Driebergen-rijsenburg, Netherlands

Multimodal Prehabilitation in Cancer Surgery

The standard treatment for most solid cancer includes surgery and concurrent medical therapies, both of which have been shown to significantly improve prognosis. However, cancer treatments impose impactful physiological stress and have detrimental effects on acute and long-term health outcomes. Physical, nutritional, and mental status can influence surgical outcomes, functional recovery and quality of life throughout the course of the disease. The importance of postoperative rehabilitation on physical performance and recovery is well-recognized. However, the preoperative period provides a unique opportunity to address comorbidities and modifiable risk factors. In addition, the metabolic stress induced by neoadjuvant therapy has been documented to frequently result in muscle atrophy and diminished functional capacity. The recognition that selected risk factors of poor postoperative outcome can be modified has prompted clinicians to identify proactive interventions to facilitate the recovery process. In this context, prehabilitation, aimed at enhancing the patients' functional capacity to enable them to withstand the physiological stress of surgery, has emerged as a promising approach. Although the term prehabilitation is not novel, the concept of optimizing patients before acute stressor or treatment has gained attention over the last decade. Nonetheless, quantifiable evidence of its effectiveness has yet to be fully demonstrated. This study is a multicenter randomized controlled trial to assess the efficacy of personalized procedure-specific prehabilitation programs on patient-centered surgical outcomes. A total of 400 patients will be recruited by systematic screening of patients scheduled for elective surgical procedures. All patients undergoing elective major abdominal (including urological), thoracic (including breast) or gynecological cancer surgery undergoing major cancer surgery will be screened for eligibility and those who meet the inclusion/exclusion criteria will be approached for consent. Research personnel will use a web-based randomization system to assign patients (1:1 ratio) to either the prehabilitation or control arm. Study personnel will also collect data on recruitment rates, with reasons for non-enrolment. Eligible patients will be randomly assigned to 1 of 2 treatments: 1. multimodal prehabilitation program for at least three weeks started as soon as possible before surgery; 2. standard care. The multimodal prehabilitation program will be individualized by carefully integrating and adapting various components to meet individual needs. The program will last at least three weeks (plus maintenance in case of delayed surgery), and will incorporate exercise training, nutritional therapy, and anxiety reduction techniques. After enrollment, patients will receive initial contact from trained personnel through telemedicine. To ensure personalized care, a comprehensive assessment will be conducted to identify specific physical, nutritional, or psychological challenges. Based on this assessment, a customized intervention plan will be prescribed to achieve tailored exercise training, optimized nutrition, and effective distress-coping strategies. All patients will be reassessed the day before surgery and 30 days after surgery. Based on the data obtained during the multimodal assessment, different domains and levels of care will be prescribed, focusing on exercise training, nutrition optimization, or distress-coping techniques-or a combination of these

Advancing Knowledge in Ischemic Stroke Patients on Oral Anticoagulants

MiniLap Vs Standard Laparoscopy in Prophylactic Bilateral Salpingo-oophorectomy in BRCA-Mutated Patients

