Search

Background: A substantial number of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) experience adverse events after TAVI, with health care expenditure. We aimed to investigate cardiac remodeling and long-term outcomes in diabetic patients with severe AS, left ventricular ejection fraction (LVEF) < 50%, and extra-valvular cardiac damage (EVCD) undergoing TAVI treated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus other glucose-lowering strategies (no-SGLT2i users)., Methods: Multicenter international registry of consecutive diabetic patients with severe AS, LVEF < 50%, and EVCD undergoing TAVI. Based on glucose-lowering therapy at hospital discharge, patients were stratified in SGLT2i versus no-SGLT2i users. The primary endpoint was a composite of all-cause death and heart failure (HF)-hospitalization (major adverse cardiovascular events, MACE) at 2-year follow-up. Secondary outcomes included all-cause death, cardiovascular death, and HF hospitalization., Results: The study population included 311 patients, among which 24% were SGLT2i users. Within 1-year after TAVI, SGLT2i users experienced a higher rate of LV recovery (p = 0.032), especially those with baseline LVEF ≤ 30% (p = 0.026), despite the lower baseline LVEF. Patients not treated with SGLT2i were more likely to progress to a worse EVCD stage over time (p = 0.018). At 2-year follow-up, SGLT2i use was associated with a lower rate of MACE, all-cause death, and HF hospitalization (p < 0.01 for all). After adjusting for confounding factors, the use of SGLT2i emerged as an independent predictor of reduced MACE (HR = 0.45; 95% CI 0.17-0.75; p = 0.007), all-cause death (HR = 0.51; 95% CI 0.25-0.98; p = 0.042) and HF-hospitalization (HR = 0.40; 95% CI 0.27-0.62; p = 0.004)., Conclusions: In diabetic patients with severe AS, LVEF < 50%, and EVCD undergoing TAVI, the use of SGLT2i was associated with a more favorable cardiac remodeling and a reduced risk of MACE at 2-year follow-up., Competing Interests: Declarations. Ethics approval and consent to participate: Data were collected as part of an approved international multicenter observational study. The present study was conducted according to the principles of the Declaration of Helsinki; all patients were informed about their participation in the registry and provided informed consent for the anonymous publication of scientific data. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation., Methods: All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks., (© 2024. The Author(s).)

Background: The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents., Methods: In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels., Results: The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275-0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status., Conclusions: Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease., Trial Registration: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT., Clinicaltrials: gov Identifier: NCT05261867., (© 2022. The Author(s).)

Background: The prognostic role of hyperglycemia in patients with myocardial infarction and obstructive coronary arteries (MIOCA) is acknowledged, while data on non-obstructive coronary arteries (MINOCA) are still lacking. Recently, we demonstrated that admission stress-hyperglycemia (aHGL) was associated with a larger infarct size and inflammatory response in MIOCA, while no differences were observed in MINOCA. We aim to investigate the impact of aHGL on short and long-term outcomes in MIOCA and MINOCA patients., Methods: Multicenter, population-based, cohort study of the prospective registry, designed to evaluate the prognostic information of patients admitted with acute myocardial infarction to S. Orsola-Malpighi and Maggiore Hospitals of Bologna metropolitan area. Among 2704 patients enrolled from 2016 to 2020, 2431 patients were classified according to the presence of aHGL (defined as admission glucose level ≥ 140 mg/dL) and AMI phenotype (MIOCA/MINOCA): no-aHGL (n = 1321), aHGL (n = 877) in MIOCA and no-aHGL (n = 195), aHGL (n = 38) in MINOCA. Short-term outcomes included in-hospital death and arrhythmias. Long-term outcomes were all-cause and cardiovascular mortality., Results: aHGL was associated with a higher in-hospital arrhythmic burden in MINOCA and MIOCA, with increased in-hospital mortality only in MIOCA. After adjusting for age, gender, hypertension, Killip class and AMI phenotypes, aHGL predicted higher in-hospital mortality in non-diabetic (HR = 4.2; 95% CI 1.9-9.5, p = 0.001) and diabetic patients (HR = 3.5, 95% CI 1.5-8.2, p = 0.003). During long-term follow-up, aHGL was associated with 2-fold increased mortality in MIOCA and a 4-fold increase in MINOCA (p = 0.032 and p = 0.016). Kaplan Meier 3-year survival of non-hyperglycemic patients was greater than in aHGL patients for both groups. No differences in survival were found between hyperglycemic MIOCA and MINOCA patients. After adjusting for age, gender, hypertension, smoking, LVEF, STEMI/NSTEMI and AMI phenotypes (MIOCA/MINOCA), aHGL predicted higher long-term mortality., Conclusions: aHGL was identified as a strong predictor of adverse short- and long-term outcomes in both MIOCA and MINOCA, regardless of diabetes. aHGL should be considered a high-risk prognostic marker in all AMI patients, independently of the underlying coronary anatomy. Trial registration data were part of the ongoing observational study AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation. ClinicalTrials.gov Identifier: NCT03883711., (© 2021. The Author(s).)

