Clinical trials

Hemostatic agents are widely used in cardiac and vascular surgery to support intraoperative bleeding control. Despite their clinical relevance and substantial economic impact, little is known about real-world patterns of use, adherence to evidence-based recommendations, and the alignment between clinicians' perceived knowledge and actual decision-making. HAEMOVAX is a single-center mixed-methods observational study conducted at IRCCS Galeazzi-Sant'Ambrogio Hospital, Milan, Italy. The study combines an anonymous survey of cardiovascular surgeons with a retrospective audit of institutional hemostatic agent consumption. The primary objective is to evaluate the appropriateness of hemostatic agent selection using a Knowledge-Practice Alignment Score (KPA-Score) derived from standardized clinical vignettes based on current EACTS and ESA recommendations. Secondary objectives include assessment of usage patterns, barriers to appropriate use, concordance between declared practice and real-world consumption, and opportunities for evidence-based standardization.

High-flow nasal cannula (HFNC) is a widely used noninvasive respiratory support technique for patients with acute respiratory failure (ARF). It provides heated and humidified oxygen at high flow rates, improving oxygenation, reducing respiratory effort, and enhancing patient comfort. International guidelines recommend HFNC over conventional oxygen therapy in hypoxemic ARF. However, there is significant variability in clinical practice regarding HFNC discontinuation, and no standardized weaning criteria currently exist. Prolonged HFNC use may increase hospital stay and healthcare costs, while premature discontinuation may lead to respiratory deterioration and the need for further ventilatory support. Previous studies suggest that successful HFNC weaning may be predicted by a Fraction of inspired oxygen (FiO₂) ≤40% and a Respiratory rate-Oxygenation index (ROX index) ≥9.2. The ROX index is calculated as the ratio of peripheral oxygen saturation (SpO₂) divided by fraction of inspired oxygen (FiO₂) to respiratory rate. The primary objective of this study is to compare a standardized HFNC weaning strategy based on ROX index and FiO₂ thresholds with usual clinical practice based on physician judgment. The primary outcome is weaning failure at the first attempt, defined as the need for HFNC reinstitution, noninvasive or invasive mechanical ventilation, or death within 48 hours after discontinuation.

Bronchoscopy is an essential technique, routinely used in the differential diagnosis workup of many Interstitial Lung Diseases (ILDs) and in referral centres is a common procedure. Bronchoalveolar lavage (BAL), bronchial and transbronchial biopsies with forceps and cryoprobes, and lymph node sampling with endosonography represent the most used sampling techniques in these patients. However, patients with ILDs refer to medical attention in a wide range of clinical conditions from mild functional impairment, with absent or few respiratory symptoms, to severe lung involvement with low exercise tolerance and/or chronic respiratory failure. In these patients, a balance between benefits and risk, i.e. to the safety and diagnostic utility of bronchoscopy should be always carefully evaluated. Moreover, there is a wide variability in adverse events entity and frequency depending by procedures performed during bronchoscopy. Despite its crucial utility, only few data are available in the literature on the safety of bronchoscopy in patients with ILDs and limited data on the utility and safety of this sampling technique are present in patients with AE-ILDs. The primary aim of this study is to assess the overall rate of complications occurring within 24 hours after bronchoscopy. Study rate and type of complications occurring during the endoscopic procedure, within 30 days after bronchoscopy, in patients with AE-ILDs, among fibrotic Vs non-fibrotic ILD, and according to each employed sampling technique will be also recorded.

During bronchodilator tests, it's common to ask patients with asthma or chronic obstructive pulmonary disease (COPD) to take bronchodilator therapy by inhaling after a maximal exhalation, when the respiratory system volume equals the residual volume. The same maneuver is required for the chronic therapy. Nevertheless, in patients with COPD the distribution of ventilation is more heterogeneous, especially when lung volumes are closer to residual volume . It is therefore predictable that the distribution of air volume containing bronchodilator that has been inhaled at residual volume is more heterogeneous than at higher volumes, such as at functional residual capacity. Accordingly, the bronchodilator can be preferentially distributed in more open airways than in less patent ones, with a heterogeneous distribution of the medication. Therefore, the overall bronchodilation should be greater when the drug inhalation is performed at functional residual capacity than at residual volume. It is common knowledge that the effectiveness of bronchodilator therapy with pMDI in subjects with COPD is greatly affected by the inhalation technique, which can be difficult to perform for many patients. Therefore, in addition to the possibility that inhalation of bronchilation therapy at residual volume could lower the drug effectiveness, this maneuver complicates the sequence of actions required to the patient, enhancing the risk of errors and decreasing the aderence to treatment. The aim of this study is to investigate whether the inhalation of a bronchodilator at different lung volumes can affect its effectiveness in terms of respiratory function, in patients with COPD. Assuming that the bronchodilator effectiveness is equal or greater when inhaled at functional residual capacity rather than at residual volume, the inhalation maneuver can be simplified for patients with COPD.

