Clinical trials

Major pulmonary resection is associated with high postoperative morbidity and mortality, mainly due to cardiorespiratory complications. Right ventricular (RV) function is closely related to pulmonary artery pressure and tone, and it is particularly sensitive to changes in afterload. An increase in RV flow resistance can lead to acute RV dilation and reduced left ventricular compliance, potentially progressing to cardiogenic shock. In a previous study (RIVER), it was observed that increased afterload following open thoracic surgery reduces RV function, although this impairment remains subclinical. The aim of this study is to investigate the same parameters in patients with severe cardiovascular comorbidities undergoing pulmonary resection via minimally invasive approaches (VATS and robotic surgery) compared to open thoracotomy.

The ACT-FAST study aims to compare commercially available Rapid Antimicrobial Susceptibility Testing (R-AST) tools with the current standard of care for patients with Bloodstream Infections (BSI). The primary objective is to evaluate whether "early targeted" antibiotic prescriptions, guided by these rapid tests, can improve antimicrobial stewardship and patient clinical outcomes. To facilitate the evaluation of various diagnostic tools-including those currently on the market and those emerging in the near future-this study utilizes an adaptive clinical trial platform. This flexible design allows for the continuous assessment of different R-AST technologies within a single master protocol, ensuring that the most effective diagnostic strategies are identified efficiently.

Some patients with head and neck cancer may develop a tumor recurrence in an area that has already been treated with radiotherapy. In these situations, surgery is not always possible, and giving radiotherapy again can be challenging because nearby healthy tissues and organs may already have received high radiation doses. The REPROton-HN study is evaluating the use of proton therapy for these patients. Proton therapy is a type of radiation treatment that can deliver radiation more precisely to the tumor while reducing exposure to surrounding healthy tissues. The aim of the study is to better understand how safe and effective proton therapy is when used as a second course of radiation treatment. Researchers will monitor side effects, tumor control, survival, and patients' quality of life. The results may help improve treatment planning and identify which patients are most likely to benefit from proton therapy in the future.

This observational study will analyze data already collected by the investigators as part of their routine clinical practice from patients with acute respiratory failure (ARF) treated with mechanical ventilation. The study itself does not require any specific intervention. Mechanical ventilation can save the lives of patients with ARF. However, if used improperly, it can exacerbate lung disease and worsen outcomes (Slutsky et al.). Despite decades of animal and clinical research, it remains unclear how to establish the positive end-expiratory pressure (PEEP) during mechanical ventilation to reduce the risk of lung damage. Several methods have been suggested, but none have consistently proven superior to the others (Sahetya et al.). As part of their routine clinical practice, the investigators study the responses to different PEEP levels of patients with ARF undergoing mechanical ventilation by integrating information from various techniques, each examining different aspects of lung morphology and physiology. The methods the investigators use include lung computed tomography (CT) and electrical impedance tomography (EIT). Lung CT is the reference technique for measuring the morphological response to PEEP (Gattinoni et al.). It quantifies the volume of the hyperinflated and non-aerated lung, both of which are related to the risk of mechanical ventilation causing damage (Slutsky et al.). Lung EIT monitors the functional response to PEEP in terms of changes in regional compliance across different PEEP levels. Allegedly, an increase in compliance when PEEP is decreased reveals overdistention, the functional correlate of (worrisome) hyperinflation, at the higher PEEP. A decrease in compliance when PEEP is decreased signals new collapse, the functional correlate of (worrisome) loss of aeration (Franchineau et al.). In the Unit where the investigators work, patients with ARF treated with mechanical ventilation are routinely studied as follows. First, a lung CT with a PEEP of 20 cmH2O and then of 5 cmH2O is obtained. Thereafter, a decremental PEEP test is performed with the EIT, where PEEP is decreased from 20 cmH2O down to 5 cmH2O in steps of 2 or 3 cmH2O. Finally, results are analyzed and compared offline. At the lung CT, decreasing PEEP from 20 to 5 cmH2O is always associated with some decrease in the volume of the hyperinflated lung and some increase in the volume of the non-aerated lung. However, the magnitude of these two effects varies among individuals, and the net response may be defined as the difference between those two competing effects. If the decrease in the volume of the hyperinflated lung is greater than the increase in the volume of the non-aerated lung, the overall response (i.e., less hyperinflation) can be considered positive. PEEP should then be set closer to 5 than to 20 cmH2O. Diversely, if the decrease in the volume of the hyperinflated lung is smaller than the increase in the volume of the non-aerated lung, the overall response (i.e., more loss of aeration) can be considered negative. PEEP should then be set closer to 20 cmH2O (Protti et al.). Similarly, at the lung EIT, decreasing PEEP from 20 to 5 cmH2O is always associated with compliance improvement in some regions (i.e., less overdistension) and worsening in others (i.e., more collapse). Again, the magnitude of these two opposite effects varies among individuals. According to most experts on lung EIT, PEEP should be set at the level where both overdistension and collapse are minimized (the so-called "best" PEEP) (Jonkman et al.). Lung CT requires transfer to the radiology unit, exposure of the patient to radiation, and complex analysis offline. By contrast, lung EIT is virtually risk-free, and analysis can be performed using an automatic algorithm. Nevertheless, lung EIT is less well validated than lung CT. For instance, the assumption that a decrease in compliance in response to a decrease in PEEP is due to new collapse has been questioned (Protti et al., Chiumello et al., Menga et al.). So far, lung CT remains the reference technique for studying individual responses to PEEP, while lung EIT requires further validation. This study aims to verify whether the "best" PEEP identified using lung EIT is strongly associated with the net response assessed using lung CT, when PEEP is decreased from 20 to 5 cmH2O in patients with ARF treated with mechanical ventilation. If so, this would strengthen the rationale for using the lung EIT (which is safer and simpler than the lung CT) to set PEEP.

