AB0844 HAND GRIP STRENGTH EVALUATION IN RHEUMATOLOGIC DISEASES

Background:Handgrip muscle strength test describes the strength of the hand muscles used to grasp or grip. Currently, hand grip evaluation is often used in clinical practice, as a marker of function and disability. In fact, it has already been applied as an outcome measure in arthritis rheumatoid clinical trials, to demonstrate the benefits of several treatments [1]. However, hand disability should also be considered in all other rheumatological diseases.Objectives:The main aim of this study is to assess the handgrip muscle strength test in a rheumatological cohort of patients as compared to a control group.Methods:This is a cross-sectional pilot study. We considered eligible 35 rheumatological consecutive female patients followed at our outpatients' clinic of Internal Medicine (I Policlinico of Naples) and 35 healthy control females (HC). Both groups included only right-handed individuals. Rheumatological patients were distributed as follows: 5 rheumatoid arthritis (14,3%), 9 psoriatic arthritis (25,7%), 4 systemic lupus erythematosus (11,4%), 10 systemic sclerosis (28,6%), 4 fibromyalgia (11,4%), 3 juvenile idiopathic arthritis (8,6%). The course of disease was under optimal treatment in all patients.The type of hand grip used is the power grip, in which an object is held firmly by wrapping the fingers around it, pressing the object against the palm, and using the thumb to apply counter-pressure. We considered as either right or left hand valid measure the mean of three consecutive tests per arm. Between-groups differences were tested both by a uni- and multivariable analysis.Results:The two subgroups were homogeneously distributed for age (median age 42 yrs. [IQR 33-48] vs. 36 yrs. [IQR 30-52] in HC; p=0.902). At univariate analysis, hand grip strength was significantly lower in the rheumatological patients, both at right hand (right 19.5 kg [IQR 13.6-24.8] vs. 24.5 kg [IQR 20.8-29] in HC; p=0.004) and left hand (18.5 kg [IQR 13.9-22.5] vs. 23.7 kg [IQR 19-27.3] in HC; p=0.002), as compared to HC. This finding was further confirmed at multivariable analysis only as for the left hand (OR 0.919, 95%CI: 0.858-0.984; p=0.016).Conclusion:Rheumatological diseases are burdened by hand disability, mostly affecting daily activities performance [2,3]. Beyond an optimal disease control, our pilot study shows a decrease in left hand strength as compared to healthy controls. This might be due to a reduced use of the non-dominant hand, which may lead over time to a higher deficit of strength. As such, these patients should be prescribed to a left hand exercise to improve both mobility and strength and, consequently, hand function.References:[1]Eberhardt K, Sandqvist G, Geborek P (2008) Hand function tests are important and sensitive tools for assessment of treatment response in patients with rheumatoid arthritis. Scand J Rheumatol 37(2):109–112.[2]Feced Olmos CM, Alvarez-Calderon O, Hervás Marín D, et al. Relationship between structural damage with loss of strength and functional disability in psoriatic arthritis patients. Clin Biomech (Bristol, Avon). 2019 Aug;68:169-174. doi: 10.1016/j.clinbiomech.2019.06.009.[3]Maddali-Bongi S, Del Rosso A, Mikhaylova S, et al. Impact of hand and face disabilities on global disability and quality of life in systemic sclerosis patients. Clin Exp Rheumatol. 2014 Nov-Dec;32(6 Suppl 86):S-15-20.Disclosure of Interests:None declare

The Role of Neuropathy Screening Tools in Patients Affected by Fibromyalgia

Fibromyalgia syndrome (sFM) is one of the most common causes of chronic pain. This study aimed to assess the presence of small and large fiber impairment in fibromyalgic patients by applying validated scores used in the screening for diabetic neuropathy. The endpoints for the study were the assessment of neuropathy prevalence in sFM patients using the NerveCheck Master (NCM), the Michigan Neuropathy Screening Instrument (MNSI), the Diabetic Neuropathy Symptom (DNS) and the Douleur Neuropathique 4 Questions (DN4). The sample was composed of 46 subjects: subjects with sFM (n = 23) and healthy controls (HC) (n = 23). The positivity rates in each group for DN4 were significantly different (p < 0.001), with a prevalence in symptomatic subjects of 56.3% (n = 9) among sFM individuals. A similar difference was also observed with the DNS total score (p < 0.001). NCM and MNSI did not disclose significant differences between the two groups. This finding seems to confirm the data regarding the prevalence of a neuropathic pain in sFM patients

