018). Serum sAxl was higher in patients untreated or first-line disease modifying treatments (DMTs) versus patients with high-efficacy DMTs (p = 0.04). Moreover, serum Axl was associated with EDSS ≤ 3 at diagnosis (p = 0.037) and EDSS progression in patients with EDSS ≤ 3 (p = 0.017). Similarly, high levels of Gas6 in CSF were associated with EDSS ≤ 3 at diagnosis (p = 0.04), and high levels of Gas6 in serum to a lower MSSS (r2 = -0.32 and p = 0.01). Results significances were confirmed by multivariate analyses. In our cohort, serum and CSF NFLs levels were confirmed as markers of disability in EDSS (p = 0.005 and p = 0.002) and MSSS (r2 = 0.27 and p =0.03; r2 = 0.39 and p = 0.001). Conclusion: Conclusion: Taken together, our results suggest that Gas6 and its receptors, particularly Axl, might have a neuroprotective role and prognostic potential in MS. Disclosures: Disclosures: Nothing to disclos

Integrated forest management to prevent wildfires under Mediterranean environments

This review presents a multidisciplinary framework for integrating the ecological, regulatory, procedural and technical aspects of forest management for fi res prevention under Mediterranean environments. The aims are to: i) provide a foreground of wildfi re scenario; ii) illustrate the theoretical background of forest fuel management; iii) describe the available fuel management techniques and mechanical operations for fi re prevention in forest and wildland-urban interfaces, with exemplifi cation of case-studies; iv)allocate fi re prevention activities under the hierarchy of forest planning. The review is conceived as an outline commentary discussion targeted to professionals, technicians and government personnel involved in forestry and environmental management

Baseline Plasma Osteopontin Protein Elevation Predicts Adverse Outcomes in Hospitalized COVID-19 Patients

More than three years have passed since the first case, and COVID-19 is still a health concern, with several open issues such as the lack of reliable predictors of a patient's outcome. Osteopontin (OPN) is involved in inflammatory response to infection and in thrombosis driven by chronic inflammation, thus being a potential biomarker for COVID-19. The aim of the study was to evaluate OPN for predicting negative (death or need of ICU admission) or positive (discharge and/or clinical resolution within the first 14 days of hospitalization) outcome. We enrolled 133 hospitalized, moderate-to-severe COVID-19 patients in a prospective observational study between January and May 2021. Circulating OPN levels were measured by ELISA at admission and at day 7. The results showed a significant correlation between higher plasma concentrations of OPN at hospital admission and a worsening clinical condition. At multivariate analysis, after correction for demographic (age and gender) and variables of disease severity (NEWS2 and PiO2/FiO2), OPN measured at baseline predicted an adverse prognosis with an odds ratio of 1.01 (C.I. 1.0-1.01). At ROC curve analysis, baseline OPN levels higher than 437 ng/mL predicted a severe disease evolution with 53% sensitivity and 83% specificity (area under the curve 0.649, p = 0.011, likelihood ratio of 1.76, (95% confidence interval (CI): 1.35-2.28)). Our data show that OPN levels determined at the admission to hospital wards might represent a promising biomarker for early stratification of patients' COVID-19 severity. Taken together, these results highlight the involvement of OPN in COVID-19 evolution, especially in dysregulated immune response conditions, and the possible use of OPN measurements as a prognostic tool in COVID-19

The impact of puberty on the onset, frequency, location, and severity of attacks in hereditary angioedema due to C1-inhibitor deficiency: A survey from the Italian Network for Hereditary and Acquired Angioedema (ITACA)

IntroductionHereditary angioedema due to C1-inhibitor deficiency is influenced by hormonal factors, with a more severe course of disease in women. Our study aims to deepen the impact of puberty on onset, frequency, location and severity of attacks.MethodsRetrospective data were collected through a semi-structured questionnaire and shared by 10 Italian reference centers of the Italian Network for Hereditary and Acquired Angioedema (ITACA).ResultsThe proportion of symptomatic patients increased significantly after puberty (98.2% vs 83.9%, p=0.002 in males; 96.3% vs 68,4%, p&lt;0.001 in females); the monthly mean of acute attacks was significantly higher after puberty, and this occurred both in females (median (IQR) = 0.41(2) in the three years before puberty vs 2(2.17) in the three years after, p&lt;0.001) and in males (1(1.92) vs 1.25(1.56) respectively, p&lt;0.001). The increase was greater in females. No significant differences were detected in attack location before and after puberty.DiscussionOverall, our study confirms previous reports on a more severe phenotype in the female gender. Puberty predisposes to increased numbers of angioedema attacks, in particular in female patients

Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

: As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

The “Diabetes Comorbidome”: A Different Way for Health Professionals to Approach the Comorbidity Burden of Diabetes

(1) Background: The disease burden related to diabetes is increasing greatly, particularly in older subjects. A more comprehensive approach towards the assessment and management of diabetes’ comorbidities is necessary. The aim of this study was to implement our previous data identifying and representing the prevalence of the comorbidities, their association with mortality, and the strength of their relationship in hospitalized elderly patients with diabetes, developing, at the same time, a new graphic representation model of the comorbidome called “Diabetes Comorbidome”. (2) Methods: Data were collected from the RePoSi register. Comorbidities, socio-demographic data, severity and comorbidity indexes (Cumulative Illness rating Scale CIRS-SI and CIRS-CI), and functional status (Barthel Index), were recorded. Mortality rates were assessed in hospital and 3 and 12 months after discharge. (3) Results: Of the 4714 hospitalized elderly patients, 1378 had diabetes. The comorbidities distribution showed that arterial hypertension (57.1%), ischemic heart disease (31.4%), chronic renal failure (28.8%), atrial fibrillation (25.6%), and COPD (22.7%), were the more frequent in subjects with diabetes. The graphic comorbidome showed that the strongest predictors of death at in hospital and at the 3-month follow-up were dementia and cancer. At the 1-year follow-up, cancer was the first comorbidity independently associated with mortality. (4) Conclusions: The “Diabetes Comorbidome” represents the perfect instrument for determining the prevalence of comorbidities and the strength of their relationship with risk of death, as well as the need for an effective treatment for improving clinical outcomes