Stage II seminoma is a type of cancer that is usually highly curable and most often affects young men. Radiotherapy is an effective treatment, but it can sometimes cause side effects in the long term and, rarely, increase the risk of developing another cancer later in life.For this reason, more targeted treatments are being explored, such as proton therapy (PBT). This type of radiotherapy uses protons to better focus the treatment on the tumor while reducing exposure to the surrounding healthy tissues.The goal is to treat the cancer effectively while minimizing side effects as much as possible.

This study aims to explore the effectiveness of perioperative Oral Nutritional Supplementation (ONS) combined with an optimized, tailored diet in reducing the risk of postoperative complications and improving the nutritional status of colorectal cancer patients scheduled for curative colorectal resection.

Bladder cancer is the most common type of urothelial cancer. When the disease has spread to other parts of the body (metastatic disease), the prognosis is often poor, because there are only a few effective treatment options available. At the moment, standard treatment mainly includes systemic therapies, such as chemotherapy and immunotherapy (immune checkpoint inhibitors). These treatments act on the whole body. However, the use of local treatments, such as stereotactic radiotherapy, has not been well studied in bladder cancer. Stereotactic radiotherapy is a type of radiation treatment that delivers very high doses of radiation to the tumor in a small number of treatment sessions. This technique is already widely used to treat a limited number of metastases (called oligometastases) from other types of cancer. The aim of this study is to understand whether stereotactic radiotherapy is also effective and safe for treating oligometastases coming from bladder cancer.

This is a phase III randomized trial with the aim to compare preoperative HSRS to postoperative HSRS in patients with large at least one BMs from solid tumors suitable for surgical resection.