Italian Anderson Fabry Disease Cardiovascular Registry

1. Introduction Anderson-Fabry Disease (AFD) is a multisystemic lysosomal storage disorder with X-linked inheritance (Online Mendelian Inheritance in Man [OMIM] number 301500) caused by a total or partial deficiency of the enzyme α-galactosidase A (α-Gal A), encoded by the GLA gene (Xq22.1). The deficiency of α-Gal A leads to the accumulation of neutral glycosphingolipids, particularly globotriaosylceramide (Gb3) and galactosylceramide, in various cell types and tissues. The continuous accumulation of these molecules results in progressive cellular dysfunction, triggering inflammatory and pro-fibrotic phenomena that cause organ dysfunction. The clinical manifestations and age of onset of the disease are highly variable, and symptoms/signs often appear only after a degree of irreversible damage has already occurred. The classic form of AFD is the most severe clinical phenotype and predominantly affects males with null or minimal residual enzymatic activity (<1% of normal values). Symptoms begin early during childhood or adolescence and include acroparesthesias, angiokeratomas, telangiectasias, gastrointestinal disturbances, corneal alterations (cornea verticillata), proteinuria, renal insufficiency, hypo/hyperhidrosis, and hearing loss. Later in adulthood, progressive cardiac and cerebrovascular involvement may occur. Patients with atypical or late-onset variants generally develop the disease later (from the third to the seventh decade of life) compared to those with the classic form. The clinical picture is generally dominated by the involvement of a single organ, most frequently the heart. The measurement of residual enzymatic activity of α-Gal A is sufficient to establish a diagnosis in males. However, it is important to identify the specific genetic mutation to determine the disease phenotype and exclude benign polymorphisms that may cause reduced enzymatic activity levels. In females, genetic diagnosis is indispensable, as residual enzymatic activity often falls within the normal range. The treatment of AFD is based on compensating for the deficient enzymatic activity through enzyme replacement therapy (ERT) and managing the disease's symptoms and complications. More recently, an oral chaperone therapy capable of increasing residual enzymatic activity has been approved, though it is only effective for certain mutation types. Given the multisystemic involvement in AFD patients, longitudinal multispecialty evaluation is necessary, including cardiology, nephrology, neurology, dermatology, ophthalmology, and otorhinolaryngology assessments. Cardiac involvement is the main prognostic factor, with cardiovascular death being the leading cause of mortality. Manifestations include unexplained ventricular hypertrophy (which must be differentiated from the more common sarcomeric hypertrophic cardiomyopathy), valvular diseases, angina pectoris due to coronary microcirculation dysfunction, conduction abnormalities (which may require permanent pacemaker implantation), and supraventricular and ventricular tachyarrhythmias. Cardiological evaluation is recommended annually or earlier if clinically indicated, including systemic blood pressure assessment, ECG, echocardiography, and arrhythmia detection via 24-hour Holter ECG monitoring (or extended monitoring [e.g., loop recorder] when deemed appropriate). In recent years, cardiac magnetic resonance imaging (CMR) has become a key investigation not only for diagnosing the disease but also for its follow-up and for evaluating the response to therapy. CMR allows for accurate assessment of cardiac chamber volumes and function and enables tissue characterization using gadolinium-based contrast agents and advanced T1 and T2 mapping techniques. Endomyocardial biopsy is now reserved for patients with genetic variants of uncertain significance (VUS), high residual enzymatic activity (>10%), and/or low lyso-Gb3 levels to confirm or exclude AFD as the cause of left ventricular hypertrophy. 2. Study Background AFD is a rare disease, and the estimated prevalence of the classic forms was previously reported to range between 1:40,000 and 1:117,000. However, these data likely represent an underestimation, as the manifestations are nonspecific, and AFD is often not considered among diagnostic hypotheses, leading to misdiagnosis or delayed diagnosis. Supporting this, recent genetic newborn screening programs not based on symptom development suggest that AFD may be far more common than previously suspected. Although the last decade has seen increasing understanding of the disease's pathophysiological mechanisms, natural history, and the efficacy and limitations of current therapeutic options, many unanswered questions remain. This highlights the need to create an Italian cardiological registry for Anderson-Fabry Disease to bring together various centers located in different regions nationwide to collect the largest possible number of patients. 3. Study Objectives - Evaluate the clinical profile, prevalence, and incidence of the disease (relative to the general population), as well as the family and natural history of AFD patients, particularly the incidence of morbidity/mortality during follow-up. - Identify clinical and instrumental predictors of cardiovascular morbidity and mortality to improve risk stratification and personalize the most appropriate management program for each patient. - Assess the correlation between genetic findings, phenotype, and prognosis, with particular emphasis on differences in cardiac involvement between classic and late-onset variants with cardiac involvement. - Investigate serological/tissue markers and instrumental indicators of early organ damage. 