It is a phase IV, prospective, interventional, single blind, randomized, crossover trial in which the investigators will evaluate the effects of a 4-week treatment with doxofylline 400 mg bid, in add-on to maximal inhalation therapy, in clinically stable COPD patients.

This case-control study investigates fatigue induced by prolonged gum mastication in individuals with temporomandibular disorders (TMD). The study addresses two primary questions: How does self-reported fatigue, measured with a visual analogue scale (VAS), change during sustained chewing? How do static and dynamic surface electromyographic (sEMG) parameters evolve over the same period? Participants with TMD will be compared with healthy controls to determine group differences in perceived fatigue and EMG responses. All participants will undergo baseline EMG assessment, then chew sugar-free gum continuously for 3 minutes, alternating sides without rest. After each 3-minute interval, static and dynamic EMG recordings will be obtained and participants will rate their fatigue on the VAS. This cycle may be repeated up to six times (maximum 18 minutes). Participants are free to stop chewing at any time if fatigue becomes intolerable.

Specific Aims : The aim of this prospective randomized controlled single-blind clinical trial was to evaluate the safety and efficacy of autologous microfragmented lipoaspirate tissue in arthroscopic rotator cuff repair. The primary goal of this study was to test the following hypothesis: an intraoperative injection of autologous microfragmented adipose tissue processed with an enzyme-free technology could improve the clinical outcomes of single-row arthroscopic rotator cuff repair in terms of points in the Constant-Murley score (CMS) collected at least 5 years after surgery. Background and Significance: Rotator cuff surgery was initially proposed at the end of the 19th century and evolved then from open to arthroscopic techniques, rising quickly from a minor niche to a fully recognized subspecialty. To improve clinical and functional results and reduce the retear rate, new fixation techniques and biological solutions to enhance tendon healing are being developed at a fast pace, as shown by the dramatic increase in the number of articles published per year. Biological solutions to enhance rotator cuff healing include growth factors and platelet-rich plasma, as well as mesenchymal stem cells (MSCs) and their derivatives. MSCs are believed to enhance tissue healing mainly through stimulation of local cells via paracrine mechanisms and anti-inflammatory and/or immunomodulatory activity, thus creating a suitable microenvironment for tissue repair. Autologous microfragmented lipoaspirate tissue has been recently introduced in orthopaedics as an easily available source of adipose derived MSCs (ADSCs) to support and accelerate tissue regeneration. Lipoaspirates contain human ADSCs and produce growth factors, such as platelet-derived growth factor, fibroblast growth factor, transforming growth factor beta, and vascular endothelial growth factor, which play important regulatory roles in cellular functions, including adhesion, chemotaxis, proliferation, migration, matrix synthesis, differentiation, and angiogenesis. Herewith, autologous microfragmented lipoaspirate tissue is expected to optimize the microenvironment for tendon regeneration. Among many approaches, devices relying on nonenzymatic methods and avoiding the use of additives and other additional manipulations (eg, centrifugation) allow one to harvest, process, and obtain autologous microfragmented lipoaspirate tissue directly in the operative theatre under sterile conditions. This permits immediate use in the same surgical intervention without delays owing to the difficulty of an ex vivo cell expansion and the complexity of the current good manufacturing practice requirements for preparing cells for therapeutic use. Although several animal studies have been published showing promising results for the use of ADSCs in enhancing the healing of rotator cuff tears, minimal evidence describing augmentation of rotator cuff treatment with lipoaspirate. Preliminary Studies/Progress Report: This study is a prospective, randomized, double-blind, controlled clinical trial and represents the final follow-up of an our previous study with short follow-up (2 years). The previous study demonstrated that the intraoperative injection of autologous microfragmented adipose tissue is safe and effective in improving short-term clinical and functional results after single-row arthroscopic rotator cuff repair. Nevertheless, no significant differences emerged between the groups in terms of rerupture rate, complication rate, number of adverse events, and mid-term clinical outcomes. A previous in vitro study showed that autologous microfragmented adipose tissue significantly increases the proliferation rate of human tendon stem cells without altering their stemness and differentiation capability. Moreover, treated cells increase the expression of VEGF, which is crucial for the neovascularization of the tissue during the healing process. Research Design and Method: At least 5 years after surgery, all enrolled patients in the previous study will be call again and will be asked to complete the ASES, SST, and VAS questionnaire and they will undergo a clinical examination, including the CMS and measurement of isometric strength in shoulder forward flexion, abduction, and external rotation. All strength measures will be performed in triplicate with a dynamometer. During the same assessment day, the patients would be evaluated with MRI of the operated shoulder in order to assess tendon integrity and calculate rerupture rate according to the classification proposed by Sugaya (types IV and V defined as retears). Atrophy of the supraspinatus muscle belly was evaluated according to Warner and fatty degeneration was classified according to Fuchs.

