Wa?brzych, Poland

Diagnosis and Outcomes of Placental Accretism

Currently, the management of cases of placental accretism/percretism is not standardized. This study could help in assessing maternal and fetal outcomes related to the different therapeutic strategies applied in the clinical cases under study so that their management can be standardized in the near future. This is a retrospective and prospective, national multicenter study. Patients will be treated according to clinical practice. The main instrumental findings of cases of suspected accretism will be collected and analyzed, and the progression of pregnancy and postpartum (by means of laboratory and instrumental tests) will be evaluated in order to define the outcomes of conservative management (cesarean section with placenta in situ) versus more radical management (cesarean section and concomitant hysterectomy). In particular, clinical trends (by means of assessment of vital parameters, laboratory tests, ultrasound images or instrumental examinations) in pregnancy, in the immediate postoperative period and during subsequent outpatient follow-up visits will be analyzed. In general, in the absence of complications, visits will be performed twice a week during pre-partum. Postpartum follow-up is not standardized, as it will depend strictly on the procedure performed and the occurrence or absence of complications. There are no questionnaires and/or rating scales.

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.

Visceral Leishmaniasis in Emilia-Romagna (Leishmania-2019)

The term leishmaniasis refers to a heterogeneous group of anthropo-zoonoses caused by protozoa obligate intracellular protozoa, parasites of humans and various wild and domestic animals, belonging to the genus Leishmania. Despite being the cause of recurrent epidemic outbreaks with high rates of morbidity and mortality rates in certain geographical areas, the World Health Organisation (WHO) includes them among the Neglected Tropical Diseases. About 350 million people live in areas at risk for leishmaniasis with an estimated global prevalence of 12 million. The annual global incidence is estimated to be between 0.2 and 0.4 million cases for Visceral Leishmaniasis (LV) and between 0.7 and 1.2 million cases for Cutaneous Leishmaniasis Cutaneous. Leishmaniases are endemic infections in tropical, subtropical and temperate zones of all continents except Australia and Antarctica. More than 90% of LV cases are diagnosed in six countries: Bangladesh, Brazil, Ethiopia, India, South Sudan and Sudan, while the majority of LC cases are diagnosed in Afghanistan, Algeria, Brazil, Colombia, Iran, Pakistan, Peru, Saudi Arabia and Syria. Leishmaniasis is also endemic in the Mediterranean Basin, including Italy, and in this area about 5% of global cases are found there, with a clear prevalence of visceral forms. The incubation period varies from 4 to 10 months, but cases have been described in which incubation lasted for several years. The onset is mostly gradual and insidious and the most characteristic clinical manifestations are asthenia fever (often initially framed as FUO), night sweats, anorexia and weight loss, splenomegaly, hepatomegaly and lymphadenomegaly. From a laboratory point of view, characteristic are anaemia, leucopenia and thrombocytopenia, more or less associated with each other, up to full-blown pancytopenia. Dysprotidemia with hypergammaglobulinemia and hypoalbuminemia is typical. If not adequately treated, visceral leishmaniasis evolves towards a condition of cachexia and profound general decay and may prove fatal. A rare and serious complication of LV is the haemophagocytic syndrome. According to the 2010 WHO Leishmaniasis Control Report, a confirmed case of LV is defined as the association between typical clinical signs and symptoms (fever, splenomegaly, weight loss, etc.) and positivity of a parasitological examination (microscopy, RT-PCR or culture) in the presence or absence of positivity of serological investigations. The methods available for the diagnosis of LV include: - Serological tests: detection of Leishmania-specific IgG (or total Ig) in plasma or serum. enzyme immunoassay (EIA), indirect immunofluorescence assay (IFAT), immunochromatographic test (ICT) based on the immunochromatographic test (ICT) based on rK39 antigen, Western blot (WB). Disadvantages: these tests remain positive over time (it is not always possible to distinguish relapses); they may be positive in individuals with asymptomatic infection; they may be falsely negative in immunodepressed individuals (20-60% of cases). - Molecular biology tests: detection of Leishmania DNA by RT-PCR on peripheral blood bone marrow blood or any other material. Molecular tests are now considered the most sensitive methods sensitive for the diagnosis of LV and the accuracy in identifying Leishmania DNA is high for bone marrow aspirate and peripheral blood samples. RT-PCR should be performed in case the presence of suspicious symptoms and serological test positivity. However, in the presence of strong suspicion clinical suspicion or in immunocompromised patients, RT-PCR should also be performed in case of a negative serology test. Quantitative RT-PCR on peripheral blood may be useful in patients immunocompromised patients for monitoring parasitukaemia during therapy. Direct microscopic examination on bone marrow blood smear: sensitivity is variable (25-85%) and lower than the sensitivity of molecular methods. - Culture examination: culture isolation from bone marrow blood takes a long time (at least 4 weeks). Culture allows the isolation of the strain of Leishmania responsible for the disease and can also be can also be performed from biopsy tissue. According to reports in the literature, from 2012 to date, there has been an increase in the number of diagnosed cases of autochthonous visceral Leishmania in the Province of Bologna. In this context, it was decided to carry out a retrospective prospective observational study, which is essential to describe the epidemiology of LV in order to outline the scientific and rational bases necessary for the drafting of guidelines to standardise the diagnostic and therapeutic approach to this disease, in order to reduce the diagnostic delay and improve therapeutic results. therapeutic outcome. In addition, epidemiological data will make it possible to identify possible new strategies to control the disease, which are essential for reducing its transmission.

