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Summary: Drosophila and its parasitoids provide an ecologically relevant model for studying host-parasitoid biology, focusing on the behavioral and physiological responses involved in host defensive strategies and parasitoid countermeasures. Here, we outline a protocol for rearing Pachycrepoideus, a pupal parasitoid wasp, and a behavioral assay to assess the long-term impact of parasitoid exposure on adult Drosophila. We detail the steps for preparing and cohabiting Drosophila with the wasps, documenting egg-laying, and analyzing reproductive responses and eclosion in fruit flies.For complete details on the use and execution of this protocol, please refer to Sadanandappa et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: Environmental factors influence an organism’s reproductive ability by regulating germline development and physiology. While the reproductive adaptations in response to extrinsic stress cues offer fitness and survival advantages to individuals, the mechanistic understanding of these modifications remains unclear. Here, we find that parasitoid wasps’ stress signaling regulates Drosophila melanogaster oogenesis. We show that fruit flies dwelling in the wasp-infested area elevate their fecundity, and the observed reproductive response is specific to Pachycrepoideus sp., a pupal parasitoid wasp. Pachycrepoideus-specific olfactory and visual cues recruit the signaling pathways that promote germline stem cell proliferation and accelerate follicle development, increasing egg production in Drosophila females. Downregulation of signaling engaged in oocyte development by shifting flies to a non-wasp-infested environment increases apoptosis of the developing follicles. Thus, this study establishes host germline responsiveness to parasitoid-specific signals and supports a predator strategy to increase hosts for infection.

Summary: Interaction domains in Drosophila chromosomes form by segregation of active and inactive chromatin in the absence of CTCF loops, but the role of transcription versus other architectural proteins in chromatin organization is unclear. Here, we find that positioning of RNAPII via transcription elongation is essential in the formation of gene loops, which in turn interact to form compartmental domains. Inhibition of transcription elongation or depletion of cohesin decreases gene looping and formation of active compartmental domains. In contrast, depletion of condensin II, which also localizes to active chromatin, causes increased gene looping, formation of compartmental domains, and stronger intra-chromosomal compartmental interactions. Condensin II has a similar role in maintaining inter-chromosomal interactions responsible for pairing between homologous chromosomes, whereas inhibition of transcription elongation or cohesin depletion has little effect on homolog pairing. The results suggest distinct roles for cohesin and condensin II in the establishment of 3D nuclear organization in Drosophila. : Using Hi-C analyses, Rowley et al. show that Drosophila genes form loops between the TSS and TTS, which in turn interact to form compartmental domains. Cohesin and condensin act in opposite ways on the formation of gene loops and domains. Keywords: CTCF, transcription, compartment, TAD, pairing, transvection, loop, Hi-C, HiChIP

Background: Pazopanib is part of the therapeutic armamentarium for the treatment of patients with advanced non-adipocytic soft tissue sarcomas (STS) who have received prior chemotherapy, but its optimal use in STS histologies is still left to be further defined., Design and Methods: Data on STS patients treated with pazopanib in Italy have been prospectively collected from July 2013 to December 2019 through a drug monitoring registry managed by the Italian Medicines Agency (AIFA). This nationwide observational cohort study included patients with advanced STS who received pazopanib. Clinicians were mandatorily requested to fill in the AIFA monitoring registry in order to prescribe pazopanib. Patients were recorded on the basis of their clinical characteristics, histological subtype captured at the time of treatment start, and clinical outcome. Primary outcome was time to treatment discontinuation (TTD). Secondary outcomes recorded were frequency of dose reduction and time to first dose reduction., Results: We analyzed data from 1964 sarcoma patients. The most represented histological subtypes were leiomyosarcoma (44.7%), undifferentiated sarcomas/not otherwise specified (11.5%), and synovial sarcoma (8.1%). Overall, the median TTD was 106 days. The variables significantly associated to shorter TTD were Eastern Cooperative Oncology Group performance status (1-2 versus 0), the number of previous lines of treatment (2-4 versus 0-1) and prescribed dose (200 mg or 400 mg versus 800 mg, all once daily). Among the most represented (>20 patients) histological subtypes, we also observed longer TTD in patients with