Mowat-Wilson Syndrome (MWS) is a rare syndrome characterized by the presence of facial gestalt and delayed psychomotor development, variably associated with intellectual disability, epilepsy, Hirschsprung's disease (HSCR) and multiple congenital malformations. Although there is evidence of the presence of dental and craniofacial anomalies in MWS, little epidemiological data is available to date. The goal of this observational study is to assess oral health and dento-facial phenotype of people affected by Mowat-Wilson Syndrome (MWS). In addition, the Oral Health Related Quality of Life (OHRQoL) will be investigated.

Idiopathic Pulmonary Fibrosis (IPF) is a chronic, fibrosing, and progressive lung disease of unknown cause, whose incidence increases proportionally from the age of 60. It is characterized by a poor prognosis. Antifibrotic therapy can slow the progression of the disease and reduce mortality, but the life expectancy is less than 7-10 years in the vast majority of patients with IPF. There are no studies in the literature that have evaluated the presence of small airway disease in patients with IPF prior to the initiation of pharmacological therapy, using the nitrogen washout test. This test is currently considered the only non-invasive method capable of detecting ventilation inhomogeneity and closing volume, which are indicators of small airway dysfunction. The investigators carried out an Italian prospective, observational, multicenter study with the primary aim to assess the prevalence of small airway disease measured by the nitrogen washout test (evaluating the following functional parameters: phase 3 slope, closing volume, closing capacity, closing volume/vital capacity, closing capacity/total lung capacity, and phase 4 slope) in a group of patients with IPF at the time of diagnosis, before the initiation of antifibrotic therapy. During outpatients visits clinical, functional and radiological data will be collected. Results will be compared to an healthy control group matched with IPF population. Variations in small airways disease parameters will be assessed after one year of antifibrotic treatment.

Lymphangioleiomyomatosis (LAM) is a rare lung disease, linked to Tuberous Sclerosis Complex (TSC) or occurring sporadically, and involves abnormal mTORC1 activation. LAM cells are neoplastic, and recent focus has turned to extracellular vesicles (EVs), which mediate tumor progression and may serve as biomarkers. This study, conducted at the Pulmonology Unit of ASST Santi Paolo e Carlo and the Pharmacology Laboratory of the University of Milan, will analyze the characteristics of serum EVs in patients with LAM and TSC. During scheduled outpatient visits, clinical and functional data and blood samples will be collected. Plasma will be separated, and EVs will be isolated via centrifugation. EVs will be analyzed for size, concentration, and molecular content (proteins, lipids, nucleic acids). The results obtained will be collected and correlated with the clinical and functional data.

Temporomandibular disorders (TMD) are among the most common causes of chronic pain worldwide. It is estimated that about 5-12% of the global population is affected, and some conditions, such as arthritis, may be causative factors. Depending on severity, the joints involved can affect multiple functions of the masticatory system, such as the ability to speak, chew, swallow, limit facial expressions, and even breathe. Moreover, most patients with TMD may report painful conditions in other parts of the body, with comorbidities including chronic fatigue syndrome, chronic headache, endometriosis, fibromyalgia, interstitial cystitis, irritable bowel syndrome, back pain, sleep disorders, and vulvodynia. Another significant condition that frequently occurs alongside TMD is psychological distress in the form of anxiety and/or depression. The study proposed by this research protocol aims to investigate the presence of TMD and associated psychological/psychiatric disorders such as anxiety and depression. The innovative value of the research lies in evaluating whether the association between these disorders may lead to neuroplastic changes at the brain level, which could guide targeted therapies. Only a few studies in the literature have explored this possible association, with inconclusive and conflicting results. The study will be prospective in design, based on reference clinical/diagnostic criteria and functional neuroimaging.

