Dwārka, India

Neurosurgical Outcome Network

The evaluation of outcome indicators, quality of life, and complexity in Neurosurgery has gained significant importance not only at a clinical and therapeutic level but also as a tool to assess the effectiveness and efficiency of the healthcare system. This study aims to evaluate neurosurgical outcomes and their predictors using measures shared among participating centers. Such evaluation varies from center to center, and the predictive factors are not entirely known or shared. Standardizing the evaluation of outcomes and predictors improves research quality, enables data comparison, and fosters a common language in everyday clinical practice. Most importantly, it influences therapeutic decisions in various neurosurgical pathologies. Primary Objective: Collect and describe the pre- and postoperative clinical, cognitive, and psychological status in various neurosurgical pathologies. Secondary Objectives: Identify outcome predictors. Primary Endpoint: Description of pre- and postoperative clinical, cognitive, and psychological data of patients undergoing neurosurgical intervention. Secondary Endpoints: Analyze the association between preoperative indicators collected and postoperative outcomes. Specific predictors and outcome measures for each neurosurgical pathology will be considered and reported in Appendix 1. Patient enrollment from Neurosurgery Departments; collection of clinical, cognitive, and psychological data before the intervention and during follow-up after the intervention (timing varies depending on the neurosurgical pathology); data analysis through AI. For all neurosurgical pathologies, the following data will be collected: sociodemographic, clinical (Charlson Comorbidity Index, heart disease, diabetes, Chronic Obstructive Pulmonary Disease, hypertension, Body Mass Index, smoking, psychiatric pathology, admission date, intervention date, discharge date, Modified Rankin Scale, American Society of Anesthesiologists, weight, height), anesthesiological (collected only by FINCB), and complication-related data (Novel Therapy-Disability-Neurology).

ConTempoRary Cardiac Stimulation in Clinical practicE: lEft, BivEntriculAr, Right, and conDuction System Pacing

Cardiac pacing with implantable electronic cardiac devices and transvenous leads has been introduced since 1960 and is considered a safe, effective and low-risk therapy. The most common indications for permanent cardiac pacing are sinus node dysfunction and atrioventricular blocks. In Europe, pacemaker implants exceed 1000 per million inhabitants. The aim of this therapy is not only to improve patients survival but also their quality of life, which is an essential aspect in assessing patients clinical status and prognosis. Nowadays, five types of cardiac pacing are recognised in clinical practice: - Endocardial right chambers pacing: the device is implanted in the subcutaneous subclavian area and it is connected to transvenous leads implanted in the right cardiac chambers, which detect intrinsic electrical activity and stimulate when needed; - Epicardial pacing: this procedure is often performed in conjunction with cardiac surgery; - Cardiac resynchronisation therapy (CRT): it delivers biventricular or left ventricular pacing in order to correct interventricular electromechanical dyssynchrony and to improve cardiac output; - Conduction system pacing: it stimulates the His bundle or the left bundle branch area downstream of the conduction block, in order to restore a physiological electromechanical activation. - Leadless pacing: via a percutaneous approach through a large-calibre vein, leadless device is placed inside the right ventricle. These pacing modalities have different possibilities to restore a normal cardiac electromechanical activation, resulting in different degrees of mechanical efficiency in terms of systolic output and diastolic pressures, with consequent effects on improvement/onset of heart failure and cardiopulmonary performance of our patients. Right ventricular pacing induces a dyssynchronous cardiac activation pattern that can lead to left systolic dysfunction and a consequent increased risk of death related to the development of heart failure. These observations led to the study of alternative cardiac pacing modalities since the 1990s, in order to improve the clinical outcome of patients with symptomatic bradyarrhythmias. The study of pathological ventricular activation due to left bundle-branch block represents the pathophysiological premise of cardiac resynchronisation in patients with systolic dysfunctional heart failure, and constitutes the developmental model for physiological pacing. CRT improves mortality and quality of life in patients with heart failure and reduced left ventricular ejection fraction. Typically left ventricular pacing is achieved by placing a catheter in the posterolateral area through a venous branch of the coronary sinus. Unfortunately, despite several years of experience in this field, clinical non-response to this therapy is observed in between 20% and 40% of patients, mostly due to the inability to reach the appropriate pacing site because of anatomical difficulties/absence of veins in the target area. Recently, conduction system pacing (CSP) has rapidly emerged as an alternative pacing modality to both right ventricular pacing (RVP) and CRT, in order to achieve a more physiological pacing. His bundle pacing (HBP) is considered the physiological pacing "par excellence", but the results in literature show rather frequent technical difficulties due to high pacing thresholds, inadequate ventricular signal amplitude for the detection of intrinsic cardiac activity, low success rate and risk of progression of conduction system pathology in patients with infranodal conduction defects. Left bundle area pacing has more recently emerged as a viable alternative to achieve physiological pacing with haemodynamic parameters similar to those of HBP, but with lower and stable pacing thresholds, ventricular signal amplitude adequate for the detection of intrinsic cardiac activity and high success rate. Several experiences with different pacing systems have been published, mainly single-centre studies with small sample sizes and different definitions of conduction system pacing success. In non-randomised comparative studies, and thus with methodological limitations, clinical superiority over conventional right ventricular pacing, and a substantial efficacy equivalent to CRT in patients with left bundle-branch block, has been shown, creating the preconditions for widespread use of the CSP. Considering, therefore, the widespread use of the latter technique and the high rate of implants that can potentially benefit from physiological pacing, evaluating safety, feasibility, timing and benefits becomes more crucial than ever. Therefore, the goal of this observational study is to evaluate the clinical characteristics of patients undergoing permanent cardiac pacing and to compare procedural efficacy and safety of different implantation approaches in the clinical practice of the participating centres. The contribution of non-fluoroscopic anatomical and electrophysiological reconstruction systems to device implantation procedures will also be evaluated. The investigators will collect clinical and procedural data from patients with an indication for permanent cardiac pacing who have consecutively undergone an implantable electronic device implant procedure at the Electrophysiology Laboratories of the participating centres over a period of 120 months from the time of approval with a follow-up of an equal 120 months. Patients will be classified according to the type of stimulation: 1. Right chambers endocardial pacing; 2. Cardiac resynchronisation therapy; 3. Conduction system pacing: 1. His bundle pacing 2. Left bundle branch area pacing. In addition, the efficacy and safety at 30 days, and the efficacy and safety at 6 and 12 months of the various pacing modalities, will be evaluated. The investigators defined efficacy at 30 days the presence of stable electrical parameters - or, if unstable, not requiring early re-intervention, the absence of cardiovascular hospitalizations and the absence of cardiovascular death. The investigators defined safety at 30 days the absence of procedural complications, such as haematoma requiring re-intervention or with haemoglobin loss >2gr/dl, pneumothorax, pericardial effusion requiring drainage, lead dislocation, cardiac implantable electronic device (CIED) infection or a re-intervention for any cause. Equally, the investigators defined efficacy at 6-12 months the presence of stable electrical parameters - or, if unstable, not requiring re-intervention, the absence of cardiovascular hospitalizations, the absence of cardiovascular death, the occurrence of heart failure, the occurrence or worsening of atrial or ventricular tachyarrhythmias. Therefore, the investigators defined safety at 6-12 months the proper functioning of the device, the absence of infection and the absence of re-intervention for any cause.

