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Spectrochemical analysis of trace elements in complex matrices is crucial across various fields of science, industry, and technology. However, this analysis is often hindered by background interference and the challenge of detecting ultralow analyte concentrations. Surface Enhanced Infrared Absorption (SEIRA) spectroscopy is emerging as a viable technique to address these challenges as it can successfully reveal soluble and unmodified analytes in a label-free manner through their interactions with a bioreceptor following site-specific labeling with small infrared-active probes. In this study, we present and demonstrate an advanced method for mid-infrared spectroscopy utilizing a pixeled SEIRA substrate coupled with a peculiar infrared-active vibrational probe. We select a small azide moiety as the vibrational tag since its signature around 2100 cm -1 is in the cell- and protein-silent window and its small size preserves the structure and biological function of the protein it integrates into. As model bioreceptor, we utilize an antigen-binding fragment (Fab') derived from the therapeutic antibody trastuzumab, modified with azidoacetic acid, and its Her2 antigen as the soluble analyte. Employing mid-infrared SEIRA spectroscopy, we are able to monitor the immobilization of the azide-modified Fab', and demonstrate the detection of analyte quantities as low as 83 amol within an area of 100 μm 2 ., 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 Authors. Published by Elsevier B.V. All rights reserved.)

A rapid and non-invasive mass spectrometry-based electronic nose (MS-eNose) method, combined with chemometric analysis, was developed for the early detection of Aspergillus westerdijkiae on caciocavallo cheeses during ripening process. MS-eNose analyses were carried out on caciocavallo inoculated with ochratoxin A (OTA) non-producing species and artificially contaminated with A. westerdijkiae, an OTA producing species. Two classification models, i.e. PLS-DA and PC-LDA, were used to discriminate cheese samples in two classes, based on their contamination with toxigenic or non-toxigenic fungal species. Accuracy values were between 87 and 100 % and 86-100 %, in calibration and validation, respectively, with best results obtained at 15-ripening days with 98 % (PLS-DA) and 100 % (PC-LDA) of accuracy in validation. Moreover, eighteen potential volatile markers of the presence of A. westerdijkiae were identified by GC-MS analysis. Results show that MS-eNose represents a useful tool for a rapid screening in preventing A. westerdijkiae and related OTA contamination in caciocavallo cheese during ripening process., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with pericarditis may show elevation of C-reactive protein (CRP) and pericardial effusion at presentation. There are limited data on the prognostic implications of this inflammatory phenotype., Objectives: Aim of the present study is to evaluate the outcome of the inflammatory phenotype in a cohort of patients with acute pericarditis., Methods: Observational cohort study of consecutive adult patients with acute pericarditis in 4 referral centers for pericarditis (Athens, Milan, Turin, Udine)., Results: Our cohort included 918 patients with acute pericarditis (median age of 56, IQR 28 years, 55.6 % females). The etiology of pericarditis was respectively idiopathic in 82.1 %, post-cardiac injury syndrome in 9.3 %, and systemic inflammatory disease in 4.9 % of cases. CRP elevation was detected at presentation in 778 cases (84.7 %), an inflammatory phenotype (CRP elevation and pericardial effusion) was found in 557 patients (60.7 %). Baseline medical therapy included a NSAID in 74.9 %, colchicine 70.9 %, and corticosteroids 25.1 % of cases. After a mean follow-up of 22.5 months, patients with an inflammatory phenotype had a higher recurrence rate at 18 months (respectively 46.0 % vs. 31.0 %; p < 0.0001), and a shorter recurrence-free survival (Log-rank p = 0.0001). In multivariable analysis the inflammatory phenotype presentation was independently associated with an increased risk of recurrences (OR 2.005, 95 % CI 1.454 to 2.765; p < 0.0001)., Conclusions: The inflammatory phenotype of presentation of acute pericarditis is associated with an increased risk of recurrences, highlighting the importance of timely individualized therapy and close follow-up for these patients., Competing Interests: Declaration of competing interest None., (Copyright © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The impact of hormone replacement therapy (HRT) on the cardiovascular (CV) system in menopausal women has been the subject of significant debate for many years. After a phase marked by restrictive use following the outcomes of the first randomized trials in the 2000s, the last decade has witnessed a significant reassessment of the risks and benefits of therapy, especially CV risk. Thanks to new studies conducted in more selected populations and sub-analyses of earlier trials, there is now ample evidence regarding the high safety profile of HRT, and even protection on the CV system, for young women with a low CV risk profile in the early menopausal phase. This evidence has been incorporated into all national and international menopausal guidelines and, recently, also in a consensus document by the European Society of Cardiology. Therefore, the cardiologist assumes a central role in the risk assessment and treatment of modifiable CV risk factors during the menopausal transition, a critical period for women as it is associated with significant changes in the glycometabolic balance. This article summarises current knowledge on the subject and provides practical guidance for the cardiological management of such patients.

Heart failure (HF) is a clinical syndrome with high morbidity and mortality, characterized by periods of relative clinical stability and exacerbations of HF, known as worsening heart failure (WHF). WHF is currently defined as a deterioration of HF signs and symptoms, necessitating an intensification of medical therapy, often identified by an increase in diuretic therapy. Episodes of WHF, whether they result in patient hospitalization or outpatient management, suggest clinical progression of HF with significant worsening of the prognosis. Although the prognostic impact of WHF is well documented in the literature, its current definition has limitations, and its management remains suboptimal and non-standardized, particularly in outpatient settings. Additionally, early detection of WHF episodes, preventing possible patient hospitalization, is crucial for improving prognosis and is still underemphasized in major HF clinical trials. This review aims to report the prevalence of WHF and the limitations of its current definition, and to provide suggestions for the appropriate management of WHF episodes, with a special focus on early and outpatient recognition.