The Diabetic Cardiomyopathy: The Contributing Pathophysiological Mechanisms

Individuals with diabetes mellitus (DM) disclose a higher incidence and a poorer prognosis of heart failure (HF) than non-diabetic people, even in the absence of other HF risk factors. The adverse impact of diabetes on HF likely reflects an underlying “diabetic cardiomyopathy” (DM–CMP), which may by exacerbated by left ventricular hypertrophy and coronary artery disease (CAD). The pathogenesis of DM-CMP has been a hot topic of research since its first description and is still under active investigation, as a complex interplay among multiple mechanisms may play a role at systemic, myocardial, and cellular/molecular levels. Among these, metabolic abnormalities such as lipotoxicity and glucotoxicity, mitochondrial damage and dysfunction, oxidative stress, abnormal calcium signaling, inflammation, epigenetic factors, and others. These disturbances predispose the diabetic heart to extracellular remodeling and hypertrophy, thus leading to left ventricular diastolic and systolic dysfunction. This Review aims to outline the major pathophysiological changes and the underlying mechanisms leading to myocardial remodeling and cardiac functional derangement in DM-CMP

Efficacy of COVID-19 vaccination in patients with immune system disorders and cancer

This is an editorial on the efficacy of COVID-19 vaccines in immune system disorders and cancer

An Overview of the Cardiorenal Protective Mechanisms of SGLT2 Inhibitors

Sodium-glucose co-transporter 2 (SGLT2) inhibitors block glucose reabsorption in the renal proximal tubule, an insulin-independent mechanism that plays a critical role in glycemic regulation in diabetes. In addition to their glucose-lowering effects, SGLT2 inhibitors prevent both renal damage and the onset of chronic kidney disease and cardiovascular events, in particular heart failure with both reduced and preserved ejection fraction. These unexpected benefits prompted changes in treatment guidelines and scientific interest in the underlying mechanisms. Aside from the target effects of SGLT2 inhibition, a wide spectrum of beneficial actions is described for the kidney and the heart, even though the cardiac tissue does not express SGLT2 channels. Correction of cardiorenal risk factors, metabolic adjustments ameliorating myocardial substrate utilization, and optimization of ventricular loading conditions through effects on diuresis, natriuresis, and vascular function appear to be the main underlying mechanisms for the observed cardiorenal protection. Additional clinical advantages associated with using SGLT2 inhibitors are antifibrotic effects due to correction of inflammation and oxidative stress, modulation of mitochondrial function, and autophagy. Much research is required to understand the numerous and complex pathways involved in SGLT2 inhibition. This review summarizes the current known mechanisms of SGLT2-mediated cardiorenal protection

Current hepatocellular carcinoma systemic pharmacological treatment options

Liver cancer is the sixth common cancer and the second leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) accounts for ~90% of cases of liver cancer and is the fourth most common cause of cancer-related death in the world. Up to now, 4 oral multityrosine kinase inhibitors (sorafenib, lenvatinib, regorafenib and cabozantinib), 1 anti-angiogenic antibody (ramucirumab) and 5 immune checkpoint inhibitors, alone or in combination (atezolizumab in combination with bevacizumab, ipilimumab in combination with nivolumab, tremelimumab in combination with durvalumab, nivolumab and pembrolizumab in monotherapy) have been commercialized for advanced HCC patients’ treatment. The aim of this editorial is to provide an insight in current hepatocellular carcinoma systemic pharmacological treatment options

Impact of chronic liver disease upon admission on COVID-19 in-hospital mortality: Findings from COVOCA study

