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The role of immunization in public health is crucial, offering widespread protection against infectious diseases and underpinning societal well-being. However, achieving optimal vaccination coverage is impeded by vaccine hesitancy, a significant challenge that necessitates comprehensive strategies to understand and mitigate its effects. We propose the integration of Population Health Management principles with Immunization Information Systems (IISs) to address vaccine hesitancy more effectively. Our approach leverages systematic health determinants analysis to identify at-risk populations and tailor interventions, thereby promoting vaccination coverage and public health responses. We call for the development of an enhanced version of the Italian National Vaccination Registry, which aims to facilitate real-time tracking of individuals' vaccination status while improving data accuracy and interoperability among healthcare systems. This registry is designed to overcome current barriers by ensuring robust data protection, addressing cultural and organizational challenges, and integrating behavioral insights to foster informed public health campaigns. Our proposal aligns with the Italian National Vaccination Prevention Plan 2023-2025 and emphasizes proactive, evidence-based strategies to increase vaccination uptake and contrast the spread of vaccine-preventable diseases. The ultimate goal is to establish a data-driven, ethically sound framework that enhances public health outcomes and addresses the complexities of vaccine hesitancy within the Italian context and beyond.

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/100 ml. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often owing to less medication adherence. In this prespecified subanalysis of the JET-Low Density Lipoprotein (JET-LDL) registry, we sought to evaluate the relation between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. The patients' self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-month follow-up. Depending on the score obtained, the population was divided into 2 groups: high adherence (HA, MMAS ≥6) versus low adherence (LA, MMAS <6). The occurrence of the primary end point (LDL-C reduction >50% from baseline or level <55 mg/100 ml at 1 month) was compared in the 2 groups. A total of 963 patients were included in the present analysis; in 277 cases (28.7%), an MMAS score <6 was reported (LA group), whereas in the remaining 686 (71.3%), the score obtained was ≥6 (HA group). No difference between the 2 groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1 month, the primary end point occurred in 62.5% of cases, with a statistically significant difference between the 2 groups (LA 60% vs HA 65%, p = 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary end point (odds ratio 0.48, 0.39 to 0.85, p = 0.006). In conclusion, in a real-world cohort of patients with ACS, less medication adherence to LLT was a common event (28.7%), negatively affecting LDL-C goal achievement., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Tethering is a common condition of the mitral valve apparatus in the presence of significant regurgitation. Its impact on outcomes of transcatheter edge-to-edge repair (TEER) remains poorly characterized., Methods: We appraised the prevalence, features, procedural details, and outcomes of patients with or without mitral valve tethering in a prospective multicenter observational study. The primary endpoint was the risk of cardiac death or rehospitalization for heart failure at mid-term follow-up., Results: We included 2238 patients, 1467 (65.5 %) without tethering and 771 (34.5 %) with tethering (487 [21.8 %] with symmetric and 284 [12.7 %] with asymmetric tethering). Several differences in baseline features were evident among groups, yet procedural results were similar. After a median of 14 months, rates of cardiac death or rehospitalization for heart failure was significantly higher at unadjusted analysis in patients with tethering (191 [24.8 %] vs. 272 [18.5 %] in those without tethering, p = 0.001), but weres similar between tethering subtypes (p = 0.666). At adjusted analysis, the presence of any tethering was no longer a significant predictor of cardiac death or rehospitalization for heart failure, and the same results were obtained focusing on tethering subtypes (all p > 0.05)., Conclusions: Tethering is common among patients with an indication to TEER, and is associated with adverse baseline and procedural features. In spite of this, device and procedural success rates are not significantly impacted by the presence of tethering that does not even have a negative prognostic effect at follow-up. Accordingly, tethering should not be considered a contraindication to TEER in suitable patients., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cancer progression is significantly influenced by the complex interactions within the tumor microenvironment (TME). Immune cells, in particular, play a critical role by infiltrating tumors from the circulation and surrounding lymphoid tissues in an attempt to control their spread. However, they often fail in this task. Current in vivo and in vitro preclinical models struggle to fully capture these intricate interactions affecting our ability to understand immune evasion and predict drugs behaviour in the clinic. To address this challenge, biofabrication and particularly 3D bioprinting has emerged as a promising tool for modeling both tumors and the immune system. Its ability to incorporate multiple cell types into 3D matrices, enable tissue compartmentalization with high spatial accuracy, and integrate vasculature makes it a valuable approach. Nevertheless, limited research has focused on capturing the complex tumor-immune interplay in vitro. This review highlights the composition and significance of the TME, the architecture and function of lymphoid tissues, and innovative approaches to modeling their interactions in vitro, while proposing the concept of an extended TME., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Here, we present a protocol for quantifying microglial cell morphology at the single-cell level in mice. We provide comprehensive details, starting from optimal mouse brain dissection to computational analyses of up to 350 microglial cells per brain slice. Analyzing the morphology of microglial cells is essential for understanding their functional and activation states in different conditions, including during disease development and progression, as well as for assessing the effect of therapeutic interventions. For complete details on the use and execution of this protocol, please refer to Lind-Holm Mogensen et al. 1 and Fixemer et al. 2 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Despite some evidence of a possible link between epileptogenesis and tumorigenesis in glioblastoma, the prognostic value of epilepsy at presentation has been debated over the years. We performed a systematic review and meta-analysis to summarize all published data evaluating the prognostic significance of seizures as a presenting manifestation of glioblastoma. A comprehensive search of five databases from inception to December 2023 was conducted. Included studies underwent meta-analysis, with subgroup analyses performed to identify sources of heterogeneity. Fifteen studies were included in the analysis. Seizures were considered a favorable prognostic factor in seven studies, while eight studies found no differences in overall survival between patients with seizures and those with other presenting symptoms. Eleven studies were included in the meta-analysis. The overall pooled analysis indicated a potentially favorable prognostic impact of seizures at the clinical onset of glioblastoma (HR 0.73; 95% CI 0.61-0.87). However, subgroup analysis within studies focusing on IDH-wild type cases showed no discernible impact from preoperative seizures. Retrospective design, poor quality in reporting results, and heterogeneity in tumor characteristics and therapies are the main limitations of included studies.Future prospective studies on large, homogeneous cohorts of patients with IDH-wild type glioblastoma are warranted. Overall, these findings suggest that while seizures may hold some prognostic value, further research is essential to clarify their role. Understanding the true prognostic role of seizures at clinical onset may enhance our ability to predict patient outcomes and guide clinical decision-making., Competing Interests: Declarations. Ethics approval: Not applicable (systematic review). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Consent to participate: Not applicable, as this study did not involve humans. Human ethics and consent to participate declarations: Not applicable., (© 2024. The Author(s).)

Background: The aim of this study was to analyze whether there are differences in performance indicators between matches played at different altitudes in professional padel., Methods: Data were collected and analyzed based on players' sex, set number, and set score using video footage from the World Padel Tour (WPT), including open-access TV broadcasts and WPT's YouTube channel. Performance indicators - such as break points won, errors, winners, and winning smashes - were recorded across 1122 sets (485 matches) from three WPT seasons (2020-2022)., Results: In men's padel, altitude-related differences were observed in break points (P=0.005), break points won (P=0.002), and winners (P=0.002). In women's padel, altitude-related differences were found in break points won (P=0.004), smashes (P<0.001), and winning smashes (P<0.001). Set number and set result were associated with variations in several performance indicators, depending on the tournament's altitude (below or above 500 meters)., Conclusions: These results represent reference data to help players and coaches train according to altitude conditions.

Cardiac implantable electronic device (CIED) infections are a highly morbid and potentially fatal complication of CIED implantation. Prompt diagnosis is paramount to the proper management of such infections. This review seeks to highlight the pathophysiology, risk factors, diagnostic approach, and prevention strategies for CIED infection, with an emphasis on pocket infection. Management will be discussed in detail, with complete device removal representing the standard of case, but with conservative management representing a potential alternative for patients at high risk for extraction. The high prevalence of CIED in the cardiac population renders understanding of this subject essential for the practicing clinician., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: We declare no competing interests.