Objectives: To investigate whether 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([ 18 F]F-FDG PET/CT) metabolic parameters were associated with histology and to assess their prognostic role in patients with thymic lesions., Patients and Methods: In total, 116 patients (49/67 M/F; mean age 59.5 years) who underwent preoperative [ 18 F]F-FDG PET/CT and thymectomy from 2012 to 2022 were retrospectively analyzed. Associations between histology and metabolic parameters (maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), ratio between target lesion and liver SUVmax (rPET), quotient of SUVpeak in the tumor residual and SUVmean in a 20-cm 3 volume of interest (qPET), and tumor-to-mediastinum (T/M) were analyzed. Freedom from recurrence (FFR) was determined and compared using the Kaplan-Meier and the log-rank test. The median follow-up was 38 months (range 14-72 months)., Results: In total, 27 thymic hyperplasia, 41 low-risk thymomas (LRT) (types A, AB, and B1), and 48 high-risk thymomas (HRT) (B2, B3 thymoma, and carcinoma) were included. SUVmax, SUVmean, SUVpeak, rPET, qPET, and T/M were significantly higher in HRT than LRT and hyperplasia (p < 0.001). TLG and MTV were significantly higher in patients with LRT (p < 0.001). Only rPET, qPET, and T/M remained significantly higher in HRT than in LRT subgroups (p = 0.042, p = 0.049, and p = 0.028, respectively). SUVmax, SUVmean, and SUVpeak cutoffs of < 4.3, < 2.87, and 4.03, respectively, significantly distinguished patients with longer FFR (p = 0.009, p = 0.05, and p = 0.05)., Conclusions: Positron emission tomography (PET) metabolic parameters could help to differentiate thymic histotypes. Standardized uptake value (SUV)-based parameters appear promising to predict recurrent disease., Competing Interests: Declarations. Funding: Daniele Antonio Pizzuto has been awarded financial support by Fondazione Umberto Veronesi ETS as winner of the Post-Doctoral Fellowship 2023. The authors do not declare any other funds, grants, or other support during the preparation of this manuscript. Conflit of interest: All authors (DAP, AC, MC, MC, SA, AC, GC, MC, LR, GC, FL & PM) declare that they have no relevant financial or nonfinancial interests to disclose. Author contributions: All authors contributed to the study conceptualization. Methodology, investigation, project administration, data curation, resources, software, validation, and visualization were performed by Angelo Castello, Daniele Antonio Pizzuto, Massimo Castellani, Salvatore Annunziata, Annalisa Campanella, Giuseppe Calabrese, Margherita Cattaneo, Lorenzo Rosso, and Giacomo Cusumano. Formal analysis was performed by Angelo Castello. The original draft of the manuscript was written by Daniele Antonio Pizzuto, Angelo Castello, and Marco Chiappetta. The writing (review and editing) was performed by Filippo Lococo and Paolo Mendogni. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics approval: The study was approved by the local Ethics Committee and partner institutional review boards of the promoting institution (Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome. Study identification: 2021/3027). All patients were previously informed and signed their agreement before undergoing [18F]F-FDG PET/CT, in accordance with the Declaration of Helsinki. Consent (participation and publication): Not applicable. Data availability statement: All data generated or analyzed during this study are included in this published article. Code availability: Not applicable., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: The aim of this project is to assess interobserver agreement for programmed death-ligand 1 (PD-L1) scoring on of non-small cell lung cancer (NSCLC) on cytological specimens in a large-scale multicenter study, by exploiting the cell block-derived tissue microarray (cbTMA) approach., Methods: A total of 65 cell blocks (CB) diagnosed as NSCLC were retrospectively collected and selected for TMA preparation. Hematoxylin-eosin and PD-L1 stained slides were digitized and uploaded on a free web sharing platform. Participants were asked to provide PD-L1 assessment by using the clinically relevant cutoff of tumor proportion score (TPS) (<1%; 1%-49%; >50%). Interobserver agreement was calculated using Fleiss's κ., Results: Of 65 CBs, 11 were deemed not suitable; therefore, an overall number of 54 cores were used for the preparation of four TMAs. A total of 1674 evaluations were provided by 31 cytopathologists from 21 different institutions in nine countries. The statistical analysis showed a moderate overall agreement (κ = 0.49). The highest agreement was achieved in the TPS >50% category (κ = 0.57); moderate agreement was observed in TPS <1% category (κ = 0.51) and the lowest κ value was obtained for TPS 1%-49% category (k = 0.32)., Conclusions: The overall moderate agreement observed showed that there is still room for improvement in inter-pathologist agreement for PD-L1 evaluation on cytological samples, highlighting the need for standardization in sample preparation, focused training in PD-L1 evaluation on cytological material, and the integration of machine learning tools to improve interobserver consistency., (© 2025 The Author(s). Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Purpose: To investigate surgical and oncologic outcomes of secondary cytoreductive surgery for ovarian cancer recurrence, considering the exposure to previous first-line maintenance therapy., Methods: We retrospectively identified all women who underwent secondary cytoreductive surgery for ovarian cancer recurrence with cytoreductive intent at three Italian Gynecologic Oncology centers (1997-2022). Data on clinical, surgical, and pathological characteristics, neoadjuvant, adjuvant, and maintenance therapy, as well as follow-up information, were retrieved from prospectively collected databases and medical records., Results: We identified 189 patients. Maintenance therapy in the first-line setting was implemented in 108/189 (57 %) cases: bevacizumab in 77.7 % (84/108), PARP inhibitors (Olaparib, Niraparib, or Rucaparib) in 15.7 % (17/108), and bevacizumab + PARP-inhibitors in 4.6 % (5/108). Complete cytoreduction rate and perioperative complications in secondary surgery were not associated with previous maintenance therapy. Complete cytoreduction was achieved in 75 % (140/189) of patients, and any residual tumor was the strongest predictor of poor progression-free (Hazard ratio [HR] 3.91, 95 %CI 2.48-6.16) and cause-specific survival (HR 4.27, 95 %CI 2.36-7.70). First-line bevacizumab was independently associated with worse progression-free survival among patients with any residual tumor at secondary surgery. First-line PARP inhibitors were independently associated with worse progression-free and cause-specific survival regardless of complete cytoreduction. Second-line maintenance therapies were independently associated with better survival regardless of residual tumor after secondary surgery., Conclusion: Complete cytoreduction during secondary surgery for ovarian cancer recurrence is the strongest predictor of prognosis. First-line maintenance therapies do not appear to affect the safety and feasibility of secondary cytoreduction, although they may influence prognosis after secondary surgery., 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 © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Some studies about myocarditis and pericarditis following COVID-19 vaccination raised concerns worldwide. However, the heterogeneous diagnostic criteria for postvaccination inflammatory heart diseases may result in overestimating incidence rates. The aim of this multicentre Italian registry is to evaluate the impact of COVID-19 vaccines on the incidence of myocarditis and pericarditis in the Italian population., Methods: Consecutive patients admitted to Italian hospitals for endomyocardial and/or cardiac magnetic resonance proven acute myocarditis and/or pericarditis in the same period (1 June-31 October) of 2019 and 2021 were enrolled, irrespective of the potential association with the COVID-19 vaccines. Acute pericarditis and/or myocarditis were defined as 'vaccine-related' if clinical presentation occurred within 15 days after COVID-19 vaccination, independently of the dose., Results: There was a comparable incidence rate ratio (IRR) for inflammatory heart diseases in 2019 and 2021 (2019: IRR 0.67 versus 2021: IRR 0.74, P = 0.45). In particular, the IRR did not differ in myocardial involvement (2019: IRR 0.33 versus 2021: IRR 0.33, P = 1) and pericarditis (2019: IRR 0.37 versus 2021: IRR 0.49, P = 0.09) in both periods. Among 125 cases registered in 2021, 32 (25.6%) were 'vaccine-related'. Among those who experienced 'vaccine-related' myocarditis and/or pericarditis, men with age under 40 years were over-represented (53.12%, P = 0.021)., Conclusion: In a nationwide Italian survey comparing pandemic with prepandemic periods, the overall data do not indicate significant concerns about an increased incidence of pericarditis and myocarditis, suggesting that the vaccine is generally well tolerated for these specific conditions., (Copyright © 2025 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Last year, the European Society of Cardiology (ESC) published the first guidelines to comprehensively address the management of cardiomyopathies. This document by the Working Group on Myocardial and Pericardial Diseases of the Italian Society of Cardiology aims at highlighting the most relevant messages and novelties introduced by these guidelines for the management of patients affected by cardiomyopathies. Five main messages are summarized: the key role of the phenotype, the new classification of cardiomyopathies provided in the ESC guidelines, the importance given to new techniques such as cardiac magnetic resonance (CMR) and genetic testing, the newly provided recommendations given on sport activities and finally how the importance of follow-up evaluations is highlighted. These five main messages are then further analyzed more in depth so as to inform the reader on all the main novelties of the guidelines and to provide a critical approach to this important document., (Copyright © 2025 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: The surgical pathway represents a fundamental process in hospital productivity, and its digitalization is a major focus for hospital management. ASL Roma 1 health authority has taken up this digitalization challenge by introducing an Operation Room Management (ORM) system within the operating block of one of its hospital facilities in 2022., Study Design: Interrupted Time Series analysis., Methods: To evaluate the impact of Operation Room Management system adoption, data on surgery were collected from all inter-ventions performed during two periods: January-June 2019 and January-June 2023. Analysis of the Operation Room Management system utilization rate since its introduction was performed, to estimate staff adaptation to the new software., Results: As of June 2023, paper-registered interventions were 9%, nearing 100% for elective procedures only. The difference between the average intervention times was significantly in favor of the Operation Room Management cohort when restricting the analysis to Orthopedics (-9.02 minutes, p=0.006) and Surgery (8.47 min, p = 0.03). There was a modest but significant impact of Operation Room Management on the 'entering Operation Room to Incision' time (5 min, p < 0.01)., Conclusion: Overall, the adoption of the Operation Room Management did not worsen process outcomes. Operation Room Mana-gement offers advantages in real-time data quality, integrated with territorial and hospital platforms, contributing to a favorable cost-benefit assessment of digitalization.

Background: The histological assessment of colorectal precancer and cancer lesions is challenging and primarily impacts the clinical strategies of secondary colon cancer prevention. Artificial intelligence (AI) models may potentially assist in the histological diagnosis of this spectrum of phenotypical changes., Objectives: To provide a current overview of the evidence on AI-based methods for histologically assessing colonic precancer and cancer lesions., Methods: Based on the available studies, this review focuses on the reliability of AI-driven models in ranking the histological phenotypes included in colonic oncogenesis., Results: This review acknowledges the efforts to shift from subjective pathologists-based to more objective AI-based histological phenotyping. However, it also points out significant limitations and areas that require improvement., Conclusions: Current AI-driven methods have not yet achieved the expected level of clinical effectiveness, and there are still significant ethical concerns that need careful consideration. The integration of "artificial histology" into diagnostic practice requires further efforts to combine advancements in engineering techniques with the expertise of pathologists., Competing Interests: Conflict of interest none of the authors have competing interests to declare, (Copyright © 2024. Published by Elsevier Ltd.)

Managing acute myeloid leukemia (AML) and its critical complications requires understanding the complex interplay between disease biology, treatment strategies, and patient characteristics. Complications like sepsis, acute respiratory failure (ARF), hyperleukocytosis, coagulopathy, tumor lysis syndrome (TLS) and central nervous system (CNS) involvement present unique challenges needing precise evaluation and tailored interventions. Venetoclax-induced TLS and differentiation syndrome (DS) from IDH1/IDH2 or menin inhibitors highlight the need for ongoing research and innovative approaches. As the microbiological landscape evolves and new therapeutic agents emerge, adapting strategies to mitigate harmful pharmacological interactions is crucial. Advances in understanding the genetic profiles of patients with hyperleukocytosis contribute to better-targeted therapeutic strategies. Effective AML management relies on collaborative efforts from hematologists, specialized services, and intensive care units (ICUs). This review analyzes recent data on critical AML complications, identifies areas for further investigation, and proposes ways to advance clinical research and enhance patient care strategies.