histological diagnosis of malignant solitary fibrous tumor if compared with undifferentiated sarcoma not otherwise specified., Conclusions: In this nationwide observational real-world study, the outcomes are similar to those reported in the pivotal trial (PALETTE study). Our study includes a significant number of patients with rare/ultra-rare sarcoma subtypes and underlines possible differences in treatment duration among these histologies., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The CTO-ARC (Chronic Total Occlusion Academic Research Consortium) recognized that a nonstandardized definition of chronic total occlusion (CTO) percutaneous coronary intervention approaches can bias the complications' attribution to each crossing strategy., Objectives: The study sought to describe the numbers, efficacy, and safety of each final CTO crossing strategy according to CTO-ARC recommendations., Methods: In this cross-sectional study, data were retrieved from the European Registry of Chronic Total Occlusions between 2021 and 2022., Results: Out of 8,673 patients, antegrade and retrograde approach were performed in 79.2% and 20.8% of cases, respectively. The antegrade approach included antegrade wiring and antegrade dissection and re-entry, both performed with or without retrograde contribution (antegrade wiring without retrograde contribution: n = 5,929 [68.4%]; antegrade wiring with retrograde contribution: n = 446 [5.1%]; antegrade dissection and re-entry without retrograde contribution: n = 353 [4.1%]; antegrade dissection and re-entry with retrograde contribution: n = 137 [1.6%]). The retrograde approach included retrograde wiring (n = 735 [8.4%]) and retrograde dissection and re-entry (n = 1,073 [12.4%]). Alternative antegrade crossing was associated with lower technical success (70% vs 86% vs 93.1%, respectively; P < 0.001) and higher complication rates (4.6% vs 2.9% vs 1%, respectively; P < 0.001) as compared with retrograde and true antegrade crossing. However, alternative antegrade crossing was applied mostly as a rescue strategy (96.1%)., Conclusions: The application of CTO-ARC definitions allowed the reclassification of 6.7% of procedures as alternative antegrade crossing with retrograde or antegrade contribution which showed higher MACCE and lower technical success rates, as compared with true antegrade and retrograde crossing., Competing Interests: Funding Support and Author Disclosures Dr Bufe has received speaker honoraria from Biotronik and Shockwave Medical. Dr Pyxaras has received consulting/speaker/proctorship honoraria from Abiomed, AstraZeneca, Asahi Intecc, Biotronik, Boston Scientific, and Terumo. Dr Ladwiniec has received consulting/speaker/proctoring honoraria from Abbott, Biotronik, Boston Scientific, Cordis, Shockwave Medical, and SMT. Dr Werner has received speaker honoraria from Abbott, Asahi Intecc, OrbusNeich, Philips, Siemens, and Terumo. Dr Mashayekhi has received consulting/speaker/proctoring honoraria from Abbott, Abiomed, Asahi Intecc, AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi-Sankyo, Medtronic, OrbusNeich, Shockwave Medical, Teleflex, and Terumo. Dr Ayoub has received consultant/proctor honoraria from Boston Scientific, Teleflex, Asahi Intecc, Cordis, Terumo, and SIS Medical. Dr Goktekin has received consulting/speaker/proctoring honoraria from Boston Scientific, Medtronik, MicroPort, and Asahi Inc. Dr Agostoni has received consulting honoraria from Abbott, Boston Scientific, Cordis, iVascular, Medtronic, Neovasc, Seven Sons, Teleflex, and Terumo. Dr Diletti has received consultant/proctoring honoraria from Asahi Intecc, Terumo, IMDS, Boston Scientific, Teleflex, and Philips. Dr Rathore has received honoraria for speaker and proctoring from Abbott Vascular and Translumina Therapeutics. Dr Bozinovic has served as a speaker or proctor and/or received honoraria from Orbus Neich and Medtronic. Dr Galassi has received consulting/speaker honoraria from Asahi Intecc and Ivascular. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: For patients with aortic root dilatation and a structurally normal aortic valve (AV) undergoing composite aortic valve-graft (Bentall-De Bono) versus valve-sparing aortic root replacement (VSARR) procedures there are conflicting data regarding early and long-term benefits. We undertook a study-level meta-analysis to compare the results of both procedures., Methods: Three databases were assessed, and both randomized trials and observational studies were considered eligible. Kaplan-Meier curves of long-term survival and reoperation risk were reconstructed and compared with Cox linear regression and incidence rate ratios (IRR) with 95 % confidence intervals (CI). Landmark analysis and time-varying hazard ratio (HR) were analyzed. Odds ratios (OR) were calculated for early mortality, postoperative stroke, and re-exploration for postoperative bleeding. A random effects model was used. Sensitivity analyses included leave-one-out-analysis, meta-regression