When people become seriously ill, their bodies can be affected in many ways beyond the original disease. One well-known complication in patients treated in intensive care units (ICUs) is the development of severe muscle weakness caused by damage to muscles and nerves. This condition is called critical illness-related weakness and includes disorders of the nerves (neuropathy), the muscles (myopathy), or both. These problems can make it difficult for patients to move, walk, or even breathe independently, and recovery can take months or longer. So far, most research on this type of weakness has focused on patients who were treated in ICUs. However, many hospitalized patients outside the ICU-such as those admitted to internal medicine wards or semi-intensive care units-can also experience severe infections, organ failure, inflammation, prolonged bed rest, and metabolic stress. These are the same risk factors known to cause nerve and muscle damage in ICU patients. Despite this, weakness occurring outside the ICU is often overlooked, attributed simply to "deconditioning" or prolonged bed rest, and not properly investigated. The CRI-WEAK-OUT study aims to better understand whether critical illness-related weakness also occurs in hospitalized patients who are not admitted to the ICU, how often it happens, how severe it is, and what factors increase the risk of developing it. This is a prospective observational study, meaning that patients will be followed over time during and after their hospital stay, without changing their usual medical care. The study will include about 600 adult patients hospitalized for acute illnesses in non-ICU wards across several Italian hospitals. Half of the participants will have signs of organ failure during hospitalization, while the other half will serve as a comparison group without organ failure. All participants will undergo careful clinical evaluations shortly after hospital admission and again before discharge. Doctors will assess muscle strength, level of disability, independence in daily activities, and overall frailty using standardized and widely accepted scales. Six months after discharge, patients will be contacted by phone to evaluate their recovery and quality of life. If a patient develops new or worsening muscle weakness during hospitalization, more detailed tests will be performed. These include electrical tests of nerves and muscles to understand whether the weakness is caused mainly by nerve damage, muscle damage, or both. In a subgroup of patients, additional blood samples will be collected to measure substances linked to inflammation and nerve injury. These biological markers may help doctors recognize the condition earlier and predict recovery. By collecting detailed clinical, electrical, and biological information, the study aims to answer several important questions: * How common is critical illness-related weakness outside the ICU? * Which patients are most at risk? * How does this condition affect recovery and long-term independence? * Can blood markers help identify patients with nerve or muscle damage? The results of the CRI-WEAK-OUT study may improve awareness of this under-recognized condition, promote earlier diagnosis, and help clinicians plan better prevention and rehabilitation strategies. Ultimately, this research could lead to improved care, faster recovery, and better quality of life for many hospitalized patients who currently experience unexplained weakness after acute illness.

Radiotherapy (radiation treatment) is often used to treat lung cancers and lung tumors that have spread from other cancers. It can be very effective, especially in early-stage lung cancer or when there are only a few tumor sites. Even so, some patients later develop a local recurrence, meaning the cancer comes back in the same area that was previously treated with radiation. When this happens, treatment options are limited. Surgery can sometimes remove the recurrent tumor, but many patients are not able to have surgery because of their general health or because the tumor is difficult to remove. For these patients, a second course of radiotherapy (called re-irradiation) may be the only possible treatment. One type of radiotherapy, called stereotactic body radiotherapy (SBRT), delivers very high doses of radiation very precisely. SBRT has been used successfully as a second treatment after standard radiotherapy in some patients. However, there is very little information about using SBRT again in patients who already received SBRT the first time. Because only small studies have been done and the patients were very different from each other, doctors still do not know enough about how safe and effective a second SBRT treatment is. In particular, it is still unclear whether giving another high-dose radiation treatment is possible without causing serious side effects. More research is needed to better understand this option and help guide treatment decisions for patients.

Oligometastatic breast cancer is a condition in which breast cancer has spread to a small number of other parts of the body. Patients with this type of disease may live longer than those with more widespread metastases. In addition to standard treatments that act on the whole body, such as chemotherapy or hormonal therapy, these patients might also benefit from local treatments that directly target the cancer spots. One of these local treatments is stereotactic body radiotherapy (SBRT), a non-invasive radiation treatment that delivers high doses of radiation in a few sessions. In the past, most of the evidence about the benefit of local treatments came from surgery. More recently, there has been growing interest in SBRT because it does not require surgery. However, the results of studies so far have not been consistent.The goal of this multicenter retrospective study is to better understand whether SBRT can improve disease control and survival in patients with breast cancer that has spread to a limited number of sites outside the brain.

