La Batie Rolland, France

A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome

Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI) Score Evolution: Identification of Cardiovascular Risk in Patients with Heart Failure

Heart failure is a complex condition affecting multiple organs beyond the cardiovascular system, influencing disease progression and prognosis. It has become increasingly evident that accurate risk assessment requires considering multiple variables, as no single parameter alone is sufficient for prognosis. These findings have led to the identification and study of prognostic parameters that, when combined, allow for a more precise risk estimation and identification of high-risk patients. Various prognostic scores have been developed, utilizing algorithms that integrate multiple variables to estimate an individual's mortality risk. Some scores are based on clinical evaluation and comorbidities, others on laboratory findings, baroreflex sensitivity, heart rate, sleep abnormalities, echocardiographic imaging, or cardiopulmonary exercise testing (CPET), either alone or in combination with other factors. CPET provides several parameters strongly correlated with prognosis. Since the 1990s, its use-alongside clinical data-has been recommended in heart failure management guidelines. More recently, in addition to peak oxygen consumption, the VE/VCO₂ slope has been recognized as a key prognostic marker, reflecting ventilatory efficiency and ventilation-perfusion mismatch, and has been included in heart transplant assessment criteria. Current risk models in heart failure often omit important prognostic parameters, such as ventilatory indices from CPET, renal function, and hemoglobin levels. Among the numerous prognostic scores available, only the HF Survival Score (HFSS) and the HF Action Predictive Risk Score Model incorporate exercise-related parameters (peak VO₂ in the former and exercise duration in the latter), yet both neglect ventilatory aspects. Even the widely used Seattle Score does not include exercise-related variables. In 2012, the researchers developed the MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) score, integrating oxygen consumption, ventilatory efficiency, and easily accessible biochemical and echocardiographic parameters. Unlike previous models requiring extensive data collection, MECKI is based on just six key variables, making it both practical and effective. Recent studies indicate the need to review and update the cutoff values and parameters used in prognostic models, as the introduction of new therapies and treatment strategies may significantly impact their predictive power in specific patient populations. Study Objectives and Purpose The aim of this study is to expand and update the patient dataset to further develop the MECKI score, optimizing its application in patient subgroups and adapting it to new therapies and treatments introduced in clinical practice. Additionally, the researchers seek to determine whether risk prediction accuracy varies in advanced-stage patients, those with comorbidities, or those receiving different treatments. This could lead to the development of correction factors for the MECKI score, improving its predictive power and applicability across different clinical scenarios. Study Population Patients with systolic heart failure, consecutively enrolled and followed at multiple Heart Failure Units across Italy. Patients undergo assessment through medical history collection, physical examination, laboratory tests, ECG, transthoracic echocardiography, and cardiopulmonary exercise testing (CPET). Follow-up will be conducted according to the protocol of the respective Heart Failure Unit. The follow-up period ends at the last evaluation at the reference center, or upon the patient's death or heart transplantation.