Introduction: Neoadjuvant therapy (NAT) should increase the rate of breast-conserving surgery (BCS) in non-metastatic breast cancer (BC) patients, especially in those achieving tumor shrinkage. Still, the conversion from a pre-planned mastectomy to BCS in patients responding to NAT is not a widespread standard. We aimed to identify factors influencing surgical choices in this setting., Materials and Methods: We retrospectively collected data of BC patients with complete remission of primitive tumor (ypT0) after NAT, treated with BCS or mastectomy in two Italian breast units. Predictors of mastectomy were explored using logistic regression. Distant recurrence and event-free survival were assessed in the BCS and mastectomy cohort., Results: 243 patients were included, 147 (60.5 %) treated with BCS and 96 (39.5 %) treated with mastectomy. In the mastectomy group, there were more centrally-located, multiple and larger tumors. At univariate regression analysis, central location, baseline tumor extension on ultrasound (US) and magnetic resonance imaging (MRI), multiple foci and clinical stage were significantly associated with the chance of receiving mastectomy. At multivariate analysis, only baseline focality on US and extension on MRI retained significance as predictors of mastectomy. Distant recurrence and event-free survival were significantly longer in patients undergoing BCS., Conclusion: Baseline tumor extension and focality were the main predictors of mastectomy in patients with ypT0 after NAT. However, BCS did not negatively affect survival outcomes in our cohort. An effort should be made to avoid potentially unnecessary mastectomy in this population, aiming at minimizing surgery-associated toxicities and improving patients' quality of life., Competing Interests: Declaration of competing interest None, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

We aimed to assess the prevalence of and factors associated with Na + /K + imbalances in children hospitalized for febrile urinary tract infection (fUTI). This retrospective Italian multicenter study included children aged 18 years or younger (median age = 0.5 years) who were discharged with a primary diagnosis of fUTI. Na + /K + imbalances were classified as hyponatremia (sodium < 135 mEq/L), hypernatremia (sodium > 145 mEq/L), hypokalemia (potassium < 3.5 mEq/L), hyperkalemia (potassium > 5.5 mEq/L), and concurrent hyponatremia and hyperkalemia, in the absence of evidence of hemolyzed blood samples. Among the 849 enrolled children, 23% had hyponatremia, 6.4% had hyperkalemia, 2.9% had concurrent hyponatremia and hyperkalemia, 0.7% had hypokalemia, and 0.4% had hypernatremia. In the multiple logistic regression analysis, after applying the Bonferroni correction, only C-reactive protein (C-RP) levels were significantly associated with hyponatremia (OR = 1.04; 95% CI: 1.02-1.06; p < 0.001), only age was significantly associated with hyperkalemia (OR = 1.7; 95% CI: 1.1-2.7; p = 0.01), and only CAKUT was significantly associated with concurrent hyponatremia and hyperkalemia (OR = 4.3; 95% CI: 1.7-10.8; p = 0.002). Even after adjusting for the presence of kidney hypoplasia, abnormal renal echogenicity, pelvi-caliceal dilation, ureteral dilation, uroepithelial thickening of the renal pelvis, bladder abnormalities, pathogen other than E. coli, concurrent hyponatremia and hyperkalemia persisted significantly associated with CAKUT (OR = 3.6; 95% CI: 1.2-10.9; p = 0.02)., Conclusion: Hyponatremia was the most common Na + /K + imbalance in children hospitalized for fUTI, followed by hyperkalemia and concurrent hyponatremia and hyperkalemia. C-RP levels were most strongly associated with hyponatremia, age with hyperkalemia, and CAKUT with concurrent hyponatremia and hyperkalemia (suggestive of transient secondary pseudo-hypoaldosteronism). Therefore, in children who develop concurrent hyponatremia and hyperkalemia during the course of a fUTI, an underlying CAKUT could be suspected., What Is Known: • Na+ and K+ abnormalities can occur in patients hospitalized for febrile urinary tract infection (fUTI). • Concurrent hyponatremia and hyperkalemia during fUTI may suggest transient secondary pseudo-hypoaldosteronism (TPHA), for which limited data on prevalence are available., What Is New: • The most common Na+/K+ imbalance in children hospitalized with fUTI was hyponatremia (23%), followed by hyperkalemia (6.4%), concurrent hyponatremia and hyperkalemia (2.9%), hypokalemia (0.7%), and hypernatremia (0.4%). • Concurrent hyponatremia and hyperkalemia were mainly associated with CAKUT, while hyponatremia alone correlated with high C-reactive protein and hyperkalemia alone with younger age. In cases of concurrent hyponatremia and hyperkalemia during fUTI, an underlying CAKUT should be suspected., (© 2024. The Author(s).)