and subgroups analysis., Results: 1456 articles were identified, including 39 observational studies, totaling 14,651 patients (Bentall-De Bono = 9557 and VSARR = 5094). Twelve studies were adjusted. The mean weighted follow-up was 5.05 ± 3.7 years. VSARR was associated with significantly greater survival (HR = 0.50; 95 % CI, 0.45-0.57; p < 0.0001) at 15-year follow-up. The reoperation risk was higher following VSARR (HR = 1.30; 95 % CI, 1.03-1.63; p = 0.02.), although time-varying HR model and landmark analysis reported an increased risk of reoperation within 5 years after VSARR (HR = 1.57; 95 % CI, 1.23-2.01; p < 0.001), after which the difference disappeared. Subgroups analysis of studies excluding aortic dissection showed a comparable rate of late reoperation., Conclusions: VSARR is associated with improved long-term survival compared to Bentall-De Bono. The risk of late reoperation is higher within 5 years following VSARR, after which the two procedures are comparable., Competing Interests: Declaration of competing interest Non declared., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The clinical governance of patients with acute myocardial infarction (AMI) has markedly changed in the last few years. We sought to assess the contemporary in-hospital management patterns of patients with AMI at a country level., Methods: EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units)-2 was a nationwide, prospective registry aimed to evaluate the current management of patients admitted to intensive cardiac care units (CCUs) for an AMI in Italy., Results: Over a 4-week period (February 1st-29th, 2024), 183 CCUs enrolled 2806 consecutive patients: 52.6 % with non-ST elevation myocardial infarction (NSTEMI) and 47.4 % with ST-elevation myocardial infarction (STEMI). The median time from hospital admission to angiography in NSTEMI was 22.3 h (IQR 10.9-46.1), while for STEMI was 1.1 h (IQR 0.5-2.2) with significant difference between hospitals with and without catheterization laboratories. In both NSTEMI and STEMI patients, percutaneous coronary intervention (PCI) was the preferred management strategy (73.3 % and 94.2 %, respectively). An optimal secondary prevention therapy, including dual antiplatelet therapy, inhibition of the renin-angiotensin system, a beta-blocker and a high-intensity statin was prescribed at discharge in more than 75 % of patients with AMI. In-hospital major bleedings occurred in 2.0 % and 2.3 % (p = 0.58), while death in 1.8 % and 2.8 % (p = 0.09) of NSTEMI and STEMI patients, respectively., Conclusions: The EYESHOT-2 registry shows the current management strategies and outcome of AMI patients admitted to Italian CCUs and provides insights to improve the clinical care of such patients., Clinical Trial Registration: URL: http://www., Clinicaltrials: gov. Unique identifier: NCT06316128., Competing Interests: Declaration of competing interest LDL received honoraria for advisory boards or as speaker/chairman at scientific congresses from the following companies: Amgen, Aspen, AstraZeneca, Bayer, Boehringer Ingelheim, Chiesi, Daiichi Sankyo, Menarini, Novonordisk, Pfizer/Bristol-Myers Squibb, Sanofi and Servier. APM received personal fees for participation in study committees sponsored by Bayer, AstraZeneca, Novartis and Sanofi, outside the present work. SL received honoraria for advisory boards or as speaker/chairman at scientific congresses from the following companies: AstraZeneca, Boehringer Ingelheim, Chiesi, Daiichi Sankyo, Novonordisk, Pfizer/Bristol-Myers Squibb, and Sanofi. DL is an employee of Heart Care Foundation which conducted the study, partially supported by an unresctricted grant of research from Chiesi Farmaceutici S.p.A., Italy. MMG has no conflict of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Pregnancy-Associated Spontaneous Coronary Artery Dissection (P-SCAD) is the most common cause of myocardial infarction in pregnancy and postpartum. Aim of this systematic review is to provide a descriptive picture of P-SCAD presentation, clinical course, management and outcomes., Methods: International databases were systematically screened up to November 2023 and all published P-SCAD case reports/series identified; additionally, we gathered four original cases, establishing a new database for the derived cohort., Results: 253 studies (215 case reports, 38 case series) were included for the analysis, enrolling 316 patients admitted between 1952 and 2023. Median age was 34 (SD 5) years old, 64 (20.4 %) were prepartum, 249 (79.6 %) postpartum. Most common presentation was ST-elevation myocardial infarction (72.6 %). Cardiac arrest and cardiogenic shock occurred in 18.4 % and 16.1 %, respectively. Multivessel dissection was present in 45.2 % of cases, with left anterior descending artery being most frequently affected (74.4 %). Initial therapeutic strategy was medical therapy in 54.8 % while upfront revascularization was performed in 45.2 % of cases. Excluding autoptic