Background: 22q11.2 deletion syndrome is one of the most common genomic disorders, characterized by the variable presence of facial dysmorphisms, congenital cardiac defects, velopharyngeal insufficiency/cleft palate, thymic hypoplasia/aplasia, immunodeficiency, parathyroid hypoplasia, developmental delay, learning disabilities, psychiatric disorders, renal, ocular, and skeletal malformations, hearing loss and laryngeal abnormalities. Chromosomal microarray (CMA) hybridization is one of the most performed diagnostic tests but as a genome wide analysis, it can point out relevant incidental copy number variations., Case Presentation: We report the case of a 2-year-old boy that came to our attention for mild psychomotor delay, poor growth, and minor facial anomalies. Considering a diagnosis of 22q11.2 deletion syndrome, we performed CMA that not only confirmed our diagnosis, but also pointed out an additional de novo 5q21.3q22.2 microdeletion, encompassing APC gene. As a result of the genetic testing we enrolled the patient in a tailored surveillance protocol that enabled the early detection of a hepatoblastoma. The child underwent surgical and chemotherapic treatments with complete cancer eradication., Conclusions: The concurrent finding of an expected result and an additional deletion of APC gene represents an example of a relevant issue about the health and ethical management of secondary findings revealed by genome-wide tests. Furthermore, this report highlights the need to develop dedicated surveillance guidelines for children with APC-related polyposis and raise the question whether to suspect and screen for APC-related conditions in cases of sporadic hepatoblastomas.

Background: Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA., Methods: Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF)., Results: The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients-obs-AMI and MINOCA-NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI (p < 0.001), a larger LVEDV (p = 0.003) and a lower LVEF (p < 0.001) compared to normoglycemic ones. Conversely, MINOCA patients showed a trivial myocardial damage, irrespective of admission glucose levels., Conclusions: Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.

Background: Rhabdomyosarcomas (RMSs) are the most frequent soft tissue sarcoma in children and adolescents, defined by skeletal muscle differentiation and the status of FOXO1 fusions. In pediatric malignancies, in particular RMS, scant and controversial observations are reported about PD-L1 expression as a putative biomarker and few immune checkpoint clinical trials are conducted., Methods: PD-L1 assessment was evaluated by immunohistochemistry (IHC) utilizing two anti-PDL1 antibodies, in a pilot cohort of 25 RMS. Results were confirmed in primary and commercial RMS cell lines by cytofluorimetric analysis and IHC., Results: PD-L1 expression was detectable, by both anti-PD-L1 antibodies, in the immune contexture of immune cells infiltrating and/or surrounding the tumor, in 15/25 (60%) RMS, while absent expression was observed in neoplastic cells. Flow cytometry analysis and PD-L1 IHC of commercial and primary RMS cell lines confirmed a very small percentage of PD-L1 positive-tumor cells, under the detection limits of conventional IHC. Interestingly, increased PD-L1 expression was observed in the immune contexture of 4 RMS cases post chemotherapy compared to their matched pre-treatment samples., Conclusion: Here we identify a peculiar pattern of PD-L1 expression in our RMS series with scanty positive-tumor cells detected by flow cytometry, and recurrent expression in the immune cells surrounding or infiltrating the tumor burden.