Objective: This study investigates the predictive role of indocyanine green angiography and thermography in assessing mastectomy skin flap necrosis in the intraoperative and postoperative setting., Methods: A retrospective review of 45 patients who underwent nipple-sparing mastectomy and immediate prepectoral reconstruction was performed. Mastectomy flap viability was evaluated intraoperatively with indocyanine green angiography and thermography after placement of an implant sizer and again postoperatively at 24 hours. Fluorescence pattern was analyzed with a near-infrared camera (IC-Flow TM Imaging System, Diagnostic Green GmbH, Germania) and thermographic images with FLIR ONE device. FLIR ONE and ICG images were then transposed on macroscopic breast images with a scale 1:1. The mastectomy skin flap was evaluated using the SKIN score (Mayo Clinic Classification)., Results: Overlap between angiography and thermography images was 87.95% intraoperatively and 95.95% 24 hours postoperatively. Overlay with mastectomy flap necrosis was higher in the intraoperative angiography group with statistical significance. Contrarily, such a difference was not apparent in the postoperative period., Conclusions: ICG appears to be a superior tool when used intraoperatively with fundamental implications on reconstructive decision-making, while thermography could be a valuable assessment method in the postoperative setting. Further studies are necessary to confirm such results and determine their clinical applicability., Competing Interests: Disclosure The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract: Beta-blockers are a crucial part of post-myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in patients with STEMI between 2012 and 2017 by comparing purchased tablets with expected ones at 1 year through pharmacy registries. Optimal adherence was defined as ≥80%. Primary outcomes included all-cause and cardiovascular death while secondary outcomes were MI, major/minor bleeding events, and ischemic stroke. The study included 4688 patients discharged on beta-blockers. The mean age was 64 ± 12.3 years, 76% were male, and the mean LVEF was 49.2 ± 8.8%. The mean adherence at 1 year was 87.1%. Optimal adherence was associated with lower all-cause (adjusted hazard ratio, 0.62, 95% confidence interval, 0.41-0.92, P : 0.02) and cardiovascular (adjusted hazards ratio, 0.55, 95% confidence interval, 0.26-0.98, P : 0.043) mortality. In patients with LVEF ≤40%, optimal adherence was linked to reduced all-cause and cardiovascular mortality, but this was not found in patients with either preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in patients with all-comers STEMI reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect was confirmed only in patients with reduced LVEF (<40%) at hospital discharge. Impact of adherence to beta-blockers in all-comers STEMI patients and according to LVEF at discharge: results from the real-world registry FAST-STEMI., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Biological therapies, such as mepolizumab, have transformed the treatment of severe eosinophilic asthma. Although mepolizumab's short-term effectiveness is established, there is limited evidence on its ability to achieve long-term clinical remission., Objective: To evaluate the long-term effectiveness and safety of mepolizumab, explore its potential to induce clinical and sustained remission, and identify baseline factors associated with the likelihood of achieving remission over 24 months., Methods: The REMIssion in Severe Eosinophilic Asthma Treated with Mepolizumab (REMI-M) is a retrospective, real-world, multicenter study that analyzed 303 patients with severe eosinophilic asthma who received mepolizumab. Clinical, demographic, and safety data were collected at baseline, 3, 6, 12, and 24 months. The most commonly used definitions of clinical remission, which included no exacerbations, no oral corticosteroid (OCS) use, and good asthma control with or without assessment of lung function parameters, were assessed. Sustained remission was defined as reaching clinical remission at 12 months and maintaining it until the end of the 24-month period., Results: Clinical remission rates ranged from 28.6% to 43.2% after 12 months and from 26.8% to 52.9% after 24 months based on the different remission definitions. The proportion of patients achieving sustained remission varied between 14.6% and 29%. Factors associated with the likelihood of achieving clinical remission included the presence of aspirin-exacerbated respiratory disease, better lung function at baseline, male sex, absence of anxiety/depression, gastroesophageal reflux disease, bronchiectasis, and reduced OCS consumption. Adverse events were infrequent., Conclusions: This study demonstrates the real-world effectiveness of mepolizumab in achieving clinical remission and sustained remission in severe eosinophilic asthma over 24 months. The identification of distinct factors associated with the likelihood of achieving clinical remission emphasizes the importance of comprehensive management of comorbidities and timely identification of patients who may benefit from biologics., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Glut-1 deficiency Syndrome (GLUT-1 DS) is a rare disease caused by a mutation in the SLC2A1 gene that codes for the glucose transporter protein GLUT-1 DS. Currently, there is no indicated drug therapy for this condition and ketogenic diet (KD) is the most effective remedy to treat it., Objective: The objective of this study was to review the published literature that evaluated the effectiveness of KD in the dietary management of GLUT-1 DS syndrome, describing the state-of-the-art the treatment pathway for patients with GLUT-1 DS syndrome in light of the current European regulatory framework within the National Health Services., Methods: The literature search was carried out on September 10, 2023, and all studies conducted in humans diagnosed with GLUT-1 deficiency syndrome and treated with KD were included., Results: A total of 156 scientific papers have been extracted. Applying the exclusion criteria, 38 articles have been considered eligible. In 29 out of 38 studies, the main outcome for determining the efficacy of KD was the measurement of the number of epileptic seizures, demonstrating that patients treated with KD experienced improvements with a clear reduction in the number of epileptic attacks. Currently, in the European Union, only one country provides full reimbursement by the national health system for KD., Discussion: Although they are crucial for the treatment of GLUT-1 DS, according with current food regulations, KD are not evaluated on the basis of an unambiguous efficacy result, but only on the basis of safety. As a result, it is desirable to carry out clinical studies in the coming years based on the determination of efficacy in target populations, also in view of the marketing of these products on the European market., Competing Interests: Consent for publication: The authors consent to the publication of the manuscript. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Studies evaluating the systematic use of cardiac computed tomography (CCT) for the preprocedural assessment of myocardial fibrosis are limited. Their implementation in the electrophysiology workflow has not been extensively described., Objective: This study aimed to explore the degree of concordance between CCT and electroanatomic mapping (EAM) for the evaluation of cardiac fibrosis in patients undergoing endo-epicardial ventricular tachycardia (VT) ablation., Methods: From November 2017 to December 2021, patients undergoing endo-epicardial VT catheter ablation with CCT as the only source of preprocedural scar assessment were prospectively enrolled. After image integration, myocardial fibrosis detected with CCT was compared with low-voltage areas identified by endo-epicardial EAM. Postprocedural VT recurrences of this approach were evaluated after at least 1 year of follow-up., Results: The study enrolled 35 patients (mean age, 60.7 ± 13.2 years; 94.2% male). The most common underlying arrhythmic substrate was dilated cardiomyopathy (48.6%). CCT was employed for contraindications to cardiac magnetic resonance, such as unstable VTs (31.4%) or nonconditional implantable cardioverter-defibrillators (28.6%), but also for patients' and operators' preferences (14.3%-25.7%). Myocardial fibrosis was correctly identified by CCT and EAM, with strong agreement between these techniques both overall (Cohen κ for agreement, 0.933) and in per-segment analysis (κ ranging from 0.796 to 1.0). Ischemic patients showed the best correlation (κ = 1.000), whereas myocarditis showed the worst (κ = 0.750). After a median follow-up of 14 (12-24) months, 1-year freedom from recurrences was achieved in 74.3% patients; overall freedom from recurrences was 60.0%., Conclusion: A CCT-based preprocedural assessment before VT ablation is feasible, showing high diagnostic concordance with EAM in detecting myocardial fibrosis., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The current knowledge about the role of comorbidities in systemic sclerosis (SSc) is limited. Therefore, the aim of this study was to evaluate the prevalence of comorbidities and their impact on disease activity and prognosis in the Systemic sclerosis PRogression INvestiGation (SPRING) registry., Methods: SSc patients from the SPRING registry, fulfilling the ACR/EULAR 2013 classification criteria, with complete data on baseline comorbidities were enrolled. The Charlson comorbidity index (CCI) was used to quantify the overall comorbidity burden. The disease activity was calculated using the revised EUSTAR activity index (AI). The impact of SSc features on CCI, the effect of CCI on SSc disease activity and mortality were tested with multivariable regression models., Results: Among 1910 SSc patients enrolled, 67.3 % had at least one comorbidity at baseline. The most frequent comorbidities were systemic arterial hypertension (23.7 %), osteoporosis (12.9 %) and dyslipidemia (11 %). The mean value of CCI score was 2.0 ± 1.8. When patients were grouped according to increasing levels of CCI, a clear separation in the distribution of SSc-related clinical features could be observed. Among over 900 patients with available follow-up, no association between baseline CCI and changes in disease activity was observed. Conversely, the risk of death over time was independently predicted by both CCI and AI., Conclusions: Comorbidities and disease activity independently impact on the prognosis of SSc patients. This suggests that the management of comorbidities, together with the reduction of disease activity, is fundamental to improve patient survival., Competing Interests: Declaration of competing interest Orlandi M, Bellando-Randone S, Ferri C, Foti R, Codullo V, De Angelis R, Cuomo G, Campochiaro C, Luca Magnani, Cacciapaglia F, Ariani A, Giuggioli D, and Guiducci S have no conflict of interest to declare. Matucci-Cerinic M received fees from Actelion, Janssen, Inventiva, Bayer, Biogen, Boehringer, CSL Behring, Corbus, Galapagos, Mitsubishi, Samsung, Regeneron, Acceleron, MSD, Chemomab, Lilly, Pfizer, Roche. Bruni C received consulting fees and/or honoraria from Eli-Lilly, Boehringer Ingelheim, Research grants from Gruppo Italiano Lotta alla Sclerodermia (GILS), European Scleroderma Trials and Research Group (EUSTAR), Scleroderma Clinical Trials Consortium (SCTC), Scleroderma Research Foundation (SRF), Novartis foundation for biomedical research. Congress supports from Boehringer-Ingelheim. Educational grants from AbbVie and Wellcome Trust., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The basilar artery is one of the two cases in our body where an arterial vessel is formed by the union of two others - the vertebral arteries. It provides vascular supply to essential structures for the main vital functions; the posterior cerebral arteries originate from it as terminal branches, and form part of the anastomotic circle of Willis., Imaging Findings: Congenital and acquired anomalies of the basilar trunk are described. We provide a schematic and detailed representation of normal anatomical variants - mainly represented by the fenestrated basilar artery or the persistence of carotid-basilar anastomosis; course anomalies are also illustrated, with reference to neuro-vascular conflicts and dolichoectasia. Among congenital anomalies, this pictorial review also shows the variants of the basilar origin, such as in the case of basilar trunk arising from only one of the two vertebral arteries, and the calibre changes - which are represented by aneurysm and hypoplasia. The latter appears to be a risk factor for posterior circulation stroke, when associated with a bilateral posterior foetal variant.Among the acquired forms, this pictorial essay describes some clinical cases of dissections, non-congenital aneurysms, thrombosis and tumour with vascular encasing or compression of basilar artery., Conclusion: CT angiography and MRI allow us to study the posterior intracranial circulation in detail, providing useful pre-treatment information. Therefore, knowledge of congenital or acquired anomalies of the basilar artery is essential for radiologists, neuroradiologists and neurosurgeons., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: “Conflict of Interest - State: - Stefano Palmucci received personal consulting fees and/or speaker fees from Boehringer Ingelheim, F. Hoffmann La Roche Ltd, Elma Research srl, DOT Tech srl; he received personal honorarium for trainer of Respiratory Endpoints Study from Metanoic Health Ltd; he also received traveling support and accomodation from Bracco Imaging, Bayer Schering and ECLAT srl. All mentioned relationships are not related to this submitted manuscript.”