Italian PheNotypes Obstructive Sleep Apnea Study

Obstructive Sleep Apnea (OSA) is the most common sleep-related breathing disorder, representing a major socioeconomic burden on healthcare systems worldwide. Studies performed in Europe in the last twenty years showed a very high prevalence and highlighted that the severity of untreated OSA worsens over time. OSA is associated also with an increased risk to develop cardiovascular, cerebrovascular and metabolic diseases. Finally, recent studies reported a very high mortality in untreated OSA patients, including those with mild severity. Data on European population have been obtained by the "ESADA group" (European Sleep Apnea Database), a consortium of 25 sleep center across Europe that includes three Italian Research Hospitals. The ESADA showed significant differences between European geographical macrozones in terms of symptoms and complications. However, no data are available for the Italian population in terms of prevalence, clinical presentation and comorbidities. The present project aims to overcome this limitation by obtaining a more defined picture of OSA in Italy. A cohort study was designed in collaboration with the Sleep Centers endorsed by the Italian Scientific Society of Sleep Medicine (AIMS). Aims of the present project are to: 1. Assess the distribution different physiological (endotypes) and clinical patterns (phenotypes) of OSA in Italian patients 2. Analyze the association between OSA and co-morbidities by taking into account the phenotypes already described in the literature, i.e., ESADA, Icelandic Sleep Cohort, and BAVENO classification; 3. implementation of an "Italian database" for long-term follow-up studies. The project will set an HUB and SPOKE organization that include 4 leading research Sleep Center distributed over the Italian territory in collaboration with the Italian Scientific Society of Sleep Medicine (AIMS) network. AIMS is member of the European Federation of National Sleep Society as well as part of World Sleep Association. Methods - Clinical, sleep study and treatment data will be collected for each patient. A clinical questionnaire will be developed in order to standardize the clinical data collection; to this end a feasibility study will be performed on 100 patients (25 pts for Coordinator/HUB center). Additional clinical tests will include: EKG, Spirometry, ABPM, standard blood chemistry, CPR, TSH reflex, glycemic control assesment, Vitamin D and B12. - Excessive daytime Sleepiness, Neurocognitive, anxiety/depression screening will be performed by means of ESS, MOCA and HADS, respectively - A web-based data collection platform will be designed to store pseudo-anonymized individual data. OUTCOMES 1. Distribution of OSA severity in Italy according to the different classification methods (AHI based; hypoxic burden; Icelandic Sleep Cohort, ESADA and BAVENO method) 2. Definition of metabolic, cerebro- and cardiovascular risk factors prevalence associated with OSA in Italian Population 3. Distribution of different physiological and clinical patterns and their association with co-morbidities; analysis of differences with other populations. 4. Definition of a screening/case finding questionnaire for Italian Population 5. Definition of an ongoing cohort of patients that will be followed-up 6. Implementation of an OSA registry that will be shared with Italian Health System or Agencies to designed preventive or early diagnosis interventions to reduce the health impact of the disease.

Rescue Stenting and Intravenous Thrombolysis in Patients with Large Vessel Ischemic Stroke

A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)

Mouthpiece With Integrated Cheek Support vs. Manual Cheek Support During Respiratory Oscillometry