4. Study Plan 4.1 Study Population All patients affected by Anderson-Fabry Disease (AFD), diagnosed according to current international guidelines, will be included in the study upon obtaining informed consent. Based on the estimated prevalence of the disease, the study plans to enroll approximately 800 patients over 10 years. Inclusion Criteria: - Patients diagnosed with Anderson-Fabry Disease. - Age ≥ 2 years at the time of diagnosis. - Informed consent obtained from the patient or their parent/legal guardian. Exclusion Criteria: - None. 4.2 Study Design The study is an Italian multicenter, observational, retrospective, and prospective, non-pharmacological study. Participation will be proposed consecutively to all patients with AFD attending the participating centers, both as outpatients and inpatients. Structured data collection for objective evaluation will occur through a dedicated electronic archive, gathering data from the observation period between January 1, 1981, and December 31, 2031. This electronic archive may be used to obtain or confirm new scientific evidence regarding AFD, particularly focusing on diagnosis, prognosis, and therapy. Data entry into the electronic archive will be based on the review of medical records (outpatient or inpatient), collecting information about demographics, past and recent medical history, family history, genetic investigations, instrumental assessments, signs and symptoms of the disease, and therapy. Data Collection Modes: - Prospective Phase: Patients will be enrolled during hospitalization or at the first outpatient visit after obtaining free and informed consent. Patients will subsequently undergo clinical evaluations, instrumental investigations, and therapeutic interventions as per clinical necessity and standard care practices. A minimum follow-up duration is not required; even a single evaluation suffices for inclusion in the archive. - Retrospective Phase: Data from patients will be retrospectively collected starting from January 1, 1981. In this phase, no predefined observation period is required. If the patient is no longer being followed, a substitute declaration of consent for retrospective observational studies will be used to utilize clinical/instrumental data excluding genetic data. In all cases where it is possible to provide adequate information, particularly when patients return to care centers for health services or follow-up visits, their consent for data processing must be obtained. 4.3 Discontinuation of Participation Patients may choose to discontinue their participation in the study at any time. 4.4 Visits and Assessments Specialist visits, laboratory tests, genetic analyses, and instrumental evaluations to which patients are or will be subjected fall within the normal care pathway, in line with the standard of care. The data collected will derive from initial and follow-up visits or hospitalizations that are part of standard clinical practice. 5. Data Management and Statistical Analysis 5.1 Data Collection Methods Systematic data collection will occur through the creation of a dedicated electronic archive, collecting data for the observation period between January 1, 1981, and December 31, 2031. Clinical data required by the protocol will be pseudonymized and entered by designated staff into an electronic Case Report Form (eCRF) managed via the REDCap platform. The eCRF in REDCap will be developed and managed following the procedure outlined in the "Operational Instruction for the Management and Use of the REDCap Platform" (IOA119). The Principal Investigator must specify the personnel delegated for data management and their respective roles in the study in the Delegation Log. Collected data will be derived from standard care medical records, with no study-specific assessments performed. 5.2 Statistical Methods The collected data will include demographics (age, gender), medical history, instrumental data (ECG, echocardiography, cardiac MRI, stress tests, 24-hour Holter ECG, biopsies), laboratory data (CBC, platelets, renal and liver function, BNP, troponin, serum electrolytes, urinalysis, etc.), genetic investigation findings, and follow-up data. The results of the analysis will be processed statistically in anonymous form to derive the study objectives. Data will be presented using descriptive statistics: - Qualitative parameters will be expressed as numbers or percentages and analyzed using Chi-square or Fisher's exact test. - Quantitative parameters will be expressed as mean and standard deviation or as median and interquartile range, with comparisons between patients performed using parametric tests (ANOVA, Student's t-test) or non-parametric tests (Kruskal-Wallis and Mann-Whitney U tests). A p-value ≤ 0.05 will be considered statistically significant. Statistical analyses will be conducted using Stata/SE v.14.2 for Windows. 6. Administrative Procedures Good Clinical Practice Guidelines This study will be conducted in compliance with Good Clinical Practice (GCP) guidelines [ICH Harmonized Tripartite Guidelines for GCP 1996 Directive 91/507/EEC; D.M. 15.7.1997], the Declaration of Helsinki, and national regulations governing clinical research. By signing the protocol, the investigator agrees to adhere to the procedures and instructions contained therein and to conduct the study according to GCP, the Declaration of Helsinki, and national regulations on clinical trials. Protocol Amendments or Study Modifications Any protocol modifications will be implemented as formal amendments. No protocol modifications are allowed during the study period. Any unforeseen changes in study conduct will be documented in the "Clinical Study Report." Ethical Committee Approval The study protocol, any amendments, informed consent forms, and patient information must be approved by the Ethics Committee. For amendments, the Investigator may immediately implement changes to ensure patient safety and must notify the Ethics Committee within 10 working days. Consent Management Patients will be enrolled during hospitalization or outpatient visits, and each participant must sign an informed consent form. - For the prospective phase, consent will be obtained during the standard diagnostic process. - For the retrospective phase, concerning previously collected data, informed consent will be sought during follow-up visits. For deceased or unreachable patients, data will be processed without consent based on General Authorization No. 146/2019 from the Privacy Authority, excluding genetic data. Documentation Archive. The Investigator is responsible for archiving and storing essential study documents before, during, and after the study in compliance with applicable regulations and GCP. Data in the CRF will be strictly anonymous, and subjects will be identified only by a number and initials. Publication of Results Data publication will occur after processing during the data collection period or after the final update of the archive. Costs No additional costs are foreseen for conducting this study. Clinical evaluations and instrumental examinations are routinely performed in these patients as part of standard clinical practice.