Background: Head-to-head comparisons of second and third generations of THVs are mostly limited to two-arm studies, and to mid-term follow-up so far. Aim of the study was to simultaneously compare clinical outcomes of transcatheter aortic valve replacement (TAVR) with four different transcatheter heart valves (THVs) at 5 years., Methods: Patients undergoing transfemoral TAVR with four second-generation THV platforms and enrolled in the multicenter, prospective OBSERVANT II study from December 2016 to September 2018, were compared according to the THV received. Outcomes were adjudicated through a linkage with administrative databases and adjusted using inverse propensity of treatment weighting (IPTW) based on propensity score. The primary endpoints were death from any cause and major adverse cardiac and cerebrovascular events (MACCE) at 5 years. Cumulative rates were reported consecutively for Evolut R/ PRO, SAPIEN 3, ACURATE neo and Portico groups., Results: A total of 2,493 patients were considered. The median age was 83 years and the median EuroSCORE 2 was 4.9%. After IPTW adjustment, the rates of all-cause death (53.6% vs. 46.7% vs. 50.5% vs. 46.3%, p=0.06) and MACCE (57.2% vs. 51.2% vs. 54.4% vs. 50.6%, p=0.08) did not differ among groups at 5 years. The rate of re-hospitalization for heart failure (HF) (33.9% vs. 27.0% vs. 31.6% vs. 33.7%, p=0.02) was significantly lower for SAPIEN 3 THV at 5 years., Conclusions: Data from real-world practice showed sustained and comparable effectiveness of TAVR considering all the available THVs up to 5 years, but SAPIEN 3 showed a lower rate of rehospitalization for HF., (Copyright © 2024. Published by Elsevier Inc.)

Fluoroquinolone-resistance in Shigella is among the serious antimicrobial resistance (AMR) threats. We investigated the genomic epidemiology of fluoroquinolone resistant (FQR) strains of S. sonnei and S. flexneri from 2015 to 2022 in Spain and Portugal. We determined the AMR profiles of 416 isolates (S. flexneri and S. sonnei) and FQR isolates were subjected to whole-genome sequencing. The percentage of FQR isolates gradually increased to reach 38% and 80% of S. flexneri and S. sonnei isolates, respectively in 2022. S. sonnei isolates from men were significantly more likely to be FQR (RR = 4.9, 95% CI = 2.7- 9.0). Genomic analysis revealed two major genetic clusters of FQR S. sonnei from the CipR.MSM5 lineage, previously associated with extreme antimicrobial resistance and transmission in men having sex with men. This study contributes to a better understanding of FQR shigellosis transmission and highlights the added value of enhanced surveillance for these pathogens., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Pancreatic cancer, with its increasing incidence and lowest 5-year survival rate, is predicted to become the second leading cause of cancer deaths by 2030. Current clinical trials have shown limited improvement, highlighting the need for new therapies. The sigma-2 receptor (S2R), with roles in tumor progression, is a target for novel thiosemicarbazones (TSCs). FA4 has shown potent activity against pancreatic cancer in vivo . We synthesized complexes of FA4 with Cu(II) and Pt(II), and compared their efficacy with complexes of the non-S2R-targeting TSC 1 . TSC-Cu exhibited over 50-fold higher in vitro cytotoxicity than TSCs-Pt, which was less active than TSCs. FA4 -Cu induced apoptotic cell death via ER and mitochondrial stress showing more potent activity than FA4 . This in vitro effect was replicated in the preclinical PANC-1 model, where FA4 -Cu was more potent than FA4 , 1 , and 1 -Cu. These results support further exploration of FA4 -Cu as a potential therapy for pancreatic cancer.

Background: The Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD™) questionnaire is a reliable indirect indicator of functional, health status and quality of life in children with severe Cerebral Palsy (CP), as well as the caregiving burden. The aim of the study is to validate the Italian translation of Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD™) questionnaire and assess its reliability and validity., Methods: A cross-sectional study was conducted. The study involved 60 caregivers of children with CP, classified according to the Gross Motor Function Classification System (GMFCS) levels I-V. There was a self-compilation of the CPCHILD™ by primary caregivers during the clinical visit and a re-administration of the questionnaire 2-3 weeks after the first to a defined sample (N.=30, GMFCS IV-V). The Italian version of CPCHILD™'s psychometric properties were evaluated through internal consistency, test-retest reliability, and validity analyses., Results: The translated CPCHILD™ questionnaire showed excellent test-retest reliability (Intraclass Correlation Coefficient - ICC=0.97) across most sections, with significant construct validity, differentiating well between the various GMFCS levels. The internal consistency was robust (Cronbach's alpha=0.852) except for the health section. The face validity indicated high relevance of the questionnaire items to the caregivers, particularly in emotional well-being and social interaction., Conclusions: The Italian version of CPCHILD™ questionnaire is a reliable and valid tool for assessing the quality of life in children with severe CP, offering insights into the care burden and health status impacts perceived by caregivers.

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of psychotherapeutic interventions in the treatment of older adults with depression and whether the effects of different types of psychotherapeutic treatments vary for older adults with depression., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Sleep-disordered breathing is common in stroke and may negatively affect its outcome. Screening for sleep-disordered breathing in this setting is of interest but poorly studied. We aimed to evaluate the performance of eight obstructive sleep apnea screening questionnaires to predict sleep-disordered breathing in acute stroke or transient ischaemic attack patients, and to assess the impact of stroke/transient ischaemic attack-specific factors on sleep-disordered breathing prediction. We analysed acute stroke/transient ischaemic attack patients (N = 195) from a prospective cohort ("Sleep Deficiency and Stroke Outcome study"). Assessments included anthropometrics, stroke-specific parameters, sleep history, an in-hospital respiratory polygraphy within the first week after stroke, and obstructive sleep apnea screening questionnaires (Berlin Questionnaire, Epworth Sleepiness Scale, STOP-BANG, NoSAS, Sleep Apnea Clinical Score, No-Apnea, Sleep Obstructive apnea score optimized for Stroke, SLEEP-IN). In a binary classification task for respiratory event index ≥ 15 per hr, we evaluated the performance of the above-mentioned questionnaires. We used logistic regression to identify predictors for sleep-disordered breathing in this cohort. The areas under the curve for respiratory event index ≥ 15 per hr were: Berlin Questionnaire 0.60; STOP-BANG 0.72; NoSAS 0.69; No-Apnea 0.69; Sleep Apnea Clinical Score 0.75; Epworth Sleepiness Scale 0.50; Sleep Obstructive apnea score optimized for Stroke 0.58; and SLEEP-IN 0.67. The No-Apnea had the lowest false omission rate (0.13), a sensitivity of 0.97 and a specificity of 0.12. In multiple logistic regression analysis (respiratory event index ≥ 15 per hr), age, neck circumference, National Institutes of Health Stroke Scale at admission, prior stroke, cardioembolic stroke aetiology and observed apneas were associated with sleep-disordered breathing. The logistic regression model performed similar (area under the curve 0.80) to Sleep Apnea Clinical Score (p = 0.402) and STOP-BANG (p = 0.127), but outperformed the other questionnaires. Neither existing questionnaires nor our statistical model are sufficient to accurately diagnose sleep-disordered breathing after stroke, thus requiring sleep study evaluation. The No-Apnea questionnaire may help to identify patients amenable to sleep testing., (© 2024 European Sleep Research Society.)