Regorafenib for Recurrent Grade 2 and 3 Meningioma (MIRAGE Trial)

Initiation of Continuous Glucose Monitoring in Adults With Type 2 Diabetes Treated With Basal Insulin, in Italy

This is a post-market, multi-centre, prospective, interventional single arm study in Italy. Participants will use the FreeStyle Libre 2 Flash Glucose Monitoring System, according to the labelling, to monitor their glucose for approximately 3 months. Additional therapies may be introduced, if clinically indicated, based on review of the participant's clinical data and in line with national guidance. HbA1c will be tested at the start and end of the study for primary endpoint analysis.

Incidence of Severe COVID-19 Infection in Patients With CLL or B-NHL Who Received Pre-exposure Prophylaxis With Tixagevimab and Cilgavimab in Italy.

This is an observational retrospective and prospective multicenter study aimed at describing the role of the COVID -19 prophylaxis with Tixagevimab and Cilgavimab in CLL or indolent B-NHL patients. All CLL or indolent B-cell NHL patients (follicular lymphoma, marginal zone lymphoma, lymphoplasmacytic lymphoma) who received first COVID-19 prophylaxis dose with Tixagevimab and Cilgavimab according to AIFA indication between March 2022 and October 2022 will be included in the study. Each patient will be followed for a maximum of 12 months from the first COVID-19 prophylaxis dose.

A Prospective, Observational Cohort Study on the Clinical Impact of Novel Monoclonal Antibodies in B-cell Non-Hodgkin Lymphoma in Italian Clinical Practice

This is a large prospective, observational cohort study aimed at collecting clinical information on use, feasibility, short- and long-term efficacy and short- and long-term toxicity of novel MAB that have received approval from EMA since 2020 and are prescribed according to the indications for use authorized for marketing in Italy. Patients entering the study will be subdivided into different cohorts based on approved treatment indications, type of antibody employed and histological subtype. Additional sub-cohorts will be defined if needed. Final outputs will be based according to: - Per indication analysis; - Pooled analyses by type of antibody and subtype and other parameters; - A general analysis of the whole cohort.