Background Italy has been the first Western country to be heavily affected by the spread of SARS-COV-2 infection and among the pioneers of the clinical management of pandemic. To improve the outcome, identification of patients at the highest risk seems mandatory. Objectives Aim of this study is to identify comorbidities and clinical conditions upon admission associated with in-hospital mortality in several COVID Centers in Campania Region (Italy). Methods COVOCA is a multicentre retrospective observational cohort study, which involved 18 COVID Centers throughout Campania Region, Italy. Data were collected from patients who completed their hospitalization between March-June 2020. The endpoint was in-hospital mortality, assessed either from data at discharge or death certificate, whilst all exposure variables were collected at hospital admission. Results Among 618 COVID-19 hospitalized patients included in the study, 143 in-hospital mortality events were recorded, with a cumulative incidence of about 23%. At multivariable logistic analysis, male sex (OR 2.63, 95%CI 1.42–4.90; p = 0.001), Chronic Liver Disease (OR 5.88, 95%CI 2.39–14.46; p<0.001) and malignancies (OR 2.62, 95%CI 1.21–5.68; p = 0.015) disclosed an independent association with a poor prognosis, Glasgow Coma Scale (GCS) and Respiratory Severity Scale allowed to identify at higher mortality risk. Sensitivity analysis further enhanced these findings. Conclusion Mortality of patients hospitalized for COVID-19 appears strongly affected by both clinical conditions on admission and comorbidities. Originally, we observed a very poor outcome in subjects with a chronic liver disease, alongside with an increase of hepatic damage

Efficacy and durability of multifactorial intervention on mortality and MACEs:a randomized clinical trial in type-2 diabetic kidney disease

Background: Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods: Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and < 175 mg/dL, respectively). Primary endpoint was MACEs occurrence by end of follow-up phase. Secondary endpoints included single components of primary endpoint and all-cause death. Results: At the end of intervention period (median 3.84 and 3.40 years in MT and SoC group, respectively), targets achievement was significantly higher in MT. During 13.0 years (IQR 12.4–13.3) of follow-up, 262 MACEs were recorded (116 in MT vs. 146 in SoC). The adjusted Cox shared-frailty model demonstrated 53% lower risk of MACEs in MT arm (adjusted HR 0.47, 95%CI 0.30–0.74, P = 0.001). Similarly, all-cause death risk was 47% lower (adjusted HR 0.53, 95%CI 0.29–0.93, P = 0.027). Conclusion: MT induces a remarkable benefit on the risk of MACEs and mortality in high-risk DKD patients. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT0053592

Discovering reflected cross-site scripting vulnerabilities using a multiobjective reinforcement learning environment

Tools that automate testing of web applications for Cross-Site Scripting (XSS) vulnerabilities perform well when they have a strong knowledge base. Though, they heavily rely on brute force, which is not always an effective choice. On the other hand, expert penetration testers adopt exploit methods that are more accurate, but often not structured. We propose to solve the above mentioned problems, by designing and implementing an intelligent agent, called Suggester, that recommends actions to penetration testers. First, a black-box testing methodology inspired by a penetration tester's behavior, is developed. Such methodology consists of sending a sequence of strings to a web application and observing the responses. Then, an agent is trained to produce attack strings using the framework of a Multiobjective Reinforcement Learning environment (MORL), with a parameterized action space. Each complete attack string is identified as a separate objective to reach. Q-Learning is used to train the agent upon separate, unrelated objectives. Then, the learned actions are suggested to a human-in-the-loop, who performs the actions and collects observations. This allows to orchestrate the agent into pursuing the right objective and selecting the next best action to recommend. The final evaluation proves the scalability of the proposed solution, as well as show an increase in accuracy when compared to other automated scanners

Capturing flags in a dynamically deployed microservices-based heterogeneous environment

Increasing security awareness is a popular defense strategy adopted by companies against cyber attacks. Testbeds that support the so called cybersecurity exercises, strongly rely on virtualization technologies to faithfully reproduce real world scenarios. OS virtualization has proved to be a good solution to improve scalability, but it draws the line on the categories of reproducible vulnerabilities. In this paper, we tackle the challenges arising from the introduction of OS virtualization. We propose a solution that allows to rely as much as possible on the use of containers, as well as integrate them with legacy virtualization approaches when the vulnerabilities to be emulated do not lend themselves to a container-based implementation. We use the Infrastructure-as-Code (IaC) paradigm to enable automation of both provisioning and configuration of the emulated scenarios, as well as integrate heterogeneous virtualization technologies. After showing the design and implementation of the proposed solution, we discuss how our approach leverages a cyber range instantiation platform, that can be designed and tested on a single laptop, before being deployed on an enterprise system infrastructure