We appraise other people's emotions by combining multiple sources of information, including somatic facial/body reactions and the surrounding context. A wealthy literature revealed how people take into account contextual information in the interpretation of facial expressions, but the mechanisms mediating such influence still need to be duly investigated. Across two experiments, we mapped the neural representations of distinct (but comparably unpleasant) negative states, pain and disgust, as conveyed by naturalistic facial expressions or contextual sentences. Negative expressions led to shared activity in fusiform gyrus and superior temporal sulcus. Instead, pain contexts recruited supramarginal, postcentral and insular cortex, whereas disgust contexts triggered the temporo-parietal cortex and hippocampus/amygdala. When pairing the two sources of information together, we found higher likelihood of classifying an expression according to the sentence preceding it. Furthermore, networks specifically involved in processing contexts were re-enacted whenever a face followed said context. Finally, the perigenual medial prefrontal cortex showed increased activity for consistent ( vs inconsistent) face-contexts pairings, suggesting that it integrates state-specific information from the two sources. Overall, our study reveals the heterogeneous nature of face-context information integration, which operates both according to a state-general and state-specific principle, with the latter mediated by the perigenual medial prefrontal cortex. Significance Statement With the aid of controlled database and a comprehensive paradigm, our study provides new insights of the brain and behavioral processes mediating contextual influences on face emotion-specific processing. Our results reveal that context operates both in face-independent and face-conditional fashion, by biasing the interpretation of any face towards the state implied by associated context, and also triggering processes that monitor the consistency between the different sources of information. Overall, our study unveils key neural processes underlying the coding of state-specific information from both face and context and sheds new light on how they are integrated within the medial prefrontal cortex., (Copyright © 2024 the authors.)

Background: Prosthesis-patient mismatch after transcatheter aortic valve replacement (TAVR) can be measured echocardiographically (measured prosthesis-patient mismatch [PPMm]) or predicted (predicted prosthesis-patient mismatch [PPMp]) using published effective orifice area (EOA) reference values. However, the clinical implications of PPM post-TAVR remain unclear., Objectives: This study aimed to elucidate the prevalence of PPMm and PPMp post-TAVR and their impact on mortality in a large international cohort., Methods: The IMPPACT TAVR (Impact of Measured or Predicted Prosthesis-pAtient mismatCh after TAVR) registry included 38,808 TAVR patients from 26 international centers. Valve Academic Research Consortium 3 criteria were used to define prosthesis-patient mismatch severity. EOA was determined echocardiographically (PPMm) or predicted (PPMp) based on core lab-derived EOA reference values. The primary endpoint was 2-year all-cause mortality., Results: The prevalence of PPMp (moderate: 6.8%, severe: 0.6%) was significantly lower than that of PPMm (moderate: 20.7%, severe: 4.3%; P < 0.001) with negligible correlation between the 2 methods (Kendall's tau c correlation coefficient: 0.063; P < 0.001). In unadjusted analyses, severe PPMm adversely influenced 2-year survival (HR: 1.22; 95% CI: 1.02-1.45; P = 0.027), whereas severe PPMp was not associated with outcomes (HR: 0.81; 95% CI: 0.55-1.19; P = 0.291). After adjusting for confounders, neither PPMm nor PPMp had a significant effect on 2-year all-cause mortality., Conclusions: PPMm and PPMp were associated with different patient characteristics, with PPMm tending toward worse (especially low flow) and PPMp toward better (especially women) survival. After adjusting for confounders, neither PPMm nor PPMp significantly affected 2-year all-cause mortality. Hence, valve selection should not solely be based on hemodynamics but rather on a holistic approach, including patient and procedural specifics., Competing Interests: Funding Support and Author Disclosures This work was supported by the Deutsche Forschungsgemeinschaft (397484323) to Drs Guthoff, Matti Adam and Stephan Baldus, and Mauri; PA 2409/5-2 to Drs Thurow and Pauly; the Dean’s Office, Faculty of Medicine, University of Cologne (clinician scientist position) to Dr Guthoff; and the Center for Molecular Medicine Cologne (Baldus B-02) to Dr Stephan Baldus. Dr Abdel-Wahab’s institution has received speaker honoraria and/or consultancy fees from Abbott, Boston Scientific, and Medtronic. Dr Kim has received proctor and personal fees from Abbott, Boston Scientific, Meril Life Sciences, and Shockwave Med; is a member of the advisory boards for Abbott, Boston Scientific, and HID Imaging; and Dr Kim’s institution has received fees from Boston Scientific. Dr Nombela-Franco has served as proctor for Abbott and Edwards Lifesciences. Dr Matjaz Bunc served as proctor for TAVR procedures with Edwards Lifesciences, Medtronic, Meril, and Abbott. Matjaz Bunc is a member of the advisory boards for Medtronic and Edwards Lifesciences. Dr Veulemans has received speaker and/or study honoraria from Edwards Lifesciences, Medtronic, and Boston Scientific. Dr Tanja Rudolph has received lecture fees from Abbott, SIS Medical and Translumina. Dr Zeus has received speaker and/or study honoraria from Edwards Lifesciences, Medtronic, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background Giant intracranial aneurysms (GIAs) require complex treatment strategies including clipping, coiling, stenting, parent artery occlusion, bypass, or combined procedures. Neurovascular hybrid operating rooms (h-OR) combine a conventional operating theatre with high-resolution digital subtraction angiography (DSA). We describe a one-step combined surgical and endovascular treatment in a h-OR for a paediatric internal carotid artery giant aneurysm that can be an optimal solution to manage challenging cases, such as giant aneurysms. Case Description An 11-year-old boy presented with rapid onset right hemiparesis and left eyelid ptosis. A three months history of headache associated with sporadic vomit was reported. A giant, unruptured, left internal carotid artery aneurysm (ICA) was detected on imaging. The patient underwent surgical trapping of the aneurysm. Intraoperative DSA showed residual backflow from the posterior communicating artery (PComA) and coils were placed to completely exclude the aneurysm. At 18 months follow up, the patient showed a complete recovery and MRI showed a progressive reduction of the sac aneurysm. Conclusions Due to their morphologic variability, intracranial giant aneurysms may require a different procedural strategy instead of direct clipping or coiling. The introduction of h-OR allows combined treatments to be performed simultaneously in the same room setting. The present case shows that combined treatment in a neurovascular h-OR can be an optimal solution to manage challenging cases, such as giant aneurysms, reducing operative time with the added benefit of selecting an appropriate strategy adjustment in a multidisciplinary effort., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorders (PCSM-LPDs), represent a rare group of haematological diseases primarily affecting the skin. In this retrospective single-centre case series study, we aimed to investigate the demographic, clinical, therapeutic and prognostic aspects of PCSM-LPD. We collected data from cases diagnosed between 2010 and the present, employing histopathological and immunohistochemical methods following the World Health Organization criteria. We included 22 patients with a median age of 61.5 years and a median time between clinical onset and diagnosis of 3.0 months. Surgical excision with conservative margins was the primary choice, showing clinical remission in 17 cases, while nonsurgical treatments, including radiotherapy, high-potency steroids and ablative laser, achieved clinical remission in four cases. Clinical presentations varied, but the most common was a single violaceous nodule or papule on the upper body parts. In conclusion, our single-centre case series provides valuable insights into PCSM-LPD, highlighting the effectiveness of surgical treatments and the potential of nonsurgical ones. Even if controversial, the benign nature of PCSM-LPD emphasizes the importance of achieving tumour clearance with acceptable aesthetic outcomes., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: New conduction disturbances are frequent after transcatheter aortic valve implantation (TAVI). Refining our ability to predict high-grade atrioventricular block (AVB) occurring later than 24 hours after the procedure would be useful in order to select patients eligible for early discharge., Aims: This study was designed to identify predictors of high-grade AVB occurring between 24 hours and 30 days after TAVI and to develop and validate a predictive risk score., Methods: We analysed clinical, procedural, and electrocardiographic parameters of 1,290 TAVI patients. Independent predictors of delayed high-grade AVB were used to develop the predictive score, which was then externally validated in a cohort of 936 patients., Results: Implantation of self-expanding valves, greater implantation depth, longer PR interval in preprocedural electrocardiogram (ECG) and greater increase of PR duration in next-day ECG, preprocedural right bundle branch block (RBBB) and new-onset left bundle branch block or RBBB that persisted in next-day ECG were independent predictors of delayed high-grade AVB and were combined to develop the Delayed atrioventricular block Prediction for eArly disChargE (D-PACE) score. The areas under the curve of the score were 0.879 (95% confidence interval [CI]: 0.835-0.923) and 0.799 (95% CI: 0.730-0.868) in the derivation and validation cohorts, respectively. Based on the score, patients can be classified into three risk categories; low-risk patients demonstrated an incidence of delayed AVB of less than 1% and are ideal candidates for next-day discharge., Conclusions: The D-PACE score can be used to stratify TAVI patients according to their risk of delayed high-grade AVB and thereby identify those suitable for next-day discharge.