Study design: prospective, randomized, cross-over study. Study population: Subjects who will present themselves at the participating doctors' offices. Inclusion criteria: subjects aged between 5 and 75 years. Exclusion criteria: Subjects unable to follow the study procedures or with any physical or mental condition deemed unsuitable by the doctor will be excluded from the study. Study protocol: the measurement protocol will consist of measuring the subject's facial morphological parameters and respiratory impedance parameters, followed by the administration of a questionnaire on perceived comfort. The procedure will be performed in a seated position. Measurements: 1. Morphological Parameters Using a sliding caliper. The following anatomical distances will be measured on the seated subject, looking straight ahead with teeth together, facial muscles relaxed, and mouth closed: a) BIGONIAL WIDTH: The straight-line distance between the right and left angles of the mandible; b) LIP LENGTH: The straight-line distance between the right and left corners of the closed mouth." 2. Respiratory Impedance. The impedance measurement will be performed using the Resmon FIRST (Restech srl, Milan, Italy). Repeated measurements will be taken for each subject three times (TRIPLICATE) over 10 breaths with mono-frequency oscillations at 5 Hz. The enrolled subjects will perform the following measurements in a random order: - One TRIPLICATE session of respiratory impedance with cheeks supported by study personnel. - One TRIPLICATE session of respiratory impedance with cheeks supported by the cheek support. The study personnel will record any operator errors associated with preparing and using the cheek support on the enrolled participants. 3. Comfort Evaluation Questionnaire. At the end of the measurements, each participant will be asked to complete a comfort evaluation questionnaire regarding their experience during the procedure. Currently, no commercial devices are similar to the cheek support being tested. Therefore, the questionnaire is a modified version of a questionnaire previously used to evaluate the comfort of mechanical respirators worn on patients' faces during the coronavirus disease (COVID-19) period (Respirator Comfort, Wearing Experience, and Function Instrument (R-COMFI)3). The questionnaire aims to cover sensations of discomfort and general impressions of using the mouthpiece with cheek support during respiratory oscillometry measurements. Sample size: The total number of subjects to be enrolled in the study is 55. This number was determined based on the following assumptions: - Type-I error (α) = 5%, study power (1-β) >= 80% - Uniform distribution of subjects in the following age groups: 6-17, 18-75 years - Range of Resistance (Rrs) = 2...15 cmH2O/(L/s) - Range of Reactance (Xrs) = 0...-14 cmH2O/(L/s) - Minimum expected differences: the investigators set the minimum expected difference at 10% with a minimum value of 0.1 cmH2O/(L/s) (see table below) - Expected standard deviation of variation: the investigators assume the expected standard deviation of variation to be the standard deviation of the short-term repeatability of oscillometry measurements reported in the literature (see table below) - Dropout rate = 10% Data analysis: 1. Comparison between the Cheek Holder Mouthpiece and Operator Support. The differences between the measurements taken with manual cheek support and those taken with the cheek holder will be analyzed. The two methods will be considered equivalent if the mean difference between the results and the 95% confidence interval of the Deming regression fall within the expected short-term variability of the technique for the tested population. Specifically: - For Rrs, a difference within 17% in adults and 27% in children, with a minimum acceptable difference of 1 cmH2O/(L/s), will be considered acceptable. - For Xrs, a difference within 37% in adults and 40% in children, with a minimum acceptable difference of 0.5 cmH2O/(L/s), will be considered acceptable. 2. Evaluation of Patient Comfort. The comfort of each patient will be assessed using a scoring system associated with specific questions. The total scores obtained with the two methodologies will be compared using a paired t-test or alternative tests for non-parametric distributions. 3. Evaluation of the Impact of Face Dimensions on FOT Test Accuracy. The impact of face dimensions on the effectiveness of the cheek holder support will be assessed by investigating the presence of a correlation between the differences in results obtained with the cheek holder and those obtained with manual support by the physician relative to lip length (LIP) and bigonial width. The type and frequency of user errors will be summarized for the entire population and for each age group using descriptive statistics (mean and standard deviation or median and ranges, as appropriate).

SCAD : a Registry of Spontaneous Coronary Artery Dissection

Observational, multicentre, international retrospective and prospective cohort study. Since this is an observational study, a formal sample size is not necessary. At least 500 prospectively recruited patients and 500 historical cases will be enrolled. Patient data will be collected at the following time-points: - First SCAD event visit (retrospectively on chart review) - First follow-up: at time of enrolment - Yearly follow-up: up to 1, 2, 3, 4 and 5 years post enrolment or until study completion Approximately 30 countries and 120 sites will participate in this registry.

Phase 4 Paediatric Study to Evaluate Sonazoid Safety and Efficacy for Contrast-Enhanced Ultrasound Liver Imaging

This Phase 4, open-label, non-randomised, multicentre prospective study in Europe will enrol paediatric patients who are presenting with ≥1 confirmed untreated target FLL. This study plans to enrol at least 50 subjects at up to 12 centres in Europe. If a patient has multiple FLLs, the Investigator must select the target lesion at their discretion. Where possible, the target lesion should be a clearly visible and accessible lesion that could be easily followed during the non-CE ultrasound examination and all phases of the CEUS examination. The reference diagnosis/standard of truth for the target lesion of interest will be established by the principal investigators/sub-investigators on the basis of all available clinical information, including the results of biopsy, if available, and the dynamic CECT or CEMRI examination required for the study. Following unenhanced (pre-contrast) ultrasound imaging of the target FLL, a single dose of Sonazoid™, dosed according to body weight (0.12 μL microbubbles/kg), will be intravenously administered to each patient, and a CEUS examination will be performed, with images acquired as specified in the Imaging Manual. The unenhanced ultrasound and CEUS images will be assessed by 3 independent blinded readers following WFUMB-EFSUMB guidelines for adults, and in accordance with the Independent Review Charter. The diagnoses based on the unenhanced ultrasound and the CEUS results will be compared with the reference diagnosis/standard of truth for the target lesion. The diagnostic accuracy, sensitivity and specificity of the unenhanced ultrasound and CEUS images will then be calculated. Clinical safety data will be collected throughout the study. Safety will be evaluated by monitoring subjects for the occurrence of AEs.