Background: Positron Emission Tomography-Computed Tomography using Prostate-Specific Membrane Antigen (PSMA PET/CT) is notable for its superior sensitivity and specificity in detecting recurrent PCa and is under investigation for its potential in pre-treatment staging. Despite its established efficacy in nodal and metastasis staging in trial setting, its role in primary staging awaits fuller validation due to limited evidence on oncologic outcomes. This systematic review and meta-analysis aims to appraise the diagnostic accuracy of PSMA PET/CT compared to CI for comprehensive PCa staging., Methods: Medline, Scopus and Web of science databases were searched till March 2023. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed to identify eligible studies. Primary outcomes were specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of PSMA PET/CT for local, nodal and metastatic staging in PCa patients. Due to the unavailability of data, a meta-analysis was feasible only for detection of seminal vesicles invasion (SVI) and LNI., Results: A total of 49 studies, comprising 3876 patients, were included. Of these, 6 investigated accuracy of PSMA PET/CT in detection of SVI. Pooled sensitivity, specificity, PPV and NPV were 42.29% (95%CI: 29.85-55.78%), 87.59% (95%CI: 77.10%-93.67%), 93.39% (95%CI: 74.95%-98.52%) and 86.60% (95%CI: 58.83%-96.69%), respectively. Heterogeneity analysis revealed significant variability for PPV and NPV. 18 studies investigated PSMA PET/CT accuracy in detection of LNI. Aggregate sensitivity, specificity, PPV and NPV were 43.63% (95%CI: 34.19-53.56%), 85.55% (95%CI: 75.95%-91.74%), 67.47% (95%CI: 52.42%-79.6%) and 83.61% (95%CI: 79.19%-87.24%). No significant heterogeneity was found between studies., Conclusions: The present systematic review and meta-analysis highlights PSMA PET-CT effectiveness in detecting SVI and its good accuracy in LNI compared to CI. Nonetheless, it also reveals a lack of high-quality research on its performance in clinical T staging, extraprostatic extension and distant metastasis evaluation, emphasizing the need for further rigorous studies., Competing Interests: Competing interests: Cosimo De Nunzio, Editor in Chief of prostate Cancer and Prostatic Disease., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Daridorexant is a dual orexin receptor antagonist approved for the treatment of chronic insomnia disorder., Aims: Investigate the auditory awakening threshold (AAT), postural stability, and cognitive function during the night following evening administration of daridorexant 25 and 50 mg., Methods: Double-blind, placebo-controlled, randomized, 3-way (placebo, 25, 50 mg) crossover study in 36 healthy male and female nonelderly adult and elderly subjects (1:1 sex/age ratio). Four hours after bedtime administration, the AAT was determined, followed by investigation of the main pharmacodynamic endpoint nocturnal postural stability (body sway) as well as functional mobility using the Timed Up and Go (TUG) test, and cognitive function/memory using the Visual Verbal Learning Test (VVLT)., Results: All 36 subjects completed the study. The average AAT was approximately 60 dB across treatments, i.e., there were no differences between daridorexant and placebo. Daridorexant marginally increased body sway by approximately 22%, while it had no clinically meaningful effect on the time to complete the TUG test (⩽1 s increase), and the VVLT (immediate and delayed number of correctly recalled words) showed minimal and clinically not meaningful differences of up to one word, all compared to placebo. Delayed word recognition was not different from placebo. The increase in body sway in the overall population was driven by nonelderly adults, as effects in elderly subjects were similar to placebo., Conclusions: Following bedtime administration, daridorexant maintained the ability to awaken to an external noise stimulus in the middle of the night, allowing subjects to function safely., Clinicaltrials.gov Identifier: NCT05702177., 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: At the time of study set-up and study conduct, M. Magliocca was employed by the Department of Clinical Pharmacology at Idorsia Pharmaceuticals Ltd, the study sponsor, and, when writing this article, employed by CHDR, the clinical research organization that conducted the study and received financial remuneration. I. Koopmans served as the project manager at the CHDR. R. Zuiker was the principal investigator at the CHDR. C. Vaillant, V. Lemoine, J. Dingemanse, and C. Muehlan were employees of Idorsia Pharmaceuticals Ltd. The authors assert no other pertinent affiliations or financial engagements with any organisations or entity regarding the research, authorship, and/or publication of this article.

Although Cannabis sativa L. is well known for being prolific in phytocannabinoids, their biosynthetic modular mechanism is ruled by a main enzyme: the geranyltransferase able to pursue the C-isoprenylation of olivetolic acid with the geranyldiphosphate. However, the existence of more than 160 meroterpenoids can be partially explained by a side degree of promiscuity of the geranyltransferase itself, able to recognise different substrate than the ordinary ones. This biological process led to the identification of several unconventional phytocannabinoids with a limited distribution in the plant both for occurrence and concentration. Taking advance of the existing synthetic protocols and using as example the enzymatic promiscuity, we propose a bio-inspired synthesis of naturally occurring minor cannabinoids related to the cannabigerol-type and their preliminary biological inspection in U87, U251 and T98 human glioblastoma cell lines to investigate their potential contribute as supplement in anticancer therapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Federica Pollastro reports financial support was provided by University of Eastern Piedmont Amedeo Avogadro Department of Pharmaceutical Sciences. Prof. Orazio Taglialatela-Scafati, the editor on chief, is listed between the authors If there are other authors, they 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 © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Predicting response to targeted cancer therapies increasingly relies on both simple and complex genetic biomarkers. Comprehensive genomic profiling using high-throughput assays must be evaluated for reproducibility and accuracy compared with existing methods., Methods: This study is a multicenter evaluation of the Oncomine™ Comprehensive Assay Plus (OCA Plus) Pan-Cancer Research Panel for comprehensive genomic profiling of solid tumors. A series of 193 research samples (125 DNA and 68 RNA samples) was analyzed to evaluate the correlation and concordance of the OCA Plus panel with orthogonal methods, as well as its reproducibility (n = 5 DNA samples) across laboratories., Results: The success rate for DNA and RNA sequencing was 96.6% and 89.7%, respectively. In a single workflow, the OCA Plus panel provided a detailed genomic profile with a high success rate for all biomarkers tested: single nucleotide variants/indels, copy number variants, and fusions, as well as complex biomarkers such as microsatellite instability, tumor mutational burden, and homologous recombination deficiency. The concordance for single nucleotide variants/indels was 94.8%, for copy number variants 96.5%, for fusions 94.2%, for microsatellite instability 80.8%, for tumor mutational burden 81.3%, and for homologous recombination deficiency 100%. The results showed high reproducibility across the five European research centers, each analyzing shared pre-characterized tissue biopsies (average of 1890 single nucleotide variants/indels per sample)., Conclusions: This multicenter evaluation of the OCA Plus panel confirms the results of previous single-center studies and demonstrates the high reproducibility and accuracy of this assay., Competing Interests: Declarations. Funding: This study was supported in part by Thermo Fisher Scientific in the form of reagents. The content is solely the responsibility of the authors. Conflict of interest: Dilce Gozuyasli, Cecília Durães, and José Luis Costa are employees of Thermo Fisher Scientific. Eloisa Jantus-Lewintre, Alessandra Rappa, Dina Ruano, Demi van Egmond, Sandra Gallach, Carlos Camps, Ludovic Lacroix, Karl Kashofer, Tom van Wezel, and Massimo Barberis have no conflicts of interest that are directly relevant to the content of this article. Ethics approval: This retrospective study was based on pre-existing biological materials and data, which were reanalyzed using a new method. All procedures were conducted in accordance with the ethical standards outlined by the relevant institutional and/or national research committees and adhered to the principles of the Helsinki Declaration (revised in 2013). The study received approval from the following ethics committees: Medical University of Graz (33-112 ex 20/21), Istituto Europeo di Oncologia (IEO DSC.MO.7720), Leiden University Medical Center (following the Code Proper Secondary Use of Human Tissue established by the Dutch Federation of Medical Sciences, https://www.federa.org/ ), Institut Gustave Roussy (s/n), Fundación Investigación Hospital General Universitario (s/n). Consent to participate: Written informed consent was obtained from all patients to use their biological samples for research purposes. Consent for publication: Not applicable. Availability of data and material: The datasets generated and/or analyzed during this study are available from the corresponding author upon reasonable request. Code availability: Not applicable. Author contributions: MB and JLC designed the study; EJ-L, CC, LL, KK, and TvW performed the data interpretation; AR, DR, DvE, and SG performed the experiments and data analysis; DG and CD performed the data analysis and visualization; EJL, CC, LL, KK, TvW, MB, DR, and DG revised the manuscript; CD and JLC reviewed and edited the manuscript. All authors have read and agreed to the final version of the manuscript., (© 2025. The Author(s).)