Integrative "Omics" Approaches for Leukemia Target Identification and Matched Therapeutic Intervention

Blue-green Space Physical Activity: the "Parco Del Mare" Study

The aim of the "Parco del Mare" pilot study is to evaluate the feasibility and the effects of a moderate-intensity exercise program carried out in a green-blue space, on health outcomes such as quality of life and physical performance. Healthy adults with no contraindication to practice physical activity will be recruited and divided into two groups: the experimental group involved in the exercise sessions performed twice a week for 6-months, while the control group received no intervention. Validated tests and questionnaires will be used to detect health parameters at baseline (T0) and follow-up (T1). The investigators expected the intervention carried out in the Parco del Mare setting to be feasible and effective in improving health parameters, quality of life and physical performance in healthy adults.

Ruxolitinib in Primary Myelofibrosis and Secondary to Essential Thrombocythemia or Polycythemia Vera

The study is observational multicenter retrospective and prospective cohort study of patients with primary or secondary myelofibrosis who have initiated therapy with ruxolitinib, prescribed as part of the normal course of care and completely independent of study participation. Laboratory tests and histological, cytogenetic, molecular, and radiological investigations performed by the patient and collected for study will be conducted in accordance with clinical practice, independent of the patient's participation in the study. In particular. data on systemic symptoms and splenomegaly will be collected at diagnosis and disease reassessments performed in the context of normal clinical practice. The minimum planned duration of individual patient observation is 3 months and the planned duration of the study is 10 years.

Multicentre Prospective Observational Study of Acute Intoxications in Paediatric Age

National Database of Bone Metastases

Epidemiological Study on Invasive Bacterial Diseases

Pathogen identification by culture methods has been shown to be unsatisfactory, as antibiotic therapy carried out in patients before hospitalization prevents bacterial culture development and subsequent typing in many cases. In addition, technical problems due to sample collection, storage and transport reduce germ viability leading to false negatives in pathogen identification by culture methods. In contrast, molecular diagnosis allows germ identification on biological samples even in the absence of germ viability, thus enabling more accurate diagnosis. Surveillance of infections caused by these pathogens and their distribution by serotypes/serogroups is essential to guide public health interventions, assess epidemiological trends, monitor any secondary cases, estimate the proportion of preventable cases, identify any vaccine failures, and evaluate the impact of vaccine strategies.In 2006, the AOU Meyer Immunology Laboratory received a grant from the National Center for Disease Prevention and Control (NCDC) to develop a molecular diagnostic method for surveillance of invasive infections with Neisseria meningitidis (meningococcal,) Streptococcus pneumoniae (pneumococcus) and Haemophilus influenzae (hemophilus) that would allow identification of the germ on biological samples even in the absence of germ viability, with a view to improving surveillance, prevention and treatment strategies. The project involved performing molecular diagnostic tests on samples from patients referred to hospitals in the Tuscany Region and outside the region. The present study aims to study the epidemiology of invasive bacterial diseases, characterize the circulating strains also in order to plan treatment and prevention strategies.

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.