studies, mortality rate was 4.1 %, without significant differences between pre and postpartum SCAD (p-value 0.6) or according to initial therapeutic approach (p-value 0.5). Recurrences after index event were registered in 74 patients (23.4 %), being more common after medical treatment than in case of immediate revascularization (30.8 versus 18.3 %, p-value 0.02)., Conclusions: P-SCAD is a complex clinical scenario: timely diagnosis is difficult, therapeutic management not well-defined, rate of recurrences not negligible. Additional observational studies and dedicated registries are necessary to enhance the management of this rare but severe condition., Competing Interests: Declaration of competing interest None declared., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The optimal strategy during percutaneous coronary intervention (PCI) of aneurysmatic right coronary artery (ARCA) remains uncertain and has never been tested in the acute setting., Objectives: To compare the in-hospital and long-term outcomes of immediate and staged PCI strategies for ARCA as culprit lesions during acute coronary syndrome (ACS)., Methods: Among 102.376 PCIs performed in 18 European centers, a total of 85 patients presenting with acute coronary syndrome undergoing ARCA PCI were finally included in the analysis. PCI strategy (stenting performed during the immediate vs staged procedure) and pharmacological approach adopted were collected. The primary outcome was procedural success (technical success without in-hospital MACE)., Results: The primary outcome occurred in 48.2 % of cases, with no significant differences observed between the immediate and staged PCI groups (50.9 % vs 43.3 %, p = 0.504). Patients in the staged-PCI group had a significantly higher rate of intravenous anticoagulant use (83.3 % vs 48.1 %, p = 0.002), BARC type 3 and 5 bleedings (12.9 % vs 1.9 %, p = 0.037), and longer in-hospital stay (7.40 ± 5.11 vs 9.5 ± 5.25 days, p = 0.049). After multivariate analysis, no independent predictors for procedural success were found in either group. Target lesion failure occurred in 24.1 % of cases without differences between groups at a median follow-up of three years., Conclusions: Among patients undergoing ARCA PCI in the setting of ACS, immediate or staged PCI were associated with similar in-hospital and long-term outcomes. However, staged PCI was associated with a higher risk of major bleeding events and longer length of stay compared to immediate PCI strategy., Competing Interests: Declaration of competing interest Dr. Azzalini received consulting fees from Abiomed, Teleflex, GE Healthcare, Philips, Abbott Vascular, Asahi Intecc, and Cardiovascular Systems, Inc.; Corrado Tamburino is a consultant for Medtronic and received speaker honoraria from Meril. Ferdinando Varbella receives consulting fees from Amgen, Sanofi, Pfizer, Astra Zeneca, Daichi Sankyo and Bayer; Alessio La Manna is a proctor for Kardia srl, Terumo Italia and GADA spa. Jose Maria De La Torre Hernandez received consulting fees from Boston Scientific, Medtronic, Abbot, Biotronik and Daichii Sankyo. Massimo Leoncini speaker honoraria from Boston Scientific, Terumo, Shockwave Medical, Penumbra and Daichii Sankyo. The other coauthors do not have any conflict of interest related to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This technical note aims to provide a detailed description of our arthroscopic technique for suture fixation of posterior cruciate ligament (PCL) tibial avulsion fractures. Various surgical approaches have been described, including both open and arthroscopic techniques. The arthroscopic approach can be less disruptive and more accurate in visualizing anatomic landmarks. It also may ensure good and reliable fracture reduction and fixation. This article describes a technique for arthroscopic all-inside fixation of PCL avulsion fractures using a double-tunnel pullout method. The procedure involves trans-septal visualization and whipstitching suturing of the PCL with 1.5-mm high-strength, nonresorbable transverse ribbon suture (LabralTape; Arthrex, Naples, FL) and a crosstie-like suture with a high-strength, nonresorbable suture tape (FiberTape; Arthrex) embracing the PCL from anterior to posterior. Finally, the avulsion fracture is secured by tensioning a high-strength suture tape from the femur to the tibia along the PCL structure as an InternalBrace ligament augmentation (Arthrex). This technique allows for anatomic reduction and stable fixation of the displaced fracture through optimal trans-septal visualization and the PCL whipstitching technique, further secured by the InternalBrace ligament augmentation, enabling early and intensive rehabilitation., Competing Interests: All authors (M.C., D.D., L.D., L.B., D.V., F.G., A.M.