The primary aim of the study is to investigate whether video-based education and exercise-program is non-inferior to in-person instructions in improving pain-related self-efficacy in patients undergoing arthroscopic partial meniscectomy in a day-hospital setting. Secondary aims are to explore the potential superiority of the video-based program compared to in-person instructions in reducing disability and kinesiophobia in the same patient population.

Proton therapy is a cancer treatment, similar to the more commonly used radiation therapy. It uses radiation to destroy cancer cells and helps control the disease in the treated area. However, when proton therapy is compared with standard radiation therapy, many studies show fewer side effects and better disease control. This is due to the unique physical properties of the particles used in proton therapy. At present, in Italy, this innovative treatment is available only for selected diseases, as defined by national guidelines. For this reason, it is very important to collect as much data as possible to support the further development of proton therapy and to improve treatment safety and effectiveness.

The study objective is to evaluate the use of Stereotactic Body Radiotherapy (high dose of radiation in a few fractions) to cure primary renal cancer in those patients that are not indicated to surgery (high risk of complications, refusal of the patient). This therapy is already used in clinical setting for many tumors with good tolerance as it is not invasive, does not require anesthesia and hospitalization making it suitable for elderly people and frail patients. However there are not enough information regarding the use of ablative doses for the cure of renal cancer and for this reason this study aims to support the use of Stereotactic Body Radiotherapy as a standard of care for inoperable primary renal tumor. This is an observational study, so it collects data from clinical pratice only and does not request study specific procedures.

Natural Orifice Specimen Extraction (NOSE) eliminates the need for additional abdominal incisions in minimally invasive colorectal procedures, potentially reducing the risk of wound complications and postoperative pain. In the context of restorative Total Mesorectal Excision (TME), single-stapling (SS) techniques facilitate NOSE through transanal rectal transection, as opposed to the conventional double-stapling technique. This study aims to explore the potential advantages of NOSE combined with SS anastomosis compared to conventional abdominal extraction in minimally invasive restorative TME.

Radiotherapy remains a cornerstone of oncology care, particularly for rare or orphan cancers and chronic oncologic and rare non oncologic conditions, where precision and individualized treatment planning are necessary. Advances in imaging technologies are crucial to overcome the challenges posed by these cases, especially in achieving accurate tumor delineation and dose delivery. Photon-counting CT (PCCT) represents a transformative step forward in imaging technology. Unlike conventional energy-integrating CT, PCCT offers a) superior spatial resolution, enabling clearer visualization of tumor margins and fine anatomical structures, b) enhanced tissue characterization, allowing better differentiation between tumor tissues and normal tissue; c) spectral imaging capabilities, facilitating improved dose calculations. These attributes are particularly advantageous in high-precision radiotherapy techniques, such as stereotactic body radiotherapy (SBRT) or proton therapy, where small errors in target delineation or dose delivery can significantly impact treatment outcomes. However, very limited data reporting the clinical use of PCCT for RT planning are available.