Background: Transanal excision of rectal cancer can be considered the definitive surgical treatment if the depth spread is T1 or lower, and the lesion is completely included within the resection margin. This study aims to analyze the immune microenvironment in healthy rectal mucosa as a possible predictor of tumor infiltration depth, lateral tumor spread, and recurrence of rectal cancer after transanal local excision., Methods: This study is a subanalysis of data from the IMMUNOREACT 1 and 2 trials (NCT04915326 and NCT04917263, respectively) including all the patients who underwent transanal excision of rectal cancer. This multicentric study collected healthy mucosa surrounding the neoplasms of patients with rectal cancer. A panel of immune markers was investigated at immunohistochemistry: CD3, CD4, CD8, CD8β, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Flow cytometry determined the proportion of epithelial cells expressing CD80, CD86, CD40, HLA ABC or HLA DR and the proportion of activated CD8+ T cells, CD4+ Th1 cells, and Treg., Results: Receiver operating characteristic curve analysis for predicting deep tumor spread showed an area under the curve of 0.70 (95% confidence interval: 0.60-0.80) for CD25+FoxP3+ cell rate and 0.74 (95% confidence interval: 0.53-0.92) for CK+CD86+ cell rate. Receiver operating characteristic curve analysis for predicting lateral tumor spread showed an area under the curve of 0.82 (95% confidence interval: 0.61-0.99) for CD8+CD38+ MFI, 0.96 (95% confidence interval: 0.85-0.99) for CD8β infiltration, and 0.97 (95% confidence interval: 0.87-0.99) for CK+HLAabc+ cell rate. Receiver operating characteristic curve analysis for predicting recurrence showed an area under the curve of 0.93 (95% confidence interval: 0.76-0.99) for CD8+CD38+ MFI and 0.94 (95% confidence interval: 0.78-0.99) for CD8+CD28+ MFI. Low CD8+CD38+ MFI and low CD8+CD28+ MFI were associated with shorter disease-free survival (P = .025 and P = .021, respectively)., Conclusion: Our study showed that the association between the high proportion of epithelial cells acting as presenting cells and deep or lateral tumor spread may be explained by the presence of a greater tumor load at the site. Moreover, it showed that weak activation of CD8+ T cells within the rectal mucosa is associated with lateral tumor spread and eventually a higher recurrence rate. The mucosal level of CD8β infiltration detected at immunohistochemistry might be tested as a marker of lateral tumor spread and potentially translated into clinical practice., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We previously demonstrated that patients with metastatic unresectable stage IIIb-IV melanoma receiving cetirizine (a second-generation H1 antagonist antihistamine) premedication with immunotherapy had better outcomes than those not receiving cetirizine. In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). Transcriptomic analysis showed that inducible T cell costimulator ligand (ICOSLG) expression directly correlated with the disease control rate (DCR) when detected with a loading value > 0.3. A multivariable logistic regression model showed a positive association between the DCR and ICOSLG expression for progression-free survival and overall survival. ICOSLG expression was associated with CD64, a specific marker of M1 macrophages, at baseline in the patient samples who received cetirizine concomitantly with checkpoint inhibitors, but this association was not present in subjects who had not received cetirizine. In conclusion, our results show that the clinical advantage of concomitant treatment with cetirizine during checkpoint inhibition in patients with malignant melanoma is associated with high ICOSLG expression, which could predict the response to immune checkpoint inhibitor blockade.

Background: Serous tubal intraepithelial carcinoma (STIC) is an early-stage cancerous lesion found in the fallopian tubes, often at the fimbrial end. It is strongly associated with high-grade serous carcinoma (HGSC), a highly aggressive type of ovarian cancer. STIC is considered a precursor to many HGSC cases, originating in the fallopian tubes. Its development is frequently linked to mutations in the TP53 gene, leading to the formation of a p53 signature, an early abnormality that may progress to HGSC. This signature is more common in BRCA mutation carriers, explaining the higher incidence of STIC in this group. The aim of this review is to evaluate the literature on the incidence of serous tubal intraepithelial carcinoma in patients (both BRCA-positive and BRCA-negative) undergoing preventive salpingo-oophorectomy, analysing the available data and identifying associations between specific characteristics and the onset of STIC., Methods: A comprehensive review of the literature from 2016 to 2023 was conducted using PubMed, focusing on studies analysing the incidence of STIC in BRCA-positive patients undergoing preventive salpingo-oophorectomy. Data on patient characteristics, interventions, outcomes, and incidence of STIC were extracted and analysed., Results: Nine international studies were included in the review, reporting varying incidences of STIC among patients undergoing salpingo-oophorectomy. The overall incidence of STIC in all the women included in the studies was 7.31%, while that in the BRCA-mutated women was approximately 6.08%. Notably, the presence of the TP53 signature was significantly associated with the occurrence of STIC., Conclusions: The etiopathogenesis of STIC involves complex interactions between genetic, environmental, and molecular factors. Further research is needed to fully understand its mechanisms and identify additional risk factors beyond BRCA mutations. Establishing a national database of STIC cases could facilitate future research and improve patient outcomes.

Objective: To evaluate the cardiac involvement in patients with Still's disease with a focus on myocarditis included in the multicenter AIDA (AutoInflammatory Disease Alliance) network Still's disease registry. To exploit the predictive factors for myocarditis in deriving a clinical risk patient profile for this severe manifestation., Methods: A multicenter observational study was built up assessing consecutive patients with Still's disease characterized by the cardiac involvement among those included in the AIDA Network Still's Disease Registry. The cardiac involvement was defined according to the presence of pericarditis, tamponade, myocarditis, and/or aseptic endocarditis., Results: In total, 73 patients with Still's disease and cardiac involvement were assessed (mean age 36.3±19.9 years, 42.5% male sex); out of them, 21.9% were children. The most common cardiac manifestation was the pericarditis in 90.4% of patients, 26.0% presented with myocarditis, and less frequently endocarditis (2.7%) and tamponade (1.4%). Comparing clinical features of patients with myocarditis than others, significantly increased frequencies of skin rash, and pleuritis as well as higher values of systemic score were recognised. Furthermore, an enhanced mortality rate was registered in patients with myocarditis. In regression models, the skin rash and the systemic score independently predicted the myocarditis., Conclusion: The characteristics of patients with Still's disease and cardiac involvement were assessed in the AIDA network. The most common feature was the pericarditis but also a more severe clinical picture was reported in patients with myocarditis. The latter was associated with increased mortality rate and with higher systemic score, identifying patients to be carefully managed.