A Study to Investigate Safety and Tolerability of TransCon IL-2 β/γ Alone or in Combination With Pembrolizumab and/or TransCon TLR7/8 Agonist or Other Anticancer Therapies in Adult Participants With Locally Advanced or Metastatic Solid Tumor Malignancies

IL-2 is a key cytokine that directs the immune system through pleiotropic effects mediated by promoting expansion of both cytotoxic effector cells and Tregs. TransCon IL-2 β/γ is designed as a long-acting delivery prodrug of IL-2 β/γ, a potent cytokine signaling molecule, with the potential to improve the safety and efficacy of IL-2.

Shortened vs Standard Chemotherapy Combined With Immunotherapy for the Initial Treatment of Patients With High Tumor Burden Follicular Lymphoma

This is an open-label, multicenter, randomized phase III trial. The study plans to randomize patients with a 1:1 ratio to Arm A (Standard arm) or Arm B (Experimental arm). Once randomized, each patient will start immunochemotherapy with one of the approved regimens (R-CHOP, R-Bendamustine, G-CHOP, G-Bendamustine, G-CVP) chosen by the physician on a patient basis before randomization. Patients randomized to Arm A will receive an induction immunochemotherapy at full doses (standard schedule). After cycle 4, patients will be assessed for response and will complete their planned therapy if at least a stable disease is confirmed. Patients randomized to Arm B will start their induction treatment with 4 cycles of the immunochemotherapy standard dose chosen by the physician: after cycle 4, patients will be assessed for response and will proceed with subsequent treatment based on the quality of their response. Specifically: - Patients achieving a Complete Remission (CR) will receive a shortened treatment: in detail, they won't receive any further chemotherapy but will complete induction with 4 additional cycles of only the Monoclonal Antibody (MoAb) given during the first four cycles (in case of G-bendamustine, 2 additional cycles of obinutuzumab); - In case if response less than Complete Remission (CR), Partial Remission (PR) or Stable Disease (SD), patients will complete treatment as planned for patients in Arm A. In both arms, at the end of induction responding patients (CR, PR) will be addressed to a standard anti-CD20 maintenance (1 dose every 8 weeks for two years) with the same Monoclonal Antibody (MoAb) given during induction. Patients with progressive disease at any time (regardless of treatment arm) will be addressed to salvage therapy. The study plans the evaluation of quality of life by collecting the Patient-Reported Outcome(s) (PROs) through the Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym questionnaire) at predetermined timepoints during the study.

Exploiting Circulating Tumour DNA to Intensify the Postoperative Treatment Resected Colon Cancer Patients

This is a prospective, open-label, multicentre study, including two phase II randomized trials. In Part 1 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after surgery will be randomized to receive FOLFOX for 12 cycles or CAPOX for 8 cycles (at investigator choice) versus FOLFOXIRI for 12 cycles. In Part 1 target-driven resected stage III and high-risk stage II HER2+ and RAS wild-type colon cancer patients with positive ct-DNA after surgery will receive Trastuzumab and Tucatinib plus FOLFOX for 12 cycles. In Part 2 resected stage III and high-risk stage II colon cancer patients with positive ct- DNA after the end of a fluoropyrimidine and oxaliplatin-based adjuvant therapy - either in the frame or outside of Part 1 - will be randomized to receive observation or Trifluridine/Tipiracil for 6 cycles.

Retrospective Study of 2nd-line Therapies After CDK4/6i + Hormonal Therapy in HR+/HER2- Advanced Breast Cancer

Multicenter retrospective observational study, describing therapeutic choices as second-line treatment in patients with HR + / HER2- advanced breast cancer in a real world setting, in centers adhering to the Hermione Network. The study involves the analysis of patients with HR + / HER2- advanced breast cancer treated in second line after initial treatment failure with aromatase inhibitor or Fulvestrant + CDK4 / 6i (Palbociclib, Ribociclib or Abemaciclib). Data will be collected from 150 patients with at least one radiological re-evaluation of disease during 2nd-line treatment from 01 January 2016 until 31 December 2020. List of collected information: Patients' characteristics (gender, age at diagnosis, menopausal state); Disease definition at diagnosis (stage, tumour histology, hormonal status); Surgery (date of surgery, type of surgical approach); Neo-adjuvant treatment; Adjuvant treatment; Date of first relapse (and time since the end of adjuvant therapy); Locations of metastases, Biopsy of metastases, Hormonal receptor status; First-line treatment, hormonal therapy, Best response, Cause of treatment end; Second-line treatment, Best response (radiological re-evaluation), Toxicity, Cause of treatment end. Demographics, baseline characteristics (including tumor characteristics) and treatment information will be summarized descriptively. The categorical variables will be presented in the form of frequencies and percentages, while the continuous variables will be presented by mean, standard deviation and minimum and maximum values. A logistic model will be used for the analysis of clinical benefit (categorical variable), while for the analysis of time-to-event indicators a proportional hazard model will be used. For both analyses, the optimal model will be chosen with the method of "backward" selection. A threshold value of 5% will be used to include predictive variables in the model. The estimates derived by the final models will be evaluated using a penalized model for the evaluation of maximal probability, according to the Firth approach.