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Aims: Intracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features., Methods: A systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis., Results: The meta-analysis encompassed 31'385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference -0.88, 95% CI -1.13 to -0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference -0.02, 95% CI -0.03 to -0.01) and fibrous plaque areas (mean difference -0.03, 95% CI -0.03 to -0.03)., Conclusion: This meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making., Competing Interests: Declaration of competing interest A. C. has consultancy agreements with Medyria and Nanoflex. B. S. received research grants to the institution from the OPO Foundation, the Iten-Kohaut Foundation, the German Center for Cardiovascular Research (DZHK), Boston Scientific, and Edwards Lifesciences and has received consulting and speaker fees from Boston Scientific and Abbott Vascular. B.S. has been supported by the H.H. Sheikh Khalifa bin Hamad Al-Thani Research Programme. The remaining authors have nothing to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aim: The ideal surgical intervention for secondary mitral regurgitation (SMR), a disease of the left ventricle not the mitral valve itself, is still debated. We performed an updated systematic review and study-level meta-analysis investigating mitral valve repair (MVr) versus mitral valve replacement (MVR) for adult patients with SMR, with or without coronary artery disease (CAD)., Methods: PubMed, CENTRAL and EMBASE were searched for studies comparing MVr versus MVR. Randomized trial or observational studies were considered eligible. Primary endpoint was long-term mortality for any cause. Kaplan-Meier survival curves were reconstructed and compared with Cox linear regression. Landmark analysis and time-varying hazard ratio (HR) were analyzed. Sensitivity analyses included meta-regression and separate sub-analysis. A random effects model was used., Results: Twenty-three studies (MVr=3,727 and MVR=2,839) were included. One study was a randomized trial, and 19 studies were adjusted. The mean weighted follow-up was 3.7±2.8 years. MVR was associated with significative greater late mortality (HR=1.26; 95 % CI, 1.14-1.39; P<0.0001) at 10-year follow-up. There was a time-varying trend showing an increased risk of mortality in the first 2 years after MVR (HR=1.38; 95 % CI, 1.21-1.56; P<0.0001), after which this difference dissipated (HR=0.94; 95 % CI, 0.81-1.09; P=0.41). Separate sub-analyses showed comparable long-term mortality in patients with concomitant coronary surgery ≥90 %, left ventricle ejection fraction ≤40 %, and sub-valvular apparatus preservation rate of 100 %., Conclusions: Compared to repair, MVR is associated with higher probability of mortality in the first 2 years following surgery, after which the two procedures showed comparable late mortality rate., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Inflammatory rheumatic diseases are different pathologic conditions associated with a deregulated immune response, codified along a spectrum of disorders, with autoinflammatory and autoimmune diseases as two-end phenotypes of this continuum. Despite pathogenic differences, inflammatory rheumatic diseases are commonly managed with a limited number of immunosuppressive drugs, sometimes with partial evidence or transferring physicians' knowledge in different patients. In addition, several randomized clinical trials, enrolling these patients, did not meet the primary pre-established outcomes and these findings could be linked to the underlying molecular diversities along the spectrum of inflammatory rheumatic disorders. In fact, the resulting patient heterogeneity may be driven by differences in underlying molecular pathology also resulting in variable responses to immunosuppressive drugs. Thus, the identification of different clinical subsets may possibly overcome the major obstacles that limit the development more effective therapeutic strategies for these patients with inflammatory rheumatic diseases. This clinical heterogeneity could require a diverse therapeutic management to improve patient outcomes and increase the frequency of clinical remission. Therefore, the importance of better patient stratification and characterization is increasingly pointed out according to the precision medicine principles, also suggesting a new approach for disease treatment. In fact, based on a better proposed patient profiling, clinicians could more appropriately balance the therapeutic management. On these bases, we synthetized and discussed the available literature about the patient profiling in regard to therapy in the context of inflammatory rheumatic diseases, mainly focusing on randomized clinical trials. We provided an overview of the importance of a better stratification and characterization of the clinical heterogeneity of patients with inflammatory rheumatic diseases identifying this point as crucial in improving the management of these patients., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest for this work., (Copyright © 2024. Published by Elsevier B.V.)