Efficacy Of Upadacitinib In Psoriatic Arthritis And Comparison To Rheumatoid Arthritis.

This is a multicentric prospective observational study in which consecutive patients diagnosed with Psoriatic Arthritis (any subset) and Rheumatoid Arthritis, that according to clinicians' evaluation should be treated with Upadacitinib therapy, will be recruited from the outpatient clinic of the Rheumatology Department of the centers included in the study. The investigators will enroll consecutive patients with Psoriatic Arthritis and Rheumatoid Arthritis with active disease and fulfilling the inclusion and exclusion criteria, from the outpatient clinic of the Rheumatology Units of the participating centers. Written informed consent will be obtained prior to the beginning of the study. All patients, in line with clinical routine practice, will undergo a standard clinical, laboratory, and imaging assessment in order to define the disease activity according to standardized disease activity indexes, at baseline and during the first 3 follow-up visits. For patients starting new treatments for Psoriatic Arthritis and Rheumatoid Arthritis, the follow-up visits are generally scheduled after 1 month (± 1 week), 3 months (± 2 weeks), and 6 months (± 4 weeks) post-treatment initiation, in accordance with international guidelines and local protocols. In case of suspicion of axial involvement, an MRI of the sacroiliac joints will be performed at baseline and, in case of positivity, will be repeated after 6 months (±1 month) in order to assess disease activity at the spine and the treatment efficacy. Regarding the Patient Reported Outcome, the investigators will assess these during the scheduled visits, and two weeks after the initiation of treatment to evaluate earlier pain and functional improvement. The Patient Reported Outcome assessment at two weeks will be administered in a paper form to participants during the baseline visit, and subsequently participants will return these during the first follow-up visit. The data for the study will be retrieved from the medical records of participants and recorded into an appositely created electronic case report form.

A Clinical Trial Evaluating the Safety and Efficacy of a New Light Combination Therapy Addressing Intermediate AMD

*Objectives* 1. The primary objective is to evaluate the safety of the reSEES treatment. 2. The secondary objective is to evaluate the effect of the reSEES treatment on the progression of intermediate AMD. - Progression of intermediate AMD will be followed for one year, - The contralateral eye will be used as a control to compare and observe relative and absolute progression and rate of progression. *Other objectives* - Evaluate the evolution of AMD-induced retinal morphological changes. - Evaluate changes at the choriocapillaris vascular network and analyse/compare eventual transition to nAMD with natural history. - Evaluate the effect of reSEES on retina functional parameters. - Investigate the effect of reSEES on patients' perceived vision, mood, and general well-being. - Evaluate the usability of the proposed laser console. *Study Details* 30 patients are planned to be included in the study Enrolled patients will receive treatment on the left or the worst eye, and the fellow eye will be used as a control. Enrolled patients must have both eyes eligible for the study (rf. Inclusion Criteria) *Measurements & Procedures* The measurements and procedures will be performed within 52 weeks. - Total number of visits: 10 - Total number of treatments: 9 General health, medical history, and concomitant medication will be assessed and reported. Ophthalmic examinations will be carried out at different time points: at screening, on Days 3, 10, and 17, and at the follow-up visits at 18, 24, and 52 weeks from T0 Adverse events and occurring changes in concomitant medication will also be collected for evaluation at every time point.