Purpose: In this study, we investigated whether experimental knee pain alters lower limb kinematics and knee arthrokinematics during gait, and if this motor adaptation depends on the spatial characteristics of the painful stimulus., Methods: Twenty-one participants walked on a treadmill for 60-s trials, either without stimulation or while experiencing painful electrical stimulation in the medial, lateral or anterior region of the knee. Perceived pain location was analyzed using pain drawing. Gait spatiotemporal parameters, lower limb kinematics, and dispersion of the knee helical axes on the sagittal plane were quantified for each trial and compared between conditions using ANOVAs with repeated measures or Friedman tests., Results: Pain perception was localized in the area the stimulation was applied to. Compared to walking without pain, participants demonstrated reduced knee extension (1.5 ± 1.5 degrees, p = 0.002) and reduced hip extension (0.8 ± 1.1 degrees, p = 0.037) when pain was induced in the anterior region, but not medially or laterally. Anterior knee pain increased the mean distance of the helical axes during late stance (0.7 [0.3, 1.4], p = 0.010), while medial pain increased both mean distance (0.3 [0.1, 0.5], p = 0.037) and mean angle (1.2 ± 1.4, p = 0.010) during early swing., Conclusion: Acute, experimental knee pain alters gait kinematics and increases the dispersion of the helical axis. These adaptations depend on the spatial characteristics of the painful stimulus. These adaptations may reflect an attempt of the central nervous system to protect the painful tissue while searching for a less painful movement strategy., Competing Interests: Declarations Conflict of interest The authors declare no competing interests or conflicts of interest., (© 2024. The Author(s).)

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) is a haemato-inflammatory syndrome genetically defined by somatic mutations in the X-linked UBA1 gene, typically Val/Thr/Leu substitutions at the Met41 hotspot. Clinical manifestations are heterogeneous and refractory to most haemato-rheumatological treatments. To date, no guidelines exist for the management of VEXAS, and scarce is the evidence on methodology and clinical significance of longitudinal UBA1 clonal burden evaluation upon therapy. Here, we validated a method to quantify UBA1 clonal burden and explored its applicability in patients with VEXAS. Given the different treatment interactions, droplet digital polymerase chain reaction (ddPCR) may allow for informed therapeutic decisions and implementation of personalized strategies., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Urinary tract infections (UTIs) are common bacterial infections in children. UTIs may be limited to the bladder or involve the kidneys with possible irreversible damage. Congenital abnormalities of the kidney and urinary tract (CAKUT) are often associated with UTIs; kidney scars have been considered a consequence of untreated UTIs but may be congenital. The mechanism by which bacteria produce inflammation in the urinary system has been intensively investigated. Diagnostic tools, including invasive imaging procedures, have been advocated in infants and small children with UTIs but are not necessary in most cases. Effective antibiotic drugs are available, and prophylactic treatment has been questioned. Several guidelines on UTIs are available, but a simple one for general practitioners is needed.

Increasing interest surrounds the relation between Level of Personality Functioning (LPF), as defined by Criterion A of the Alternative Model for Personality Disorders, and the Hierarchical Taxonomy of Psychopathology (HiTOP) model. However, the integration of LPF within HiTOP remains unclear. Using bivariate correlation and linear regression analyses, this study assessed the associations between LPF and HiTOP spectra (externalizing antisocial, externalizing drug use, internalizing, antagonism, detachment, and psychoticism). A sample of 1,183 participants (46.2% female, M = 31.3 ± 14.8 years) from the Italian community completed various self-report measures to capture impairments in personality functioning, and several psychopathology symptoms. Bivariate correlations and regression analyses showed that the LPF facets were consistently associated with all HiTOP domains, even though the LPF measures used in this study appeared more reflective of internalizing symptoms than externalizing ones. The identity facet of LPF was uniquely associated with all outcome criteria, whereas no unique associations were evident for self-direction. Empathy facet had the highest association with antagonism while intimacy presented the highest relation with detachment. Overall, the evidence presented in this study partially supports the construct validity of Criterion A, highlighting its relevance across a wide range of psychopathological symptoms and its potential utility in clinical assessment beyond formal personality disorder diagnoses. Thus, this study may contribute to the understanding of LPF's role in the dimensional model of psychopathology and underscores the importance of considering personality functioning in the assessment and treatment of mental disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).age = 31.3 ± 14.8 years) from the Italian community completed various self-report measures to capture impairments in personality functioning, and several psychopathology symptoms. Bivariate correlations and regression analyses showed that the LPF facets were consistently associated with all HiTOP domains, even though the LPF measures used in this study appeared more reflective of internalizing symptoms than externalizing ones. The identity facet of LPF was uniquely associated with all outcome criteria, whereas no unique associations were evident for self-direction. Empathy facet had the highest association with antagonism while intimacy presented the highest relation with detachment. Overall, the evidence presented in this study partially supports the construct validity of Criterion A, highlighting its relevance across a wide range of psychopathological symptoms and its potential utility in clinical assessment beyond formal personality disorder diagnoses. Thus, this study may contribute to the understanding of LPF's role in the dimensional model of psychopathology and underscores the importance of considering personality functioning in the assessment and treatment of mental disorders. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Obstructive sleep apnoea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality and has a detrimental effect on vascular function, in particular on arterial stiffness and endothelial function. Continuous positive airway pressure (CPAP) is the gold-standard therapy for OSAS and its effects on arterial stiffness and endothelial function have been demonstrated in non-elderly patients., Objectives: The objective of this study was to evaluate the effect of one year of CPAP treatment on arterial stiffness, through assessment of carotid-femoral pulse wave velocity (cf-PWV), and on endothelial function, through the reactive hyperaemia index (RHi), in a real-life cohort of elderly patients with moderate-to-severe OSAS and several comorbidities., Methods: In this nonrandomised prospective study, we enrolled 469 consecutive elderly patients affected by moderate-to-severe OSAS distributed in two groups: CPAP-treated ( n = 225) and untreated patients ( n = 244)., Results: At one-year follow-up, in the treated group emerged an important improvement in poligraphics (AHI, ODI, TC90, mean SpO 2 %), laboratory (HOMA index, eGFR, hs-CRP) and vascular function parameters: cf-PWV. The stepwise multivariate linear regression demonstrated a significant correlation between the delta of the polygraph parameters and the delta of PWV and RHi., Conclusions: Our study confirmed the favourable effects of CPAP therapy in a cohort of elderly patients affected by OSAS and several comorbidities on sleep respiratory parameters and vascular function; early diagnosis and treatment with CPAP might be beneficial to delay or prevent the occurrence of cardiovascular events in these groups of patients.

Neuroactive steroids including allopregnanolone are implicated in the pathophysiology of peripartum depressive symptoms (PDS). We performed a systematic review searching PubMed/Embase/PsychInfo/Cinhail through 08/2023 (updated in 07/2024), and conducted a random-effects meta-analysis of studies comparing allopregnanolone blood concentrations in women with versus without PDS at various timepoints during the 2 nd and 3 rd trimester and the postpartum period, calculating standardized mean differences (SMDs) and 95% confidence intervals (CIs). Meta-regression and subgroup analyses included age, diagnoses of affective disorders before pregnancy, antidepressant treatment, analytical methods, and sample type. Study quality was assessed using the Newcastle-Ottawa-scale. The study protocol was registered on PROSPERO (registration number CRD42022354495). We retrieved 13 studies with 2509 women (n = 849 with PDS). Allopregnanolone concentrations did not differ between women with versus without PDS at any timepoint (p > 0.05). Allopregnanolone concentrations assessed during pregnancy did not differ for women with versus without PDS at postpartum follow-up (p > 0.05). Subgroup analyses indicated higher allopregnanolone concentrations in women with versus without PDS at gestational weeks 21-24 and 25-28 (SMD = 1.07, 95% CI = 0.04, 2.11 and SMD = 0.92, 95% CI = 0.26, 1.59 respectively). Moreover, we reported differences between studies using mass-spectrometry combined with chromatography versus immunoassays at gestational weeks 25-28 (p = 0.01) and plasma versus serum samples at gestational weeks 21-24 (p = 0.005). Study quality was rated as poor, good, and fair for two, one and ten studies respectively. PDS were not associated with differences for allopregnanolone concentrations. The use of heterogenous peripartum time points, study cohorts, depression symptom measures and analytical methods has hampered progress in elucidating neuroactive steroid signaling linked to PDS., (© 2024. The Author(s).)