Study on Post-acute Myocardial Infarction Ventricular Defect: Outcome Evalutation in Relation to Surgical Timing

Identify the optimal timing for the treatment of post-infarction ventricular defect, considering the time interval between the clinical-instrumental diagnosis and the surgical intervention.

A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy

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).

Development of an Artificial Intelligence Model for Optimising Therapy in Gliomas Gliomas

Artificial intelligence (AI) undoubtedly represents the main tool currently available in the definition of complex algorithms and its use in the medical field is becoming increasingly strategic.As reported in the literature, it is increasingly difficult to find new therapeutic strategies for neoplasms, especially neurological ones. Molecular characterisation is therefore increasingly essential, as is the use of new predictive methods. With this in mind, the aim of this study is to assess, by means of AI algorithms applied to genomic data, in what percentage molecular alterations are susceptible to potential drug therapies, compared to the literature data that does not consider AI algorithms for this purpose.

Atezolizumab and Rechallenge Chemotherapy in Relapsed Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC).

The CARRY-ON study is a multicenter, prospective, open-label single-arm phase II trial, designed to seek for a signal of efficacy of continuing PD-L1 inhibition in patients with sensitive relapse ES-SCLC by adding atezolizumab to rechallenge carboplatin-etoposide chemotherapy. The trial is planned to enroll 142 patients with sensitive relapse ES-SCLC from 25 Italian centers. Sensitive relapse is defined as SCLC relapsed or progressed to first-line chemo-immunotherapy with PD-L1 inhibition (with either atezolizumab or durvalumab) at least 60 days after the last chemotherapy administration. Eligible patients will receive re-challenge chemotherapy (either carboplatin AUC 4 on day 1 plus etoposide 80 mg/m2 days 1-3 or carboplatin AUC 5 on day 1 plus etoposide 100 mg/m2 days 1-3, at investigator's choice) plus atezolizumab 1200 mg flat dosing on day 1 every 3 weeks until PD, unacceptable toxicity or to a maximum of 4 cycles (induction phase) followed by atezolizumab 1200 mg flat dosing every 3 weeks (maintenance phase) until completion of 1 year of maintenance (up to 18 cycles), progressive disease, unacceptable toxicity, patient refusal or loss of clinical benefit (investigator's choice), whichever occur first. Subjects will attend clinical visits at regular intervals to receive trial treatment and for efficacy and safety assessments. All subjects will be monitored continuously for any AE while on study treatment. Radiological assessment will be performed by computed tomography (CT) scan at week 6 (± 7 days), at week 12 (± 7 days) and every 12 weeks (± 7 days) thereafter. The duration of the study is expected to be a maximum of 45 months. The study recruitment period is expected to be approximately 24 months, maximum treatment duration will be 15 months (3 months of induction and 12 months of maintenance), and subsequent survival follow-up will be a maximum of 6 months.

Effectiveness of an N-acetylcysteine and Urea-based Cream in Prevention of Capecitabine-induced HAND-foot Syndrome in Breast Cancer Patients

Breast cancer (BC) is the most frequent tumour in women. To date, among the available treatments, the use of Capecitabine, an oral prodrug of fluorouracil, has been shown activity in different setting. In advanced disease, Capecitabine is often used as monotherapy in patients pretreated with anthracycline, taxane or both. One of the most frequent toxicities reported by patients receiving capecitabine is hand-foot syndrome (HFS), with an incidence of grade 3 HFS of 28%. HFS, also known as palmar-plantar erythrodysesthesia syndrome, is initially characterized by palmoplantar numbness, tingling, or burning pain. These symptoms usually coincide with sharply demarcated erythema with or without edema, cracking, or desquamation. In advanced stages, blistering and ulceration may occur. Although HFS is not considered life threatening, it can be painful and interfere with daily activities, thusseriously compromising quality of life (QoL), therefore this toxicity is considered dose limiting.Moreover, consistent with the theory that Capecitabine and its metabolites induce an inflammatory effect, the use of COX-2 inhibitors is an emerging strategies, but more evidence are needed from largest study to confirm their efficacy. Similarly, N-acetylcysteine (NAC), an antioxidant, mucolytic and nephroprotective agent, that affects pathways involved in inflammatory conditions and that has demonstrated to be effective in several dermatologic conditions, could be useful in the management of Capecitabine-induced HFS. From this arises the present study that has the objective of evaluating the role of NAC plus urea-based cream in the prevention of Capecitabineinduced HFS in patient affected by breast cancer.