Introduction: White matter (WM) tract degeneration is a characteristic feature of progressive supranuclear palsy (PSP), with longitudinal changes observed in PSP-Richardson's syndrome (PSP-RS). Little, however, is known about the other PSP variants. We assessed cross-sectional and longitudinal WM degeneration across PSP variants using diffusion tractography., Methods: Forty-eight PSP patients were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent two diffusion MRI, 1-year apart. We measured fractional anisotropy and mean diffusivity from eight WM tracts reconstructed using deterministic tractography. Baseline and rates of change were compared across PSP variants grouped into PSP-RS, PSP-cortical, and PSP-subcortical, and correlated with clinical disease severity., Results: PSP-RS, PSP-cortical and PSP-subcortical showed overlapping but distinct baseline patterns of WM alterations. Longitudinally, faster rates of degeneration were observed in the superior cerebellar peduncle (SCP) and dentatorubrothalamic tract (DRTT) in all groups compared to controls. In PSP-RS, the anterior thalamic radiation also showed faster rates of degeneration compared to controls. PSP-cortical had faster rates of degeneration in many WM tracts compared to controls and other PSP groups, including body of corpus callosum, superior thalamic radiation, superior corticostriatal tract, superior longitudinal fasciculus, and frontal aslant tract. Progression in the PSP-subcortical group was limited to SCP and DRTT. Greater rates of degeneration in the corpus callosum and SCP correlated with worsening disease severity., Conclusions: Different progression patterns of WM degeneration characterize the PSP variants, although degeneration of the SCP is a common feature and could be a useful potential biomarker for clinical treatment trials in PSP., Competing Interests: Declaration of competing interest As the corresponding author I confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. We have no declaration of competing interest pertinent to this study. I confirm that I take full responsibility for the data, the analyses and interpretation, and the conduct of the research., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Objectives: The environmental footprint of iodinated contrast agents (ICAs) and gadolinium-based contrast agents (GBCAs) is noteworthy. This study assesses: (1) patients' "green sensitivity" as measured by their acceptance in a sustainability study and (2) the resulting potential reduction of contrast residuals in wastewater., Materials and Methods: After ethical approval, participants scheduled for administration of ICAs or GBCAs for diagnostic purposes were enrolled in this prospective observational study from July 2022 to October 2023. They were asked to prolong their hospital stay by up to 60 min to collect their first urine in dedicated canisters, thereby measuring the recovery rates of ICAs and GBCAs as found/theoretical ratio of concentrations. Mann-Whitney U, χ 2 tests, and multivariable regression analysis were used., Results: Patients scheduled for contrast-enhanced CT or MRI (n = 455) were screened; 422 (92.7%) accepted to participate. We enrolled 212 patients administered with ICAs and 210 administered with GBCAs. The median recovery rate was 51.2% (interquartile range 29.2-77.9%) for ICAs and 12.9% (9.0-19.3%) for GBCAs. At multivariable analysis, a significant effect of patient age (ICAs, p = 0.001; GBCAs, p = 0.014), urine volume (p < 0.001 for both), and time interval from contrast administration to urine collection (p < 0.001 for both) on recovery rates was found for both contrast agents; injected contrast volume (p = 0.046) and saline flushing usage (p = 0.008) showed a significant effect only for ICAs., Conclusion: The high patient enrollment compliance (93%) and potential recovery rates of 51% (ICAs) and 13% (GBCAs) play in favor of sustainable practices in reducing the environmental footprint of contrast agents., Key Points: Question How many patients are willing to extend their stay in radiology by up to 60 min to help reduce the environmental impact of contrast agents? Findings Over 90% of screened patients agreed to extend their stay by up to 60 min and collect their urine in dedicated containers. Clinical relevance Patients demonstrated a high willingness to cooperate in reducing the environmental impact of contrast agents, allowing for a potential recovery of approximately 51% for iodinated and 13% for gadolinium-based contrast agents., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is F.S. Conflict of interest: The authors of this manuscript declare relationships with the following companies: F.S. has received research grants from Bracco, Bayer, GE. F.P. is an employee of ArsChemica S.R.L. The other authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article. Statistics and biometry: Professor Federico Ambrogi, Full Professor of Medical Statistcs at the University of Milan, kindly provided statistical advice for this manuscript. Informed consent: Written informed consent was obtained from all subjects enrolled in this study. Ethical approval: The GREENWATER study has been approved by the local Ethics committee (Comitato Etico Ospedale San Raffaele, then Comitato Etico Territoriale Lombardia 1, Milan, Italy; protocol number 53/INT/2022) on May 11, 2022, and emended on September 26, 2023. Study subjects or cohorts overlap: None. Methodology: Prospective Cross-sectional study/observational Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background and Aims: The aim of the present study was to assess prevalence and disease outcomes of arthritis in a nationwide cohort of pediatric patients with inflammatory bowel disease (IBD)., Methods: We collected data of pediatric IBD patients experiencing arthritis from the Italian Society of Pediatric Gastroenterology, Hepatology and Nutrition IBD registry. We gathered baseline and one-year follow-up data on concomitant IBD and arthritis diagnosis., Results: 150 patients [(99 Crohn's Disease (CD), 51 Ulcerative Colitis (UC) and Unclassified IBD (IBDU)] with arthritis out of 3061 (1301 CD and 1760 UC) patients were identified, with an overall prevalence of 4.9 %. Arthritis was more frequent in CD than in UC (7.6 % vs 2.9 %, p < 0.01). Peripheral arthritis was more frequently diagnosed in patients with active IBD than in those with quiescent disease (94.6 % vs 67.3 %, p < 0.01). At one-year follow-up, clinically active IBD was independently associated with lower peripheral arthritis remission rates, whereas it did not impact axial arthritis remission. The presence of additional EIMs was associated with lower IBD clinical remission rates., Discussion: Clinically active IBD impacts peripheral arthritis but not axial one, whose activity appeared to be independent by intestinal disease. The presence of additional EIMs has a negative prognostic impact on IBD course., Competing Interests: Conflict of interest The authors have no conflict of interest to declare., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

De novo onset of Graves' disease (GD) after controlled ovarian stimulation (OS) is exceptional. Only one case of progression to GD after OS in a patient with pre-existing subclinical hyperthyroidism has been reported. We describe the case of a patient with neither previous thyroid disorders nor autoimmunity who developed GD after OS for primary infertility. A 40-year-old woman with primary infertility underwent four cycles of OS. Her thyroid function performed before the last cycle was unremarkable (thyroid stimulating hormone [TSH] 1.9 mU/L, fT4 1.3 ng/dL, fT3 2.4 pg/mL), and thyroid autoimmunity was negative (anti-thyroperoxidase antibodies and anti-thyroglobuline antibodies). Six weeks after the last cycle she developed overt thyrotoxicosis (TSH < 0.005 mU/L, fT4 4.79 ng/dL, fT3 15.6 pg/mL) with anti-thyrotropin receptor antibodies (TRAb) positivity (9.2 IU/L). She was diagnosed with GD and anti-thyroid therapy was instituted. After 1 year of treatment, thyroid function was still suboptimal (TSH 0.2 mU/L, fT4 1.04 ng/dL, fT3 2.2 pg/mL), and TRAb titer still elevated (8.75 IU/L). Despite her desire to achieve pregnancy, a further cycle of OS was postponed until complete remission of thyroid dysfunction and withdrawal of anti-thyroid therapy. Although TSH assay after OS is not recommended in euthyroid women without autoimmunity, in the presence of hyperthyroid symptoms throughout OS it is advisable to evaluate thyroid function and TRAb. It is advisable to carefully evaluate the course of GD before proceeding with further courses of OS that could lead to its exacerbation or recurrence. In cases where a strong desire for pregnancy persists, thyroidectomy may be proposed., (© 2024 International Federation of Gynecology and Obstetrics.)