Prostate Cancer (PCa) is the second most common malignancy and the 5th common cause of cancer-related mortality in men worldwide. The majority of patients with PCa is diagnosed with potentially curable disease and its management includes different approaches, such as surgery, Radiation Therapy (RT) and Androgen Deprivation Therapy (ADT), for exclusive use or in combination each other. Randomized clinical trials have shown that moderate hypofractionated RT (i.e., 2.5-4 Gy per fraction) has become a valid alternative to conventionally fractionated RT in patients with PCa. The rationale of hypofractionation is based on the strong radiobiological evidence of the low α/β ratio of PCa cells (1.5-2 Gy) and the greater sensitivity to high dose per fraction. Data suggests that prostate Stereotactic Body Radiation Therapy (SBRT) is an alternative treatment strategy for localized PCa with promising results in terms of disease control and toxicity, not inferior to conventionally fractionated RT. A systematic review of over 6000 men underwent prostate SBRT on prospective studies has demonstrated that this treatment provides favorable patient's quality of life, excellent disease control, and results in minimal serious acute or late toxicity. Almost all the published studies, investigated the role of SBRT for organ-confined low- and intermediate favorable-risk disease. However, the HYPO-RT-PC trial addressed the role of SBRT in the context of unfavorable localized PCa. In this non-inferiority, phase III multicenter trial 1200 patients with either intermediate or high risk PCa were enrolled. The aim of the study was to demonstrate that SBRT (42.7 Gy in 7 fractions, 3 days per week, for 2.5 weeks) is non-inferior to conventional fractionation (78 Gy in 39 fractions, 5 days per week for 8 weeks) regarding failure-free survival, without significant differences in late normal tissues complications. Failure-free survival at 5 years was 84% in both treatment arms; adjusted HR was 1.002, hence ultra-hypofractionation was found to be non-inferior to conventional fractionated RT (given HR limit = 1.338). These results paved the way for the use of SBRT even in patients with unfavorable PCa. One controversial issue is the role of ADT in the setting of SBRT for localized PCa: in conventionally fractionated schedules, short term (4-6 months) and long term (1.5-3 years) ADT are considered the standard of care for unfavorable intermediate and high-risk PCa, respectively. However, in a systematic review/meta-analysis no benefit was found for ADT added to SBRT and similar results were reported also by King et al. in a retrospective study on over 1000 patients. The PACE C trial is one of three cohort of PACE that is multicenter, international phase 3 randomized controlled study. PACE C is set to explore the efficacy of SBRT in combination with ADT for patients with unfavorable intermediate and high-risk PCa and will recruit 1182 patients who will be randomized to receive either hypofractionated RT (60 Gy in 20 fractions) or SBRT delivered with 36.25 Gy in 5 fractions. In this scenario, our study aims to evaluate the safety and efficacy of SBRT (40 Gy in 5 fractions every other day) coupled with ADT (relugolix 18-24 monthsaccording to clinical care) in patients with localized high-risk PCa.

