Leader: Stefania Basili (SAPIENZA); Other collaborator(s):
The integration of sex and gender provides new opportunities for understanding disease progression. This task will introduce the dimensions of gender to the Frailty Index. Gender-sensitive domains (sex, identity, roles, relations, institutionalized, social, behavioral) are binding modifiers of multimorbidity outcomes. The task will develop tools to decode the gender effect on aging trajectories. Milestones are: 1) identification (post-hoc analysis) of gender-specific factors linked to frailty; 2) generation of the gender frailty index (GFI) for patients admitted to internal medicine/geriatric wards; 3) validation of gender-sensitive tools to tailor social- and health-related interventions during and after hospitalization.
Brief description of the activities and of the intermediate results: To provide a framework to assess sex and gender effect in ageing research, the BASILI Unit UniRoma1 designed a multicenter nationwide observational prospective cohort study to collect data for the construction of a sex and gender-sensitive frailty index, the gender frailty index (GFI). Ethical Approval has been obtained as coordinating center and a list of at least 40 centers have been identified among geriatrics and internal medicine units (target population: 1000 old adult hospitalized). To reflect the knowledge advancements in the field of gender methods and measure along the 2023, an implemented version of the gender-specific questionnaire has been developed.
To identify novel sex/gender-specific thrombo-inflammatory markers of frailty, pilot studies on older individuals at high cardiovascular risk (e.g. atrial fibrillation, dyslipidaemia, etc) were performed and preliminary Interim analyses revealed interesting findings that have been submitted as abstracts for international congress (European Society of Cardiology - ESC Congress 2024). Specifically,
1. Dysfunctional mitochondria in circulating platelets from individuals with atrial fibrillation: a pilot study
2. The interplay between IL18 and NETosis varies across the continuum of ischemic heart disease
3. Platelet biomarkers and sociocultural gender: insights from the EVA study. 4 original articles were published in 2023: (doi:10.1007/s00392-023-02193-5; doi.org/10.3390/nu15143150; doi.org/10.3390/jpm13071155; doi: 10.3390/ijms242417429.)
Main policy, industrial and scientific implications: The development of sex and gender-sensitive tools in clinical practice is a very much needed unmet goal. Therefore, the development of shared framework to assess sex and gender effect in ageing research will lead to a more precise and personalized approach for an adequate and equitable assessment of frailty in older adults. This activity is aligned with the WHO Sustainable Development Goals, number 3 (Good Health and Well-Being) and 5 (Gender Equality).
- Set up of institutional operative email for the project (age-it.dmtp@uniroma1.it).
- Narrative revision of the literature on sex and gender specific aspects in the clinical trial using available frailty tools (time frame 2001-2023)
- Set up for the RED CAP case report form for the multicenter study with Institutional Referee at Sapienza University of Rome.
- On-going measurement of biomarkers of thrombo-inflammation and mitochondrial dysfunction in high risk aged frail patients (including patient with atrial fibrillation and with MASLD).
- Drafting manuscript for submission (“Sex and Gender Specific Clinical Considerations in Frailty: The Past, the Present and the Future”) .
- Feasibility trial of the red cap case form report for prospective study.
- Data analysis/Assessment of findings on: Multiparametric platelet phenotyping of aged patients with and without cardiac arrhythmia
- Drafting manuscript and submission of manuscript: A potential age-independent MASLD-related liver fibrosis index reflecting gut dysbiosis and hepatic stellate cells reprogramming.
- Ethical committee approval for the amendment to the study protocol (Prot. 0861/2024)
- Changes to the Red Cap case form report after feasibility trial, new testing.
- Identification of 50 centers likely recruiting centers
- Knowledge Translation Activities:
- 125° Italian Society of Internal Medicine (Rimini, 12-14 October) - presentation of scientific output [oral communication - Buoninfante G et al. - Dysfunctional mitochondria in circulating platelets from individuals with atrial fibrillation: a Pilot study: abstracts: i) The interplay between platelet and socio-cultural gender: a report from the EVA study (D'Amico T et al.); and ii) the proinflammatory role of NETs in ischemic heart disease 8miglionico M et al.].
- National Conference– Geriatrics and Sapienza (Geriatria e Sapienza), December 6-7, Basili S invited chairwoman Session “Gender medicine in Geriatrics” - first presentation and release of call for interest to participate the nationwide multi-center observational study aimed at identifying the gender frailty index (GFI) (Sapienza docet: how gender medicine has changed over time - V. Raparelli)
- Drafting and submission of the following manuscripts: “Distinct platelet phenotype and reactivity in individuals with permanent atrial fibrillation treated with direct oral anticoagulants: a pilot study” and “ Changes of in-vivo markers of platelet activation during the menstrual cycle in healthy pre-menopausal women: insights from the SHOW study”
- Spoto S, Basili S, Cangemi R, Yuste JR, Lucena F, Romiti GF, Raparelli V, Argemi J, D'Avanzo G, Locorriere L, Masini F, Calarco R, Testorio G, Spiezia S, Ciccozzi M, Angeletti S. A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections. Cells. 2024;13(11):892. doi: 10.3390/cells13110892. PMID: 38891025; PMCID: PMC11172186.
- Anna Morrone , Valerio Fiorilli , Lilia Cinti , Piergiorgio Roberto , Alejandro Luis Ferri , Marcella Visentini , Aessandro Pulsoni , Francesca Romana Spinelli , Adriano De Santis , Guido Antonelli, Stefania Basili , Maria Elena Tosti ,Fabrizio Conti and Milvia Casato. Surface antigen serocleared hepatitis B virus infection increases the risk of mixed cryoglobulinemia vasculitis in male patients with chronic hepatitis C. Frontiers in Immunology 2024 (Accepted)
- La Gualana F, Olivieri G, Petriti B, Picciariello L, Natalucci F, Sciannamea M, Gragnani L, Basile U, Casato M, Spinelli FR, Stefanini L, Basili S, Visentini M, Ceccarelli F, Conti F. Early decrease of T-bet<sup>+</sup> B cells during subcutaneous belimumab predicts response to therapy in systemic lupus erythematosus patients. Immunol Lett. 2024 Dec 4;272:106962. doi: 10.1016/j.imlet.2024.106962.