Liver transplantation (LT) is a curative strategy for hepatocellular carcinoma (HCC), but the risk of HCC recurrence remains a challenging problem. In patients with HCC recurrence after LT (HCC-R&#95;LT), the locoregional and surgical approaches are complex, and the guidelines do not report evidence-based strategies for the management of immunosuppression. In recent years, immunotherapy has become an effective option for patients with advanced HCC in pre-transplant settings. However, due to the risk of potentially fatal allograft rejection, the use of immunotherapy is avoided in post-transplant settings. Combining immunosuppressants with immunotherapy in transplant patients is also challenging due to the complex tumor microenvironment and immunoreactivity. The fear of acute liver rejection and the lack of predictive factors hinder the successful clinical application of immunotherapy for post-liver transplantation HCC recurrence. This review aims to comprehensively summarize the risk of HCC-R&#95;LT, the available evidence for the efficacy of immunotherapy in patients with HCC-R&#95;LT, and the clinical issues regarding the innovative management of this patient population., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To develop a universally accepted complexity and experience grading system to guide the safe implementation of robotic and laparoscopic minimally invasive pancreatoduodenectomy (MIPD)., Background: Despite the perceived advantages of MIPD, its global adoption has been slow due to the inherent complexity of the procedure and challenges to acquiring surgical experience. Its wider adoption must be undertaken with an emphasis on appropriate patient selection according to adequate surgeon and center experience., Methods: The International Study Group for Pancreatic Surgery (ISGPS) developed a complexity and experience grading system to guide patient selection for MIPD based on an evidence-based review and a series of discussions., Results: The ISGPS complexity and experience grading system for MIPD is subclassified into patient-related risk factors and provider experience-related variables. The patient-related risk factors include anatomic (main pancreatic and common bile duct diameters), tumor-specific (vascular contact), and conditional (obesity and previous complicated upper abdominal surgery/disease) factors, all incorporated in an A-B-C classification, graded as no, a single, and multiple risk factors. The surgeon and center experience-related variables include surgeon total MIPD experience (cutoffs 40 and 80) and center annual MIPD volume (cutoffs 10 and 30), all also incorporated in an A-B-C classification., Conclusions: This ISGPS complexity and experience grading system for robotic and laparoscopic MIPD may enable surgeons to optimally select patients after duly considering specific risk factors known to influence the complexity of the procedure. This grading system will likely allow for a thoughtful and stepwise implementation of MIPD and facilitate a fair comparison of outcomes between centers and countries., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Dual-energy computed tomography (DECT) could combine the high-resolution bone window images made available by multi-detector CT technology with its capability to identify bone marrow edema (BME) in the spine, for diagnosing spondylodiscitis. Our objective was to compare the diagnostic performance of contrast-enhanced MRI and non-contrast DECT to identify spondylodiscitis of the thoraco-lumbar spine., Materials and Methods: This prospective study included 77 consecutive participants (39 males; mean age of 61) who underwent DECT and MRI (within 7 days) between January 2020 and October 2023. DECT data were post-processed on a dedicated offline workstation (SyngoVia® VB20) by using a three-material decomposition algorithm. Four radiologists, blinded to clinical data, evaluated non-contrast DECT and contrast-enhanced MRI images. The diagnosis of spondylodiscitis was based on vertebral edema, disc edema, endplate erosions, and paraspinal involvement. Diagnostic accuracy values were calculated by using biopsy as a standard of reference. A multi-reader multi-case analysis was performed., Results: Biopsy revealed a diagnosis of spondylodiscitis in 46 patients (60%). Thoracic and lumbar spondylodiscitis were diagnosed in 37/46 (80%) and 9/46 (20%) patients, respectively. DECT and MRI overall sensitivity, specificity, and AUC were 0.91, 0.89, and 0.90, and 0.94, 0.93, and 0.93, respectively. At lumbar and thoracic levels, the difference between AUC values between DECT and MRI was not significant (p = 0.15). For DECT and MRI, a very good inter-reader agreement was achieved (k = 0.90 and k = 0.97, respectively)., Conclusions: Contrast-enhanced MRI represents the most accurate imaging tool for the diagnosis of spondylodiscitis. However, only a non-significant drop in diagnostic performance was achieved by evaluating non-contrast DECT images., Key Points: Question To compare the diagnostic performance of contrast-enhanced MRI and non-contrast DECT for identifying spondylodiscitis of the thoraco-lumbar spine. Findings MRI was not significantly superior compared to DECT in diagnosing spondylodiscitis, whereas the inter-reader agreement was near perfect for both MRI and DECT. Clinical relevance DECT represents a fast and accurate imaging tool for the demonstration of BME, erosions, and peri-vertebral inflammation in thoraco-lumbar spondylodiscitis., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Giovanni Foti. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: Massimo Guerriero, PhD, provided statistical advice for this manuscript. He was one of the authors and has significant statistical expertise. Informed consent: Written informed consent was obtained from all subjects (patients) in this study. Ethical approval: Institutional Review Board approval was obtained. Clinical trials registration number (Prot n. 26670; Prog. 3762CESC). Study subjects or cohorts overlap: No subjects or cohorts have been previously reported. Methodology: Prospective Diagnostic study Performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Bile Acid Diarrhea (BAD) is a common cause of chronic diarrhea, often accompanied by urgency, occasional fecal incontinence, abdominal pain, and fatigue. A nationwide survey has shown limited awareness of BAD within the Italian medical community, prompting a panel of experts to develop a Position Paper that outlines the most practical and cost-saving diagnostic investigations and treatments for this frequently overlooked condition. The document provides an overview of the epidemiology, pathophysiology, clinical manifestations, and classification of the different types of Bile Acid Diarrhea (BAD). A key focus is the diagnostic approach to identifying and managing the many undiagnosed BAD patients in both primary care and specialized medical settings. Finally, the paper addresses the optimal therapeutic strategies for BAD, including traditional bile acid sequestrants and newer, promising treatments., Competing Interests: Conflict of interest Annibale B.: Alfasigma, Aboca Barbara G.: Aboca, Ab Biotics, Agave, Alfasigma, Ag Pharma, Bayer, Biocodex, Boheringer, Bromatec, Cadigroup, Danone, Diadema, Falk Pharma, Ge Healthcare, Giuliani, Mayoly, Malesci, Monteresearch, Sanofi, Sofar, Yakult Bellini M.: Alfasigma, Diadema, Agave, Ferring, Ag Pharma, Bromatec, Sila, Depofarma Cammarota G.: Aurora Biopharma, Delta Pharma Corazziari E.S.: Aboca spa; Alfa Sigma spa; GE Healthcare; Sofar spa Fries W.: Abbvie, Pfizer, Janssen, Galapagos Portincasa P.: Aboca, Allergosan, Omega Pharma Stanghellini V.: Alfasigma, Bayer, Bromatec, Ge Healthcare Usai Satta P.: Alfasigma Benedetti A declares non-conflict of interest, (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Ischaemic heart disease (IHD) remains a major cause of death and morbidity. Klotho is a well-known anti-ageing factor with relevant cardioprotective actions, at least when renal dysfunction is present, but its actions are much less known when renal function is preserved. This study investigated Klotho as a biomarker and potential novel treatment of IHD-associated complications after myocardial infarction (MI) under preserved renal function. Association between circulating Klotho levels and cardiac injury was investigated in patients after ST-elevation MI (STEMI). Biochemical, in vivo and in vitro cardiac function and histological and molecular studies were performed to determine the effect of recombinant Klotho in the failing hearts of mice after MI. We demonstrated that STEMI patients showed lower systemic Klotho levels, with the lowest Klotho tertile in those patients with higher N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Mice also showed a decrease in systemic Klotho levels after MI induction. Furthermore, recombinant Klotho administration in mice reduced infarct area and attenuated cardiac hypertrophy and fibrosis. We also demonstrated that Klotho treatment prevented reduction in ejection fraction and MI-related ECG changes, including prolonged QRS, JT, QTc, and T peak T end intervals and premature ventricular contractions. In adult mouse cardiomyocytes, Klotho treatment restricted systolic calcium (Ca 2+ ) release and cell shortening disturbances after MI. Klotho prevented increased diastolic Ca 2+ leak and pro-arrhythmogenic events in PMI mice by blocking activation of the Ca 2+ /calmodulin-dependent kinase type II (CaMKII) pathway, preventing ryanodine receptor type 2 (RyR 2 ) hyperphosphorylation. In conclusion, Klotho supplementation protected against functional and structural cardiac remodelling and ameliorated ventricular arrhythmic events by preventing intracardiomyocyte Ca 2+ mishandling in mice following MI. These data uncover a new cardioprotective role of Klotho, emerging as a biomarker of ventricular injury and potential treatment for patients after MI. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Purpose: This study aims to investigate and compare High Dose Rate Brachytherapy (HDR-BT) with Helical Tomotherapy (HT) treatment plans. The focus is on small target volumes near radiation-sensitive organs in the ocular region, to evaluate the advantages of these techniques in treating skin cancer., Methods: This retrospective observational analysis included patients who underwent skin cancer HDR-BT Freiburg flap treatment between 2019 and 2023. An expert radiation oncologist contoured the planning target volumes (PTVs) and marked their visible extension with a radio-opaque tin wire. Each patient had two treatment plans: an individually shaped HDR-BT surface mold and an HT calculation used specifically for this study. Quality assurance of treatment plan was performed in both HDR-BT and HT. The plans were then compared using organ at risk (OAR) maximum doses and the conformity index CI. Radiation oncologists assessed their quality using their routine workflow evaluation plan., Results: Twelve patients were selected for the inclusion in this study. HT provided more consistent target coverage than HDR-BT, with a statistically significant difference (p < 0.05) at t-test. HT showed higher CIs and maximum dose for the optic nerve, optic chiasm, and lens in the homolateral part. Radiation oncologists preferred the overall quality of HT treatment due to its superior PTV coverage, especially for convex surfaces, while maintaining effective OAR sparing. HDR-BT is preferred when concave surfaces are present., Conclusion: HT offers more conformal treatment, although some OAR parameters are statistically significantly better with HDR-BT, which may also be superior for complex geometries., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Background: Geographic origin may represent a variable capable of influencing health status. This study aims to investigate the presence of differences of disease severity in Italian patients with fibromyalgia from different macro-regions., Methods: This retrospective, cross-sectional study involved patients included in the Italian Fibromyalgia Registry. Three geographical macro-regions were identified, comprising patients from Northern Italy, Central Italy and Southern Italy. Clinical differences (evaluated through PolySymptomatic Distress Scale [PSD], revised Fibromyalgia Impact Questionnaire [FIQR] and modified Fibromyalgia Assessment Status [FASmod]) among the geographical macro-regions were studied using one-way analysis of variance (ANOVA) and the Scheffé's test., Results: A total of 6095 patients (5719 females and 376 males) were included, with 1957 from Northern Italy, 2979 from Central Italy and 1159 from Southern Italy. All studied clinical indices showed a trend indicative of greater disease severity in Southern Italy, followed by Northern Italy and then Central Italy (mean values for PSD: 19.97 ± 6.20 in Northern Italy, 18.61 ± 7.12 in Central Italy, 23.01 ± 5.66 in Souther Italy). These differences were statistically significant for the overall scores of all studied indices, evaluated with ANOVA (all p < 0.001) and in the head to head comparisons, evaluted with Scheffé's test., Conclusions: Geographic background is significantly associated with variations in the severity of fibromyalgia in Italian patients., Significance Statement: This is the first study to demonstrate geographical origin-dependent intra-national differences in the severity of fibromyalgia. The results confirm the necessity of considering fibromyalgia within the context of the biopsychosocial model and of implementing healthcare policies targeted towards the most underserved regions., (© 2024 The Author(s). European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation ‐ EFIC ®.)

This study aims to test the efficiency of biochar-based substrates in removing chemical and bacteriological pollutants from wastewater and to determine the optimal percentage of biochar (BC) to implement for large-scale filters (e.g., constructed wetlands). So, a preliminary test was conducted on a lab column scale for wastewater treatment of decanted wastewater using column filtration systems (CFS) integrated with BC (BC-based CFSs) at different concentrations (0%, 10%, 25%, and 50%). The BC used here was produced from exhausted olive pomace (pyrolised at T 590 °C, residence time of 2 h and a heating rate of 10 °C min -1 ). The results revealed that the BC incorporated into the CFS improved the efficiency of nitrogen species removal (total nitrogen (TN) 64-65%, total kjeldahl nitrogen (TKN) 75%-77%, organic nitrogen (ON) 78%-87%, and NH 4 + -N 57%-69%); phosphorus species (total phosphorus (TP) 39%-44%, PO 4 3- 38%-42%); total and soluble chemical oxygen demand (TCOD (44%-56%), and SCOD (33%-51%) respectively); and total suspended solids (TSS) 87%-92%, compared to the control filter (CFS0). Bacteriological analysis focused on faecal bacteria indicators, including total coliforms (TC), faecal coliforms (FC), faecal streptococci (FS), as well as the pathogen Staphylococcus (SP) and total aerobic mesophilic flora (TAMF). The highest removal efficiencies were observed for CFS10. Based on this preliminary study, the efficiency of CFS in removing pollutants from wastewater is optimal with a small amount of BC (10%) from both water quality and economic points of view., 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 © 2025 Elsevier Ltd. All rights reserved.)

Objective: The 2017 McDonald criteria continued the separation of diagnostic criteria for relapsing-remitting multiple sclerosis (RRMS) and primary progressive MS (PPMS) for historical, rather than biological, reasons. We aimed to explore the feasibility of a single, unified set of diagnostic criteria when applied to patients with suspected PPMS., Methods: We retrospectively identified patients evaluated for suspected PPMS at 5 European centers. The 2017 McDonald PPMS criteria was the gold standard against which the 2017 McDonald RRMS dissemination in space (DIS) and dissemination in time criteria were evaluated. We also investigated modified RRMS DIS criteria, including: (i) optic nerve lesions; (ii) ≥2 spinal cord lesions; and (iii) higher fulfilment of DIS criteria alone (lesions in ≥3 regions) without dissemination in time/positive cerebrospinal fluid, for a diagnosis of PPMS., Results: A total of 282 patients were diagnosed with PPMS using the 2017 McDonald criteria, and 40 with alternate disorders. The 2017 McDonald RRMS DIS criteria and the modified DIS criteria including the optic nerve or ≥2 spinal cord lesions performed well in PPMS diagnosis when combined with dissemination in time/positive cerebrospinal fluid (sensitivity 92.9-95.4%, specificity 95%, accuracy 93.2-95.3%). A diagnosis of PPMS based on high fulfillment of modified RRMS DIS criteria had high specificity, but low sensitivity. A diagnostic algorithm applicable to patients evaluated for suspected MS is proposed., Interpretation: The 2017 McDonald RRMS criteria and modifications to DIS criteria, currently under consideration, performed well in PPMS diagnosis. Forthcoming revisions to the McDonald criteria should consider a single, unified set of diagnostic criteria for MS. ANN NEUROL 2025;97:571-582., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Objectives: The incidence of ischemic stroke in young adults has increased substantially. There are limited data in the literature concerning the short-term clinical outcome in young adults with acute stroke after revascularization treatment. Due to the lack of available data on gender differences short-term clinical outcome, we designed the present study., Materials and Methods: We collected data from 127 patients aged 50 years or younger consecutively admitted to the Stroke-Unit of "Cardarelli" Hospital in Naples between August 2017 and September 2022 due to ischemic stroke. All of them underwent thrombolysis and/or endovascular treatment., Results and Conclusions: Smoking, hypertension, and dyslipidemia emerged as the most prevalent risk factors. A gender-based analysis revealed that the history of stroke was the only statistically significant factor more frequently observed in the female group. The leading stroke etiology was "cardioembolism," succeeded by strokes of "other determined origin", "undetermined etiology," "large-artery atherosclerosis," and "small-artery occlusion." Concerning reperfusion therapy, intravenous thrombolysis ranked as the most utilized treatment, followed by "bridging" therapy (combining intravenous thrombolytic therapy with thrombectomy) and primary mechanical thrombectomy. Notably, the average NIHSS scores 7 days post-revascularization were lower among females compared to males, constituting a statistically significant distinction. Nevertheless, no statistically significant correlation surfaced between gender and treatment type in NIHSS mean values at admission, 2 hours, 24 hours post-revascularization, or 7 days post-revascularization. This suggests that the observed disparity in mean NIHSS score between male and female groups after 7 days may potentially stem from other factors, such as endogenous estrogens., Competing Interests: Declarations. Ethical approval: None. Conflict of interest: None. Informed consent: None., (© 2024. Fondazione Società Italiana di Neurologia.)

A strong interplay exists between sleep and dietary habits, and sleep disturbances have been repeatedly documented in individuals with eating disorders (EDs). The orexin system - implicated in sleep regulation, energy homeostasis, and food reward - may represent a mechanist link between sleep alterations and disordered eating behaviors. Daridorexant is a dual orexin receptor antagonist (DORA) recently approved for the treatment of insomnia, with demonstrated efficacy and tolerability. Owing to its action on orexin neurons, the compound represents an intriguing option for addressing both sleep-related and core symptoms of EDs. By inhibiting motor hyperactivity, daridorexant may reduce excessive physical exercise in individuals with anorexia nervosa (AN) restricting type. Additionally, the compound may exert anti-binge effects, suggesting broad applicability in binge ED, bulimia nervosa, and binge/purging AN. In this framework, daridorexant emerges as a promising therapeutic option, offering a multifaceted approach to improving circadian rhythms, energy balance, and overall quality of life in individuals with diverse ED subtypes., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Depressive disorders are disabling conditions that account for high social costs. Pilates demonstrated to have several beneficial effects on health. Objective of this manuscript was to systematically review the literature about the effects of Pilates on depressive disorders. A bibliographic search was conducted in the main database sources (Pubmed, Medline, and Scopus). The inclusion criteria consisted of articles written in English language about the effectiveness of Pilates on depressive symptoms. Most of included studies are randomized controlled trials (10 out of 12). The available literature agrees in indicating that Pilates is effective in improving depressive symptoms especially when compared to inactivity and when this practice is administered for a medium-long period (8-16 weeks). In addition, Pilates seems to have at least comparable effectiveness than aerobic exercise. Pilates can be considered a reliable complementary treatment for people with depressive disorders. These findings should be interpreted considering the different types of practice administered as well as the different duration of the programs or rating scales used to assess mood symptoms. Studies with a more homogenous design are needed to confirm and make generalizable the results presented in this review., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

This multicenter real-world analysis evaluated the efficacy of isatuximab, pomalidomide, and dexamethasone (IsaPd) in 51 patients with multiple myeloma (MM) who were refractory to daratumumab (Dara-R). The majority were under 70 years old (60.8%), predominantly female (56.9%), and heavily pretreated, with 74.5% being triple-class refractory (TCR); 32.1% of the 28 patients with cytogenetic data had high-risk abnormalities. The overall response rate (ORR) was 56.9%, including 3 patients with stringent complete response (sCR), 4 with CR, and 7 with very good partial response (VGPR). Neither age, number of prior therapies, TCR status, nor time from Dara refractoriness to IsaPd initiation significantly affected response rates. Median progression-free survival (PFS) was 5.8 months, with a 12-month PFS probability of 30.6%. Baseline hemoglobin (Hb) levels were a key predictor of PFS: patients with Hb < 11.8 g/L had a 3.5-fold increased risk of progression, with a median PFS of 4.6 months compared to 22 months in those with higher Hb. Median overall survival (OS) was 21.0 months, with a 12-month OS probability of 63.4%. Lower Hb levels (< 11 g/L) were associated with a tenfold increased risk of mortality. Among the 28 patients who underwent FISH analysis, while no significant difference in mortality risk was observed, those with high-risk cytogenetic abnormalities exhibited a nearly tenfold increased risk of disease progression. These results suggest that IsaPd offers a meaningful option for Dara-R patients, with Hb levels serving as a critical predictor of both PFS and OS. However, PFS remains modest, underscoring the need for novel combination therapies., (© 2025 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)

Despite improvements in diagnosis and treatment approaches, prostate cancer (PC) remains a leading cause of cancer-related death in men. PC progresses through various stages, mostly driven by androgen receptor signaling. However, after androgen deprivation therapies, in a significant portion of patients, several different molecular mechanisms contribute to the development of castration resistance. Delving deeply into the molecular landscape of castration-resistant PC, grasping the selective pressures exerted by therapies, and understanding the drivers of lineage plasticity is pivotal to prevent progression. Targeting genetic and epigenetic alterations that drive this transition will guide clinical management strategies and possibly prevent and/or treat lethal disease., Competing Interests: Disclosures G.N. Fanelli is supported by a fellowship from the American-Italian Cancer Foundation, United States (AICF) and by the Italian Ministry of University and Research—PON “Research and Innovation” 2014 to 2020 (PON R&I) Actions IV. 4 “PhD programmes and research contracts on innovation topics” P.V. Nuzzo is supported by the Prostate Cancer Foundation, United States. F. Pederzoli is supported by a fellowship from the AICF. M. Loda is supported by the National Cancer Institute, United States grants P50CA211024 and P01CA265768, the US Department of Defense, United States (DoD) Grant DoD PC160357, as well as the Prostate Cancer Foundation., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Carrots (Daucus carota L.) are a rich source of provitamin A, namely, α- and β-carotene. Breeding programs prioritize increasing β-carotene content for improved color and nutrition. Understanding the genetic basis of carotenoid accumulation is crucial for implementing genomic-assisted selection to develop high-carotenoid lines. While previous studies identified loci (Y2, Y, Or, and REC) associated with carrot color and carotenoid content, this study employed genome-wide association (GWA) in a diverse panel of 738 carrot accessions. We discovered a novel locus with a candidate gene encoding phytoene synthase, a key enzyme in carotenoid biosynthesis. The Y2, Y, Or, and REC loci are mostly fixed in orange varieties, yet considerable variation in carotenoid concentration persists. This suggests a multigenic trait influenced by the environment. GWA of carotenoid concentration identified a quantitative trait locus for total carotenoids and α-carotene. We explored the accuracy of genomic prediction (GP) models to predict carotenoid concentration. We determined the optimal number of plants and plots required for accurate carotenoid phenotyping, finding ≥5 plants per plot and three plots per site as the minimum effective sample per accession. GP models achieved accuracies ranging from 0.06 to 0.40 depending on the carotenoid measured and environment the carrots were assayed. Additional studies in breeding programs will clarify the potential of genomic-assisted selection for high-carotenoid carrots., (© 2025 The Author(s). The Plant Genome published by Wiley Periodicals LLC on behalf of Crop Science Society of America.)

Limited evidence exists about preserving neurovascular bundles during radical prostatectomy (RP) for high-risk prostate cancer (HRPCa) patients. Hence, we validated an existing algorithm predicting contralateral extraprostatic extension (cEPE) risk in unilateral high-risk cases. This algorithm aims to assist in determining the suitability of unilateral nerve-sparing RP. Among 264 patients, 48 (18%) had cEPE. The risk of cECE varied: 8%, 17.2%, and 30.8% for the low, intermediate, and high-risk groups, respectively. Despite a higher risk of cECE among individuals classified as low-risk in the development group compared to the validation group, our algorithm's superiority over always/never nerve-sparing RP was reaffirmed by decision curve analysis. Therefore, we conclude that bilateral excision may not always be justified in men with unilateral HRPCa. Instead, decisions can be based on our suggested nomogram., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: The data utilized in this study were derived from preexisting records and databases, and no novel data were solicited from patients for the purpose of this research. To safeguard privacy, all patient data underwent de-identification procedures. Patient identities were anonymized, and any personal information was meticulously managed to uphold confidentiality., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Factor V (FV) is a glycoprotein that plays a pivotal role in hemostasis, being involved in coagulant and anticoagulant pathways. Congenital FV deficiency is a rare bleeding disorder with an incidence of 1 per million live births, considering the most severe homozygous form. FV deficiency is diagnosed using routine coagulation tests and FV activity assays. Several mutations, including missense, nonsense, and frameshift, have been detected in the F5 gene. Clinical symptoms are variable, ranging from mild ecchymoses and mucosal bleeding to life-threatening intracranial hemorrhage. The mainstay of treatment includes fresh-frozen plasma, preferentially virus-inactivated. In this narrative review, we provide an update of the main laboratory, molecular, clinical, and therapeutic features of inherited FV deficiency., Competing Interests: None declared., (Thieme. All rights reserved.)

The ongoing mpox outbreak in sub-Saharan Africa has highlighted the critical need for equitable vaccine access and robust logistical support. However, these factors alone are insufficient to ensure the success of vaccination campaigns in regions characterized by unique epidemiological and immunological challenges. One significant issue is the high prevalence of helminth infections, which are known to impair immune responses to vaccines, potentially reducing both short-term efficacy and long-term antibody titers. This paper explores the implications of helminthiasis for mpox vaccination in sub-Saharan Africa, emphasizing the need for integrated strategies to address this co-infection. We discuss whether combining deworming programs with vaccination campaigns could enhance vaccine responses and examine the applicability of emerging data on single-dose mpox vaccination in the context of endemic helminth infections. Furthermore, we highlight the importance of real-time surveillance to monitor vaccine effectiveness and identify breakthrough infections in regions with high helminth prevalence. Our findings underscore the necessity of a context-specific approach to mpox vaccination policies, one that considers the intricate interplay between helminth infections and vaccine efficacy. Addressing these challenges is essential to ensure the success of vaccination efforts and to mitigate the broader public health impact of mpox in Africa and beyond.