We present a theoretical investigation on the esterification process for boron ester synthesis, considering boric acid and 2( R ),4( S )-pentanediol as model boron and diol derivatives, respectively. We report an unprecedented mechanistic pathway, able to rationalise, in contrast with the reported ones, the relatively low Gibbs energies of activation and the pH dependence experimentally observed in the formation of boron esters. We believe that these findings will improve the possibility to predict cross-link reaction rates of boron esters as a fundamental tool in the rational design of functional materials based on boron-oxygen linkages.

It is demonstrated that the eXtended Finite Element Method (XFEM) is of remarkable efficiency in simulating crack evolution by eliminating the need for remeshing and refinement. In this paper, it is shown how to enhance the solution efficiency through a comprehensive mathematical investigation of the solution process using XFEM. A typical example is presented to illustrate the disparities in nodal displacements along the two symmetric faces of the crack resulting from the approximation of XFEM. By analysing the structure and components of the global stiffness matrix, the underlying causes of these discrepancies are identified. Building upon these findings, two improvements of the solution are proposed to gain an acceptable accuracy in computing the nodal displacements. The first improvement consists of the subdivision of the enriched elements depending on the characteristic of the distribution of Gauss points. The second improvement is set by determining the optimal number of Gauss points in each sub-element near the crack tip. To calculate the stress intensity factor of the crack under surface pressure, such improvements are applied in conjunction with the interaction integral method, which significantly reduces computational time and eliminates the influence of surface tractions. The numerical solution is validated by comparing it with the analytical solution and the standard XFEM solution. The proposed improvements can enhance both the accuracy of the solution and the computational efficiency of XFEM., (© 2024. The Author(s).)

Systemic sclerosis is considered a rare autoimmune disease in which there are alterations of both the innate and adaptive immune response resulting in the production of autoantibodies. Abnormalities of the immune system compromise the normal function of blood vessels leading to a vasculopathy manifested by Raynaud's phenomenon, an early sign of systemic sclerosis. As a consequence of this reactive picture, the disease can evolve leading to tissue fibrosis. Several systemic sclerosis-specific autoantibodies are currently known and are associated with specific clinical manifestations and prognosis. Although the pathogenetic role of these autoantibodies is still unclear, their production by B cells and plasma cells suggests the importance of these cells in the development of systemic sclerosis. This review narratively examines B cell dysfunctions and their role in the pathogenesis of systemic sclerosis and discusses B cell-targeted therapies currently used or potentially useful for the management of end-organ complications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology.)

Modern healthcare is experiencing a significant transformation, utilizing technology to improve patient outcomes and make processes more efficient. Breast cancer, being the most commonly diagnosed cancer in women globally, requires innovative approaches for effective management. Digital Therapeutics (DTx) and Clinical Decision Support Systems (CDSSs) have emerged as pivotal technologies, offering personalized, patient-centered care and optimizing clinical decision-making. This review provides a comprehensive analysis of the applications, benefits, and challenges of these digital tools in breast cancer treatment. We examine DTx tools' ability to offer real-time symptom monitoring, treatment adherence, psychological support, and lifestyle modification guidance. Simultaneously, the role of CDSSs in providing personalized treatment recommendations, early detection, data analysis, and enhancing multidisciplinary collaborations is evaluated. The challenges of implementing these technologies, such as data privacy, interoperability, and accessibility are also discussed, along with potential solutions. By exploring the current research findings, the review underscores the significant impact of DTx and CDSSs on patient outcomes, treatment efficiency, and overall quality of life. This manuscript concludes with a forward-looking perspective, emphasizing the importance of collaborative efforts to overcome obstacles and unlock the full potential of digital innovations in breast cancer oncology. Our analysis suggests that adopting these digital tools can lead to more holistic, efficient, and patient-centric cancer care, marking a significant shift in the paradigm of breast cancer management., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: The evidence of the long-term advantages of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) for aortic stenosis (AS) remains scarce., Methods: Patients with EuroSCORE II < 4 % who underwent TAVR or SAVR for AS from the prospective observational OBSERVANT study were included in this analysis. Ten-year survival was the primary outcome of this analysis. Secondary outcome was repeat procedure on the aortic valve prosthesis., Results: Propensity score matching resulted in 355 matched pairs of patients who underwent TAVR or SAVR. The mean age of SAVR patients was 80.0 ± 5.1 years and that of TAVR patients 80.1 ± 6.4 years (p = 0.81) and the mean EuroSCORE II was 2.5 ± 0.8 % and 2.6 ± 0.8 % (p = 0.60), respectively. Thirty-day mortality was 2.8 % after SAVR and 2.5 % after TAVR (p = 0.82). At 10-year, survival was 37.0 % (95 %CI 32.2-42.5 %) after SAVR and 18.2 % (95 %CI 14.5-22.8 %) after TAVR (Log-rank test, p < 0.001; HR 1.70, 95 %CI 1.42-2.03). Difference in terms of survival between the propensity matched cohorts became significant 3 years after the procedures. Ten-year cumulative incidences of repeat aortic valve procedure were 2.6 % (95 %CI 1.4-5.0 %) after SAVR and 1.1 % (95 %CI 0.4-3.0 %) after TAVR (p = 0.153; SHR 0.43, 95 %CI 0.13-1.41)., Conclusions: The results of this prospective observational, non-randomized study showed that 10-year survival of low-risk patients who underwent TAVR with early generation prosthesis devices was lower than SAVR., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Metal-on-metal (MoM) large headed arthroplasties were suggested to decrease failure rates by means of reduced volumetric wear and enhanced implant stability. However, they caused high rates of revisions due to adverse reaction to metal debris, osteolysis, pseudotumor growth, and other issues. The study aims to present the long-term outcomes of MoM arthroplasties on a large cohort of patients, evaluating the impact of head sizes on survival rate. All data were retrieved from the regional joint register (Registro dell'Implantologia Protesica Ortopedica, RIPO, Italy). We include in the study all patient who underwent cementless MoM total hip arthroplasties (THAs) between 2000 and 2020, dividing them in two subgroups according to head size (<36 mm, ≥36 mm). Failures were recorded up to December 31, 2020. Patients lost to follow-up were excluded. A total of 3813 THAs met the inclusion/exclusion criteria. The average follow-up period is 12.4 years (0-21 years). 178/1625 (or 11.0%) small head MoM THAs and 265/2188 large head ones failed by the end of follow up. Large diameter heads reported lower survival rate (p-value < 0.001), with unexpected higher dislocation rate (1.0 vs. 0.4%). Moreover, large head size was found to increases the risk of metallosis (p-value < 0.0001). Gender, patient's age and the use of modular neck were not correlated with higher failure rates. MoM implants implants do not have the same reliability as other couplings, considering the significantly greater failure/complication rates. However, the knowledge of risks linked to head size is fundamental for establishing the right type of follow-up to the patient and recognize any complications early., Competing Interests: Declarations. Conflict of interest: The authors declare no conflict of interest., (© 2024. The Author(s).)