Introduction High-flow oxygen therapy is increasingly used to treat acute respiratory failure (ARF). It can reduce intubation rates without increasing mortality. Moreover, it is better tolerated than other non-invasive respiratory support therapies. However, patients with ARF often make strong breathing efforts, which may cause several harm. They can fatigue the respiratory muscles. They can increase whole-body oxygen consumption and carbon dioxide production. They can cause pulmonary edema. They might also injure the diaphragm and the lungs. For all these reasons, strong breathing efforts should be recognized and treated. During spontaneous breathing, inspiratory muscle contractions produce parallel deflections of the pleural and esophageal pressure (ΔPes), which reflect the magnitude of the effort. Unlike changes in pleural pressure, ΔPes can be easily measured at the bedside using a catheter similar to a typical nasogastric tube. In healthy subjects, ΔPes is only a few cmH2O during quiet breathing but \>10-15 cmH2O during vigorous exercise or carbon dioxide inhalation. In patients with ARF, the upper limit for a "safe" ΔPes is unknown. Nonetheless, according to experts, breathing efforts with a ΔPes \>10-15 cmH2O are probably too strong to be tolerated for a long time. However, esophageal manometry is not widely available. Estimating breathing efforts without it is complex, especially in non-intubated patients. Doctors mostly rely on their gestalt or overall impression. Therefore, it is unsurprising that they may disagree when rating their patients' breathing efforts or debating whether to proceed to intubation. The investigators have recently developed two clinical prediction models for estimating the breathing effort of patients with ARF from a few variables readily available at the bedside. The first, "linear", model estimates the continuous value of ΔPes (in cmH2O) from the presence or absence of COVID-19, arterial base excess concentration (BEa) (in mmol/L), respiratory rate (in bpm), the ratio of the arterial tension to the inspiratory fraction of oxygen (PaO2:FiO2) (in mmHg), and the product term between COVID-19 and PaO2:FiO2. The calibration slope was 1, and the adjusted R2 was 0.39. The second, "logistic", model estimates the probability of ΔPes being \>10 cmH2O (dichotomous outcome) from BEa (in mmol/L), respiratory rate (in bpm), and PaO2:FiO2 (in mmHg). When this model was tested on the same data set used to develop it (apparent performance), the area under the ROC curve (AUROC) was 0.79 (95% CI, 0.73-0.85). At internal validation (optimism-corrected performance), the AUROC was 0.76 (0.71-0.81). The investigators called these models BREF, which stands for BReathing EFfort, but also to the three main predictors: BEa (B), respiratory rate (RE), and PaO2:FiO2 (F). Study aims The main goal of this study is to evaluate the BREF models' predictive performance in a new population. This process is known as "external validation". Additionally, there are two other secondary objectives. The investigators aim to update the BREF models by adding more variables unavailable in the development dataset (method "extension") and compare the accuracy of the BREF models with that of doctors who do not use them in assessing their patients' breathing efforts. Study population Inclusion criteria: * adult (≥18 years of age) patients in the ICU * treated with high-flow oxygen delivered via nasal cannula * equipped with an esophageal balloon as per local clinical practice. Exclusion criteria: * history of chronic lung disease * cardiogenic pulmonary edema * \>96 hours from admission to the participating unit. Methods First, participants will record all the variables needed to estimate ΔPes using the original version of the BREF models. These are the presence or absence of COVID-19, BEa, respiratory rate, PaO2:FiO2, and the product term between COVID-19 and PaO2:FiO2. Moreover, participants will record other variables that may help predict ΔPes based on scientific reasoning. Next, the attending doctor (blinded to the actual ΔPes) will assess the patient's breathing effort based on clinical judgment. Third, the actual ΔPes will be measured with esophageal manometry. Finally, the participants will record the type of respiratory support provided to the patient in the 72 hours following the study, the length of stay in the unit, and the vital status of the patient (dead or alive) at discharge from the unit. Sample size calculation This study aims to enroll 250 patients in approximately two years.

Our AIMING project comprises four core work packages (WPs): WP1. Nation-level randomized controlled trial; WP2. Development of an innovative AI tool; WP3. Novel microsimulation modelling; WP4. Patient inclusion. The nation-level multi-center tandem randomized controlled trial (WP1) will contribute to a better understanding of how the real-time AI algorithm can reduce miss rate of early gastric cancer and dysplasia during gastroscopy. Moreover, the innovation project will contribute to development of a novel AI tool (WP2) that can stratify the risk of gastric cancer by identifying in vivo precancerous conditions. Furthermore, a microsimulation modelling will allow us to predict how the use of AI can prevent gastric cancer and affect cost and patients' burdens. The assessment of the balance between benefits and harms is quite crucial especially for this type of medical device because the value of innovative tools is sometimes overestimated due to stakeholders' enthusiasm (WP3). Finally, we will take care of patients' perspective throughout the study project by including patient organization in both WP1, 2, and 3 (WP4).

The goal of this study is to perform a randomized trial to compare a new through-the-scope suturing system and conventional clips for closure of defect after ESD for 30-60 mm colonic polyps. More precisely, the hypothesis posits that the new through-the-scope suturing system can achieve higher complete closure rates in a shorter time in comparison to conventional clips.

The patient(s) will participate in a clinical study that aims to investigate how the gut microbiota may influence the proper functioning of joints in the body and how it may affect the development of early osteoarthritis (OA), periprosthetic joint infection (PJI), and recovery after total joint replacement. In particular, the prevalence of early OA among patients with gut dysbiosis will be studied (Objective 1). The aim is to identify gut dysbiosis as a potential diagnostic factor for early OA. The study will analyze knee MRI scans and shoulder ultrasound images of 40 patients without musculoskeletal symptoms but with confirmed gut dysbiosis.In addition, the intra-articular microbiota in 50 patients undergoing total knee replacement will be investigated. Serum LPS levels during surgery and fecal microbiota before surgery and during postoperative recovery will be assessed (Objective 2). Postoperative recovery will be assessed based on criteria such as time off crutches and subjective scores. Finally, this will explore the correlation between gut microbiota and contaminating germs in periprosthetic infections. (Objective 3). 40 patients undergoing joint revision surgery for septic failure of a knee or hip replacement and 40 patients undergoing revision surgery for aseptic loosening for PJI will undergo gut microbiota analysis. Comparison between the two groups will allow evaluation of whether PJI causes changes in the gut microbiota. The patients will be included in the study under * objective 1 * objective 2 * objective 3