Background: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication., Objectives: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry., Methods: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes., Results: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients., Conclusions: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful., Condensed Abstract: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high., Competing Interests: Declaration of competing interest A. Aminian is a consultant and proctor for Boston Scientific and Abbott. I. Akin received lecture and proctoring fees from Boston Scientific for the Watchman Okkluder. J. Lund discloses a clinical advisor (proctor) role in LAAC (Abbott) and lecture fees (Abbott, Boston scientific). E. Guerios serves as proctor for LAA closure for Abbott and Lifetech Scientific. N. Amabile has received proctoring and consulting fees from Abbott Vascular and Boston Scientific. C. Skurk has received proctor honoraria from Boston Scientific and speaker fees from Boston Scientific and Lifetech Scientific. J. Harvey is proctor for Abiomed, Boston Scientific and Medtronic and part of the Speaker's bureau for Abiomed, Boston Scientific and Medtronic. He also is part of the advisory board for Avail, Boston Scientific and Medtronic. H. Sievert has received study honoraria to institution, travel expenses and consulting fees from 4tech Cardio, Abbott, Ablative Solutions, Adona Medical, Akura Medical, Ancora Heart, Append Medical, Axon, Bavaria Medizin Technologie GmbH, Bioventrix, Boston Scientific, Cardiac Dimensions, Cardiac Success, Cardimed, Cardionovum, Celonova, Contego, Coramaze, Croivalve, CSL Behring LLC, CVRx, Dinova, Edwards, Endobar, Endologix, Endomatic, Esperion Therapeutics, Inc., Hangzhou Nuomao Medtech, Holistick Medical, Intershunt, Intervene, K2, Laminar, Lifetech, Magenta, Maquet Getinge Group, Metavention, Mitralix, Mokita, Neurotronic, NXT Biomedical, Occlutech, Recor, Renal Guard, Shifamed, Terumo, Trisol, Vascular Dynamics, Vectorious Medtech, Venus, Venock, Vivasure Medical, Vvital Biomed and Whiteswell. M. Kühne received personal fees from Bayer, Böhringer Ingelheim, Pfizer BMS, Daiichi Sankyo, Medtronic, Biotronik, Boston Scientific, Johnson & Johnson, and F. Hoffmann-La Roche Ltd., as well as grants from Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo. S. Sabir is part of the Boston Scientific WATCHMAN advisory board. J. Kim has received proctoring fees from Abbott Vascular. M. Montorfano received consultant fees from Abbott, Boston Scientific, Kardia. M. Ancona received consultant fees from Abbott. Relevant research funding went to Vanderbilt University Medical Center from Boston Scientific, Boehringer-Ingelheim, Medtronic and Atricure, where C. Ellis is practicing. He also reseves a consultant and advisor fee from Abbott Medical, Atricure, Boston Scientific, Medtronic. L. Nombela-Franco is proctor for Abbott Vascular and has received lectures fees from Boston Scientific. A. Natale has received speaker honoraria from Boston Scientific, Biosense Webster, St. Jude Medical, Biotronik, and Medtronic. He also is a consultant for Biosense Webster, St. Jude Medical, and Janssen. All other authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Maternal cardiovascular adaptation during pregnancy is essential for fetal development. Structural and functional changes, including increased blood volume, heart rate, and myocardial hypertrophy, are crucial for optimal tissue perfusion. Recent evidence supports viewing maternal and fetal cardiovascular systems as a unified functional unit, emphasizing the significance of hemodynamic evaluation in pregnancy. Some obstetrical syndromes result from maladaptive maternal cardiovascular responses. Non-invasive hemodynamic tests, like transthoracic echocardiography, aid in distinguishing phenotypes, guiding tailored management strategies for hypertensive disorders. Establishing obstetric hemodynamics as a multidisciplinary field, termed "Obstetric Echodynamics," promises improved clinical care through standardized practices, interdisciplinary cooperation, and enhanced education., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension., Methods: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated., Results: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal., Conclusions: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The potential benefit on long term outcomes of Percutaneous Coronary Intervention (PCI) on Unprotected Left Main (ULM) driven by IntraVascular UltraSound (IVUS) remains to be defined., