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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.)

Background: Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents., Objectives: We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics., Design: This is a retrospective real-world cohort study of BRAF V600E mutated mCRC patients treated with second-line EC ± B at 20 Italian centres., Methods: Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients., Results: A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases ( p  = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR ( p  = 0.005) and a lower rate of ETS ( p  = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR) DpR   ⩾ 30% : 0.52, 95% CI: 0.30-0.90, p  = 0.02) and median cut-off values (HR DpR⩾15% : 0.55, 95% CI: 0.33-0.92, p  = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78-0.98, p  = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR ( p DpR⩾30%  = 0.04; p DpR⩾15%  = 0.04; p cont.  = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected., Conclusion: A DpR of at least 15% independently predicts PFS benefit in BRAF V600E mutated mCRC patients treated with second-line EC ± B., Competing Interests: L. S. reported current support by the Associazione Italiana per la Ricerca sul Cancro (AIRC) under My First Grant (MFAG) No. MFAG27367 and consulting or advisory role for Pierre-Fabre, AstraZeneca, Bayer, SERVIER, Merck, Amgen, GSK, Incyte, Leopharma, MSD, Takeda. F. P. reported institutional research grants from BMS, Incyte, Agenus, Amgen, Lilly and AstraZeneca, and personal fees from BMS, MSD, Amgen, Merck-Serono, Pierre-Fabre, Servier, Bayer, Takeda, Astellas, Johnson&Johnson, Rottapharm, Ipsen, AstraZeneca, GSK, Daiichi-Sankyo, Seagen/Pfizer, Beigene. S. L. reported consulting or advisory roles for Amgen, Merck Serono, Eli Lilly, AstraZeneca, Incyte, Daiichi-Sankyo, Bristol Myers Squibb, Servier, Merck Sharp & Dohme, Astellas, and Takeda; is on the speakers’ bureau for Roche, Eli Lilly, Bristol Myers Squibb, Servier, Merck Serono, Pierre Fabre, GlaxoSmithKline, and Amgen; research funding from Amgen, Merck Serono, Bayer, Roche, Lilly, AstraZeneca, and Bristol-Myers Squibb. L. N. reported advisory board/honoraria from Astra-Zeneca, Pierre-Fabre, Bayer and travel grants from Astra-Zeneca, MSD. C. C. reported honoraria from Amgen, Bayer, Merck, Merck, MSD, Pierre Fabre, Roche, and Servier; consulting or advisory roles for Amgen, Bayer, MSD, Nordic Bioscience, Pierre Fabre, and Roche; is on the speakers’ bureau for Merck, Pierre Fabre, Servier; research funding from Bayer, Merck, Roche, and Servier. All other authors have declared no conflicts of interest., (© The Author(s), 2025.)

Background: Few data are available on polymer-free drug-eluting stents in patients undergoing percutaneous coronary intervention (PCI)., Aims: We aimed to determine the efficacy and safety of a polymer-free amphilimus-eluting stent (AES), using a reservoir-based technology for drug delivery, compared with a biodegradable-polymer everolimus-eluting stent (EES)., Methods: This was a randomised, investigator-initiated, assessor-blind, non-inferiority trial conducted at 14 hospitals in Italy (ClinicalTrials.gov: NCT04135989). All-comer patients undergoing PCI were randomly assigned to either polymer-free AES or biodegradable-polymer EES. The primary endpoint was a device-oriented composite endpoint, including cardiovascular death, target vessel myocardial infarction, or target lesion revascularisation at 1-year follow-up., Results: Between January 2020 and June 2022, a total of 2,107 patients with 3,042 coronary lesions were randomised to polymer-free AES (1,051 patients) or biodegradable-polymer EES (1,056 patients). At 1-year follow-up, the primary endpoint occurred in 86 (8.2%) patients randomised to polymer-free AES and 76 (7.2%) patients randomised to biodegradable-polymer EES (risk difference 1%, upper limit of the 1-sided 95% confidence interval [CI] of 2.9%; p for non-inferiority=0.041). There were no significant differences in the incidence of the components of the primary endpoint between groups. However, definite or probable stent thrombosis occurred more frequently in patients randomised to polymer-free stents (1.0% vs 0.3%; hazard ratio 3.72, 95% CI: 1.04-13.33; p=0.044) due to an increased risk of early stent thrombosis within 30 day Conclusions: In all-comer patients undergoing PCI, polymer-free AES were non-inferior to biodegradable-polymer EES at 1-year follow-up in terms of a device-oriented composite endpoint despite being associated with an increased risk of early stent thrombosis.

This clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions was developed in association with the European Society of Cardiology Working Group on Cardiovascular Surgery. It aims to define procedural and contemporary technical requirements that may improve the efficacy and safety of percutaneous coronary intervention (PCI), both in the acute phase and at long-term follow-up, in a high-risk cohort of patients on optimal medical therapy when clinical and anatomical high-risk criteria are present that entail unacceptable surgical risks, precluding the feasibility of coronary artery bypass grafting (CABG). This document pertains to patients with surgical contraindication according to the Heart Team, in whom medical therapy has failed (e.g., residual symptoms), and for whom the Heart Team estimates that revascularisation may have a prognostic benefit (e.g., left main, last remaining vessel, multivessel disease with large areas of ischaemia); however, there is a lack of data regarding the size of this patient population. This document aims to guide interventional cardiologists on how to proceed with PCI in such high-risk patients with reduced left ventricular ejection fraction after the decision of the Heart Team is made that CABG - which overall is the guideline-recommended option for revascularisation in these patients - is not an option and that PCI may be beneficial for the patient. Importantly, when a high-risk PCI is planned, a multidisciplinary decision by interventional cardiologists, cardiac surgeons, anaesthetists and non-invasive physicians with expertise in heart failure management and intensive care should be agreed upon after careful consideration of the possible undesirable consequences of PCI, including futility, similar to the approach for structural interventions.

Background/Objectives : Psoriasis is a chronic inflammatory skin disease that may have a significant impact on patients' quality of life. Alongside clinical scores, treatment goals include improvements in patients' quality of life, divided into its social, working and psychosocial life aspects. Indeed, psychological impairment should always be considered in the management of moderate-to-severe psoriasis. Tildrakizumab, an anti-IL-23, is approved for the management of moderate-to-severe psoriasis. Both clinical trials and real-life studies show its efficacy and safety; however, no studies have evaluated how tildrakizumab may improve different domains of quality of life, including physical, psychological, and social aspects of patients' quality of life. The objective was to evaluate the effectiveness of tildrakizumab in the management of moderate-to-severe psoriasis, focusing on the impact on all domains of patients' quality of life. Methods : A 28-week multicenter, real-life, retrospective study was performed enrolling patients affected by moderate-to-severe psoriasis undergoing treatment with tildrakizumab. PASI and DLQI were evaluated at each follow-up (W16, W28). A sub-analysis of each DLQI question evaluated different domains of quality of life, including physical, psychological, and social aspects of patients' quality-of-life. Results : A total of 62 patients were enrolled. At week 28, 97.1%, 85.7%, and 54.3% of patients achieved PASI75, PASI90, and PASI100, respectively. DLQI showed a significant reduction from baseline (20.3 ± 5.5) to week 28 (0.9 ± 2.2, p < 0.0001), with up to 82.9% achieving DLQI < 1. Sub-analysis of each question (Q1-Q10) showed a reduction in the value of each answer from baseline to week 28. Conclusions : The results confirm tildrakizumab as an effective and safe treatment in real life, positively affecting all domains of quality of life, with significant impact already appreciable at week 16 of follow-up.

Background: Advancing the retrograde microcatheter (MC) into the antegrade guide catheter during retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) can be challenging or impossible, preventing guidewire externalization., Objectives: To detail and evaluate all the techniques focused on wiring to achieve intubation of the distal tip of a microcatheter, balloon, or stent with an antegrade or retrograde guidewire, aiming to reduce complications by minimizing tension on fragile collaterals during externalization and enabling rapid antegrade conversion in various clinical scenarios., Methods: We describe the two main techniques, tip-in and rendezvous, and their derivatives such a facilitated tip-in, manual MC-tip modification, tip-in the balloon, tip-in the stent, deep dive rendezvous, catch-it and antegrade microcatheter probing. We provide case studies that demonstrate the effectiveness of these techniques in complex scenarios involving extreme vessel angulation, severe calcification, fragile collaterals, and challenging retrograde MC crossing without externalization., Conclusion: The development of advanced variants along with traditional techniques to establish retrograde guidewire connection and antegrade conversion has led to the establishment of a cohesive group of methods known as portal techniques. These approaches serve as strategic advantages in retrograde CTO-PCI, providing a valuable and feasible alternative to conventional retrograde connection techniques, particularly when those techniques fail. Their ability to avoid the externalization process reduces potential damage to collateral channels and the ostium of the donor artery, potentially leading to a reduction in complication rates., (© 2024 he Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: When considering whether a patient is fit for surgery, a comprehensive patient assessment represents the first step for an anaesthetist to evaluate the risks associated with the procedure and the patient's underlying diseases, and to optimise (whenever possible) the perioperative surgical journey. These guidelines from the European Society of Anaesthesiology and Intensive Care Medicine (ESAIC) update previous guidelines to provide new evidence on existing and emerging topics that consider the different aspects of the patient's surgical path., Design: A comprehensive literature review focused on organisation, clinical facets, optimisation and planning. The methodological quality of the studies included was evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology. A Delphi process agreed on the wording of recommendations, and clinical practice statements (CPS) supported by minimal evidence. A draft version of the guidelines was published on the ESAIC website for 4 weeks, and the link was distributed to all ESAIC members, both individual and national, encompassing most European national anaesthesia societies. Feedback was gathered and incorporated into the guidelines accordingly. Following the finalisation of the draft, the Guidelines Committee and ESAIC Board officially approved the guidelines., Results: In the first phase of the guidelines update, 17 668 titles were initially identified. After removing duplicates and restricting the search period from 1 January 2018 to 3 May 2023, the number of titles was reduced to 16 774, which were then screened, yielding 414 abstracts. Among these, 267 relevant abstracts were identified from which 204 appropriate titles were selected for a comprehensive GRADE analysis. Additionally, the study considered 4 reviews, 16 meta-analyses, 9 previously published guidelines, 58 prospective cohort studies and 83 retrospective studies. The guideline provides 55 evidence-based recommendations that were voted on by a Delphi process, reaching a solid consensus (>90% agreement)., Discussion: This update of the previous guidelines has covered new organisational and clinical aspects of the preoperative anaesthesia assessment to provide a more objective evaluation of patients with a high risk of postoperative complications requiring intensive care. Telemedicine and more predictive preoperative scores and biomarkers should guide the anaesthetist in selecting the appropriate preoperative blood tests, x-rays, and so forth for each patient, allowing the anaesthetist to assess the risks and suggest the most appropriate anaesthetic plan., Conclusion: Each patient should have a tailored assessment of their fitness to undergo procedures requiring the involvement of an anaesthetist. The anaesthetist's role is essential in this phase to obtain a broad vision of the patient's clinical conditions, to coordinate care and to help the patient reach an informed decision., (Copyright © 2024 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Pretreatment with a P2Y 12 inhibitor may be considered in patients with ST-segment elevation myocardial infarction (STEMI) referred to percutaneous coronary intervention (PCI). Intravenous cangrelor is an alternative in this setting, where oral absorption can be hindered. The aim of this study was to compare cangrelor administered after coronary angiography (i.e., "downstream") and ticagrelor pretreatment (i.e., "upstream")., Methods: STEMI patients undergoing PCI from October 2019 to June 2023 were included. The primary outcome was the composite of in-hospital major adverse cardiovascular events (MACE). Secondary outcomes included individual components of the primary outcome and in-hospital major bleeding. Univariable and multivariable regression analyses were performed in unmatched and propensity-matched cohorts., Results: Of 6086 patients enrolled in the prospective CAST registry, 761 were included: 383 (50.3 %) received downstream cangrelor and 378 (49.7 %) upstream ticagrelor. In the matched population, no between-group differences were observed in MACE (odds ratio [OR] 1.30; 95 % confidence interval [CI] 0.79-2.17; P 0.308), all-cause death (OR 1.91; 95 % CI 0.87-4.54; P 0.124), myocardial infarction (OR 2.64; 95 % CI 0.76-12.14; P 0.154), stent thrombosis (OR 0.38; 95 % CI 0.06-1.80; P 0.255), unplanned repeat revascularization (OR 1.22; 95 % CI 0.32-4.98; P 0.766) and major bleeding (OR 0.98; 95 % CI 0.50-1.93; P 0.955). Cardiogenic shock and bailout administration of glycoprotein IIb/IIIa inhibitors were independent predictors of MACE, while radial access showed an inverse association with the primary outc., Conclusions: In P2Y 12 -naïve STEMI patients undergoing primary PCI, no significant differences were noted in the risk of in-hospital ischemic and bleeding events between downstream cangrelor and upstream ticagrelor., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: Cangrelor, the only intravenous platelet P2Y 12 receptor inhibitor, is characterized by a prompt and potent platelet inhibition, with a rapid offset of action. Large-scale clinical trials have shown that cangrelor reduce peri-procedural thrombotic events among patients undergoing percutaneous coronary interventions and not pre-treated with an oral P2Y 12 receptor inhibitor. However, high P2Y 12 receptor occupancy provided by cangrelor raises concerns for drug-drug interactions (DDIs) when transitioning to oral P2Y 12 inhibitors., Areas Covered: An understanding of the pharmacology of cangrelor and oral P2Y 12 inhibitors is essential to define the optimal approach to transition to oral P2Y 12 inhibitors without incurring the risk of DDIs. This review, based on a thorough literature search in major scientific databases (PubMed, Cochrane Library, Web of Science), synthesizes the pharmacology of cangrelor and the oral P2Y 12 receptor inhibitors, providing the rationale for the occurrence of DDIs and strategies to avoid such risk., Expert Opinion: The timing of transition from cangrelor to oral P2Y 12 inhibitors plays a crucial role in the occurrence of DDIs, especially with clopidogrel and prasugrel. Currently, no evidence suggests a DDI when transitioning to ticagrelor. Adhering to product labels and guideline recommendations is crucial for optimizing safety and efficacy of cangrelor.

Background: The latest meta-analysis indicated potential survival benefits from ultra-short-acting β-blockers in patients with sepsis with persistent tachycardia. However, subsequent multicenter randomized controlled trials (RCTs) have reported conflicting findings, prompting the need for an updated meta-analysis to incorporate these newly published RCTs., Research Question: Does the use of ultra-short-acting β-blockers (esmolol or landiolol) in patients with sepsis with persistent tachycardia improve mortality?, Study Design and Methods: We conducted an updated systematic search through April 2, 2024, exploring the MEDLINE, Cochrane Central Register of Controlled Trials, and Embase databases for RCTs reporting mortality in adult patients with sepsis treated with esmolol or landiolol as compared with those treated with neither of these or receiving placebo and published in English. Meta-analyses were conducted with the random effects model. The primary outcome was mortality at the longest follow-up, with subgroup analysis separating single-center RCTS from large multicenter RCTs., Results: Eight RCTs (885 patients) were included in the primary analysis. Ultra-short-acting β-blockers did not improve mortality significantly at the longest follow-up (risk ratio, 0.84; 95% CI, 0.68-1.02; P = .08; I 2  = 51%; very low certainty of the evidence) and 28-day mortality (risk ratio, 0.77; 95% CI, 0.59-1.00; P = .05; I 2  = 62%). Subgroup analyses of mortality outcomes pointed toward different results between single-center and multicenter RCTs. Trial sequence analyses showed that both mortality outcomes were not robust. The sensitivity analyses suggested a significant reduction in mortality by adding RCTs published in non-English languages., Interpretation: In this updated meta-analysis, the use of esmolol or landiolol did not reduce mortality in patients with sepsis with persistent tachycardia. However, results were not robust and outcomes differed between single-center and multicenter RCTs. Moreover, sensitivity analyses showed the fragility of the primary outcome. Further studies regarding ultra-short-acting β-blockers with advanced cardiac monitoring or serial echocardiography are warranted., Trial Registry: International Prospective Register of Systematic Reviews; No.: CRD42024503570; URL: https://www.crd.york.ac.uk/prospero/., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Copyright © 2024 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Patients with esophageal cancer and concomitant liver cirrhosis (LC) pose a surgical challenge because of the increased risk of postoperative complications and mortality. Purpose of this study was to review the existing literature and estimate perioperative short-term outcomes of esophagectomy in this patient population. Systematic review and meta-analysis. PubMed, MEDLINE, Scopus, Web of Science, Cochrane Central Library, and ClinicalTrials.gov were queried. The search was last updated on July 30th, 2024. Primary outcomes were anastomotic leak (AL) and 90 day mortality. Ten observational studies were included for a total of 387 patients with LC. The age of the included patients ranged from 35 to 85 years, 91.2% were males. The main causes of liver cirrhosis were alcoholic (75%) and viral hepatitis (20.4%). Esophageal squamous cell carcinoma was diagnosed in 58.7% of patients. Ivor-Lewis esophagectomy with intrathoracic anastomosis was reported in 69.9% of patients, while McKeown esophagectomy with cervical anastomosis was reported in 30.1% of patients. The estimated pooled prevalence of AL and 90-day mortality were 13% (95% CI = 6-24%; I 2  = 72%) and 17% (95% CI = 10-27%; I 2  = 72%), respectively. The estimated pooled prevalence of postoperative pulmonary complication, sepsis, and liver failure were 52% (95% CI = 39-65%), 30% (95% CI = 14-52%), and 9% (95% CI = 4-17%), respectively. Esophagectomy can be performed in properly selected patients with LC and concomitant esophageal cancer. Foregut surgeons should be aware of the not negligible postoperative complications rates and mortality. Risk stratification and attentive perioperative care are essential to minimize serious adverse events., Competing Interests: Declarations. Conflict of interest: All the authors declare no conflict of interest. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with human participants or animals performed by any of the authors. Informed consent: Informed consent does not apply. Research involving human participants and/or animals: This project does not involve any new studies with human participants or animals conducted by any of the authors., (© 2024. Italian Society of Surgery (SIC).)