This prospective observational study aims to investigate the effectiveness and safety of SBRT in the management of oligometastases from rare tumors. In addition, the study aims to identify potential differences in treatment efficacy and toxicity between different types of cancer and to provide valuable information on the use of SBRT in these contexts, potentially leading to better treatment options and outcomes for these patients.

The goal of this clinical trial is to evaluate whether the drug Loncastuximab Tesirine can treat patients with relapsed or refractory Diffuse Large B-Cell Lymphoma (DLBCL) or High-Grade B-Cell Lymphoma (HGBCL) who have not responded to or have had a relapse after CAR-T therapy. The main question it aims to answer is: * Can Loncastuximab Tesirine improve the overall response rate (ORR) in patients who have failed CAR-T therapy? * What are the safety and potential side effects of Loncastuximab Tesirine in this patient group? This is a single-arm clinical trial, meaning all participants will receive the same treatment and there will be no comparison group. Researchers will focus on evaluating the effectiveness of the drug in helping patients achieve a response to treatment, and they will also assess the safety of the treatment. Participants will: * Be treated with Loncastuximab Tesirine through an intravenous (IV) infusion every 3 weeks for up to 8 cycles. * Undergo regular assessments to monitor the response to treatment, including PET-CT scans and blood tests to check for markers of the disease. * Be asked to provide informed consent before beginning the study and agree to follow the study procedures, including having biopsies performed to analyze biomarkers before starting treatment. * Be followed for up to 2 years after completing the treatment to track their progress and response. This study aims to help doctors understand if Loncastuximab Tesirine can offer a new treatment option for patients who have not responded to CAR-T therapy and have limited options for further treatment. The trial will also provide more information on how to manage the safety of this treatment for these patients.

The goal of this clinical trial is to evaluate the effectiveness and safety of the anti-NKG2A monoclonal antibody (Monalizumab) in patients undergoing haploidentical stem cell transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PT-Cy). The main questions this trial aims to answer are: * Does Monalizumab improve graft-versus-host disease-free and progression-free survival (GPFS) in patients after Haplo-SCT? * What are the safety and side effects of Monalizumab in this patient group? * How does Monalizumab affect the reconstitution and function of NK cells in patients undergoing Haplo-SCT? * Researchers will administer Monalizumab to participants on day +30 and +44 after transplantation to see if it enhances immune responses and prevents disease relapse or GVHD. Participants will: * Receive Monalizumab intravenously at 1 mg/kg on day +30 and day +44 after Haplo-SCT * Be monitored for clinical outcomes such as GVHD, survival rates, and immune function for up to one year after the transplant * Undergo regular checkups and tests to assess the effectiveness and safety of the treatment

Inflammation during pregnancy represents an important risk factor for the development of neuropsychiatric disorders in the offspring. Despite clear epidemiological data supporting this association, translational studies aimed at identifying early predictive biomarkers and possible interventional strategies for this pathological condition are still missing. The MATERNALLY proposal aims to assess in a large patient cohort a novel multiparametric approach for the identification of predictive postnatal behavioral and circulating biomarkers. In parallel, a controlled mouse model for maternal immune activation will be exploited to understand the basic molecular mechanism that links inflammation with aberrant neural circuit formation and to unveil possible therapeutic targets. The integration of the two approaches will allow identifying early predictive biomarkers and proof of principle interventional strategies for this condition of high practical relevance to the neonatologist community