Foot hyperpronation is a common postural condition that can lead to pain, deformities (such as hallux valgus), and muscular issues. This problem is especially relevant among adults who spend long hours standing, such as healthcare workers. Custom-made foot orthoses with a medial wedge have proven effective in improving comfort and correcting certain biomechanical alterations, even in asymptomatic individuals. The study described has two main objectives: * to validate the Italian version of the Foot Health Status Questionnaire (FHSQ), already validated in English and Spanish, by assessing its reliability and reproducibility as a tool to measure foot health. * through a pilot study, to analyze the effects of using specific professional footwear in healthcare workers with hyperpronation, evaluating perceived benefits in terms of pain reduction and postural improvement.

This study aims to assess the effects of physical activity in counteracting muscle aging. The increasing life expectancy worldwide has led to a rise in age-related muscle decline, which negatively impacts strength, function, and overall quality of life. Sedentary lifestyles further accelerate this process, increasing the risk of frailty, falls, fractures, and disability. This randomized controlled trial (RCT) will investigate whether a structured exercise program can help reduce muscle deterioration. The study will involve 200 participants, divided into three age groups: i) Young adults (18-35 years); ii) Middle-aged adults (35-65 years); iii) Older adults (\>65 years). Participants will be assigned to either a physical activity intervention group or a control group. The intervention group will follow a 48-week structured program including, muscle-strengthening sessions (bodyweight exercises at home) and aerobic sessions (moderate-intensity cardio exercise). The control group will not receive any exercise prescription. The primary objective is to evaluate whether physical activity improves muscle strength, measured through handgrip strength at 12 and 48 weeks. Secondary objectives include: i) assessing changes in muscle mass, function, and quality of life; ii) measuring improvements in physical performance (aerobic capacity, balance, and mobility tests); iii) evaluating psychological and cognitive well-being. This 48-week trial will consist of: i) baseline assessments (body composition, strength tests, physical and cognitive evaluations); ii) intervention period (12 weeks of structured training for the experimental group); iii) follow-up assessments (at 12 and 48 weeks). All participants will undergo periodic evaluations, including anthropometric and body composition measurements (weight, BMI, muscle mass), aerobic and muscle strength tests (handgrip, knee extension, 1-rep max tests), functional mobility assessments (six-minute walking test, chair-stand test), psychological and cognitive evaluations (mood profiles, quality of life surveys, cognitive tests). Engaging in regular exercise may help participants: i) maintain muscle mass and strength; ii) improve physical function and balance; iii) enhance overall well-being and independence; iv) reduce the risk of age-related disabilities. Additionally, the study aims to provide valuable insights into the role of exercise in healthy aging, helping healthcare providers develop personalized interventions for older adults.

The study "Cornelia de Lange Syndrome: assessing positive effects of Lithium treatment - CLoSER" aims to evaluate the effectiveness on behavioral modifications of lithium carbonate therapy in patients with Cornelia de Lange syndrome (CdLS). CdLS is a rare genetic disease caused by autosomal mutations dominant or X-linked. The prevalence of CdLS is estimated to be between 1:10,000-30,000 newborns, but it is probably underestimated because the most cases mild ones may go undiagnosed. This syndrome is characterized by slow growth before and after birth with intellectual disability and short stature, from major malformations such as facial anomalies, neurological disorders, gastrointestinal and musculoskeletal malformations. To date, for these patients only targeted medical and surgical therapeutic interventions are recommended for improving the quality of life. No drug therapy is validated for the cognitive/behavioral disorders. It has been shown that lihium-dependent activation of the WNT pathway is able to recover the Abnormal phenotype in many CdLS models. Lithium is already widely used in psychiatry and has a long history of clinical efficacy. Recently some studies are evaluating the effect of lithium in patients with characteristics common to CdLS showing promising results . This trial intends to transfer the preliminary data obtained from in vitro and in vivo studies on patients with CdLS. Given the currently untreatable nature of the syndrome, this treatment could represent a possible therapeutic strategy aimed at improving the behavioral and intellectual disabilities typical of CdLS.

Conflicting evidence exist in the literature on the utility of bronchoscopy in patients with haemoptysis and negative/non-diagnostic chest CT scan. The primary aim of this prospective, observational, multicenter study is to evaluate the utility of bronchoscopy in patients with haemoptysis and negative/non-diagnostic CT scans. Secondary aims are related to the utility of bronchoscopy to detect occult malignancies, the source of the bleeding and the clinical features of the cohort

Standard anti-seizure medications have limited efficacy in seizure control in cyclin-dependent kinase-like 5 deficiency disorder (CDD). The study will investigate whether targeting the gut-microbiota-brain axis in CDD patients can alleviate seizures and ameliorate other comorbidities.

Background Lower-grade-gliomas affect young patients, thus the longest progression-free-survival (PFS) with a high level quality of life is crucial. Surgery most significantly impacts on tumor natural history, postponing recurrence, improving symptoms, decreasing the need of adjuvant therapies, with extent of resection, gross-total and supra-total (GTR and STR), strongly associating with longest PFS. Achievement of GTR or STR depends on the degree of functional reorganization induced by glioma. Consequently, a successful treatment fostering neural circuit reorganization before surgery, would increase the chance of GRT/STR. Hypothesis The plastic potential of motor system suggests that reorganization of circuits controlling hand movements could be presurgically fostered in LGG patients by enhancing plasticity with up-front motor-rehabilitation and/or by decreasing tumor infiltration with up-front chemotherapy. Advanced neuroimaging allows to infer the neuroplasticity potential. Intraoperative assessment of the motor circuits functionality will validate reliability of preoperative analyses. Aims The project has 4 aims, investigating: A) the presurgical functional (FC) and structural (SC) connectomics of the hand-motor network to picture the spontaneous reorganization and the influence of clinical, imaging and histomolecular variables; B) the dynamic of FC and SC after tumor resection; C) changes in FC and SC maps after personalized upfront motor rehabilitation and/or chemotherapy; D) the effect of FC and SC upfront treatment on the achievement of GTR/STR preserving hand dexterity. Experimental Design Resting-state fMRI and diffusion-MRI will provide FC and SC maps pre- and post-surgery; personalized up-front motor rehabilitation and/or chemotherapy will be administered; Intraoperative brain mapping procedures will generate data to validate the maps. Expected Results 1. Provide a tool to render the motor functional reorganization predictive of surgical outcome. 2. Identify demographic, clinical and imaging variables associated with functional reorganization. 3. Describe the gain induced by up-front treatment. 4. Distinguish "patterns" predicting chance for GTR/STR from "patterns" suggesting need for up-front treatment. Impact On Cancer Results will increase the achievement of GTR/STR, preserving motor integrity, with dramatic impact on LGGs natural history.

Type 1 Diabetes (T1D) is a chronic autoimmune disease, with a genetic background, resulting from the immune-mediated destruction of beta cells of the pancreas. It can lead to fatal short-term and long-term complications, especially if it is diagnosed late. Three stages of the disease can be identified: Stage 1 is defined by the presence of two or more anti-islet autoantibodies (GAD65, ICA, IA-2, ZnT8) with normoglycemia, Stage 2 shows progression to dysglycemia (impaired glucose tolerance) in the setting of two or more anti-islet autoantibodies, Stage 3 occurs when a patient meets ADA criteria for the diagnosis of diabetes. It's been demonstrated that Teplizumab (an Fc receptor nonbinding anti-CD3 monoclonal antibody) delays the transition from pre-symptomatic T1D (stage 2) to overt T1D (stage 3). Also Sitagliptin, a DPP4 inhibitor, has been proved effective in inhibiting inflammation in T1D both in vitro in T1D mice, and in vivo in Latent autoimmune diabetes in adults (LADA) patients. Furthermore, it has been confirmed that Sitagliptin reduces the prevalence of worse forms of acute GVHD after myeloablative allogeneic hematopoietic stem-cell transplantation. The study aims to investigate if Sitagliptin can have a delaying effect on progression to overt T1D, on the account of its anti-inflammatory properties. The cohort is made of screened relatives of T1D patients, who are classified as high-risk of developing T1D. Screening relatives of T1D patients for dysglycemia and anti-islet autoantibodies. Selecting the patients in Stage 2 Pre-symptomatic T1D (dysglycemia and at least two types of autoantibodies) and then beginning therapy with Sitagliptin, while monitoring their glucose metabolism with a Continuous Glucose Monitoring (CGM) system.

The main aim of the present study is to investigate implant success rate after 5 years of function of immediate (Test group; within 7 days of implant placement) versus delayed (Control group; 8 weeks after implant placement) loading of two-pieces zirconia implant, placed in pristine bone without bone regeneration. Implant success rate will be defined according to Buser's criteria. Secondary endpoints: Marginal bone level (MBL) evaluation by means of standardized radiographs; Clinical evaluation of biological (e.g. Plaque Index, PI; Probing Pocket Depth, PPD, Bleeding on Probing, BOP; suppuration upon probing/palpation) and prosthetic/technical complications; Clinical evaluation of soft tissue width, keratinized tissue, marginal and interproximal soft tissue recession; Patient reported outcome measures (PROMs) by questionnaire administration:

The present study will evaluate the difference in terms of keratinazed mucosa (KM) in computer guided implant placement with immediate loading, comparing a flapless approach to flap surgery with connective tissue graft.