Background and Objective: The integration of ultrafast Doppler imaging with singular value decomposition clutter filtering has demonstrated notable enhancements in flow measurement and Doppler sensitivity, surpassing conventional Doppler techniques. However, in the context of transthoracic coronary flow imaging, additional challenges arise due to factors such as the utilization of unfocused diverging waves, constraints in spatial and temporal resolution for achieving deep penetration, and rapid tissue motion. These challenges pose difficulties for ultrafast Doppler imaging and singular value decomposition in determining optimal tissue-blood (TB) and blood-noise (BN) thresholds, thereby limiting their ability to deliver high-contrast Doppler images., Methods: This study introduces a novel local blood subspace detection method that utilizes multilevel thresholding by the valley-emphasized Otsu's method to estimate the TB and BN thresholds on a pixel-based level, operating under the assumption that the magnitude of the spatial singular vector curve of each pixel resembles the shape of a trimodal Gaussian. Upon obtaining the local TB and BN thresholds, a weighted mask (WM) is generated to assess the blood content in each pixel. To enhance the computational efficiency of this pixel-based algorithm, a dedicated tree-structure k-means clustering approach, further enhanced by noise rejection (NR) at each singular vector order, is proposed to group pixels with similar spatial singular vector curves, subsequently applying local thresholding (LT) on a cluster-based (CB) level., Results: The effectiveness of the proposed method was evaluated using an ex-vivo setup featuring a Langendorff swine heart. Comparative analysis with power Doppler images filtered using the conventional global thresholding method, which uniformly applies TB and BN thresholds to all pixels, revealed noteworthy enhancements. Specifically, our proposed CBLT+NR+WM approach demonstrated an average 10.8-dB and 11.2-dB increase in Contrast-to-Noise ratio and Contrast in suppressing the tissue signal, paralleled by an average 5-dB (Contrast-to-Noise ratio) and 9-dB (Contrast) increase in suppressing the noise signal., Conclusions: These results clearly indicate the capability of our method to attenuate residual tissue and noise signals compared to the global thresholding method, suggesting its promising utility in challenging transthoracic settings for coronary flow measurement., 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 Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The nodal burden of patients with residual isolated tumor cells (ITCs) in the sentinel lymph nodes (SLNs) after neoadjuvant chemotherapy (NAC) (ypN0i+) is unknown, and axillary management is not standardized. We investigated rates of additional positive lymph nodes (LNs) at axillary lymph node dissection (ALND) and oncologic outcomes in patients with ypN0i+ treated with and without ALND., Methods: The Oncoplastic Breast Consortium-05/ICARO cohort study (ClinicalTrials.gov identifier: NCT06464341) retrospectively analyzed data from patients with stage I to III breast cancer with ITCs in SLNs after NAC from 62 centers in 18 countries. The primary end point was the 3-year rate of any axillary recurrence. The rate of any invasive recurrence was the secondary end point., Results: In total, 583 patients were included, of whom 182 (31%) had completion ALND and 401 (69%) did not. The median age was 48 years. Most patients (74%) were clinically node-positive at diagnosis and 41% had hormone receptor-positive/human epidermal growth factor receptor 2-negative tumors. The mean number of SLNs with ITCs was 1.2. Patients treated with ALND were more likely to present with cN2/3 disease (17% v 7%, P < .001), have ITCs detected on frozen section (62% v 8%, P < .001), have lymphovascular invasion (38% v 24%, P < .001), and receive adjuvant chest wall (89% v 78%, P = .024) and nodal radiation (82% v 75%, P = .038). Additional positive nodes were found at ALND in 30% of patients, but only 5% had macrometastases. The 3-year rates of any axillary and any invasive recurrence were 2% (95% CI, 0.95 to 3.6) and 11% (95% CI, 8 to 14), respectively, with no statistical difference by type of axillary surgery., Conclusion: The nodal burden in patients with ypN0(i+) was low, and axillary recurrence after ALND omission was rare in patients selected for this approach. These results do not support routine ALND in all patients with ypN0(i+).

Objectives: To estimate the risk of COVID-19-related hospitalization and death (CovH/D), among high-risk individuals early treated for COVID-19 and to identify associated factors., Methods and Results: A multicenter cohort of 12,475 high-risk outpatients (female 50.2%, median age 70 years [IQR 57-80], fully vaccinated 79.1%, immunocompromised 23.2%) treated with monoclonal antibodies or antivirals for mild-to-moderate COVID-19 (March 2021-May 2023) in the Lazio region, Italy. The unadjusted risk of CovH/D by Day 30 was 3.08% (95% CI 2.7%-3.4%). By means of logistic regression models, which included a specific set of potential confounders for each exposure of interest, we observed a higher risk for the elderly, unvaccinated and immunocompromised participants. Using the "Delta period" as a reference, a decreased risk was observed for Omicron waves., Conclusions: Despite the administration of COVID-19 early treatment and the decreasing risk of CovH/D across the calendar periods, the elderly, the unvaccinated and the immunocompromised people remain at high risk of clinical progression., (© 2024 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Purpose: Despite growing concerns about trends in cocaine use, there is a shortage of longitudinal research that prospectively examines risk and protective factors associated with cocaine initiation and use in general youth populations. This study addresses this gap., Methods: Growing Up in Ireland is a nationally representative cohort. Individual, family, and socio-environmental exposures associated with incident past-year cocaine use at ages 17 (N = 5965) and 20 (n = 4549) were assessed with survey-weighted logistic regression using generalised estimating equations. Prevalent past-year cocaine use at 20 (N = 4679) was analysed using generalised estimating equations complemented by gradient-boosted decision trees and Shapley explanations., Results: 221 (3.7%) self-reported cocaine use at 17 and 1072 (22.9%) at 20. Alcohol use at 14 or younger was associated with eight times the odds of cocaine use at 17 (aOR 8.0, 95% CI 1.7-37.3) and 19 times at 20 (aOR 19.2, 95% CI 8.6-43.2). Peer cannabis use was associated with 7 times the odds of cocaine use at 17 (aOR 7.3, 95% CI 2.9-18.3) and double at 20 (aOR 2.4, 95% CI 1.8-3.2). Growing up in a neighbourhood where substance use was common doubled the odds of cocaine use at 17 (aOR 2.4, 95% CI 1.3-4.4). Shapley explanations revealed individual-specific positive or negative impacts of exposures., Discussion: Cocaine use among 20-year-olds in Ireland is higher than reported internationally, and increases sharply between the ages of 17 and 20, suggesting a need for interventions targeting this age group. However, associations with early adolescent factors suggest that early interventions may also be important., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Antibodies to proteolipid protein-1 (PLP1-IgG), a major central myelin protein also expressed in the peripheral nervous system (PNS) as the isoform DM20, have been previously identified mostly in patients with multiple sclerosis (MS), with unclear clinical implications. However, most studies relied on nonconformational immunoassays and included few patients with non-MS CNS autoimmune demyelinating disorders (ADDs). We aimed to investigate conformational PLP1-IgG in the whole ADD spectrum., Methods: We devised a new live cell-based assay (CBA) for PLP1-IgG and used it to test 2 cohorts (retrospective exploratory, n = 284; prospective validation, n = 824) of patients with ADDs and controls (n = 177). Patients were classified as MS, neuromyelitis optica spectrum disorders (NMOSDs), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and other ADDs. PLP1-IgG-positive samples were tested for IgG subclasses, DM20-IgG, and on rat brain tissue-based assay (TBA). Complement-dependent cytotoxicity (CDC) was assessed on a live CBA and antigen specificity and conformational binding through immunoadsorption/colocalization/fixation experiments., Results: PLP1-IgG were found in 0 of 177 controls and 42 of 1104 patients with ADDs mainly diagnosed as other ADDs (19/42) with frequent myelitis/encephalomyelitis (14/19) and coexisting PNS involvement (13/19). Four of 19 patients with other ADDs fulfilled the seronegative NMOSD criteria. PLP1-IgG were also found in patients with MOGAD (11/42), more frequently with PNS involvement ( p = 0.01), and in patients with MS (12/42), more frequently with atypical features ( p < 0.001). PLP1-IgG-positive MOGAD had higher EDSS scores ( p < 0.001) and PLP1-IgG-positive MS had higher severity scores (MSSS, p < 0.001) compared with those PLP1-IgG-negative. Overall, PLP1-IgG were found in 24.1% of patients with CNS+PNS-ADD, 21.2% with atypical MS, 8.3% with MOGAD, 12.0% with seronegative NMOSD, and 1.4% with typical MS. Their frequency within each diagnostic subgroup was consistent between the exploratory and validation cohorts. PLP1-IgG a) colocalized with their target on CBA-TBA, where their binding was abolished after immunoadsorption and fixation-induced conformational epitope alteration; b) mostly pertained to the IgG1/IgG3 subclass (68.3%) and were able to induce CDC; and c) coreacted with DM20 in all 12 patients with PNS involvement tested., Discussion: Conformational PLP1-IgG predominantly identify patients with non-MS ADDs. They should be tested mainly in those with CNS + PNS ADD, coherently with DM20-IgG coreactivity. PLP1-IgG could also be investigated as disease modifiers and prognostic markers in MS and MOGAD. Preliminary evidence supports their pathogenic potential.

When asked what differentiates the Milan Approach now from the period when Luigi Boscolo and Gianfranco Cecchin were alive, the teachers at Via Leopardi remain humble. This article aims to explore the current identity of the Milan Approach. What is now the specificity of the Milan model? Do we have particularities that differentiate us from other clinical or therapeutic models? We still work according to the notion of the observing system, and we apply the three directives of the 1980s: hypothesizing, circularity, and curiosity. Is there a specific direction in which our approach is heading? Rather than attempting to take a picture of a status quo, this article seeks to represent the questions and doubts that organize a constant process in progress-as clinical work usually is. In this article, we wish to underline some aspects that are important to us and that we hold dear. We assert that the premises we have in common allow us to be flexible enough to keep in tune with current events and to address social issues that are of political relevance, in order to adapt to cultural changes., (© 2024 Family Process Institute.)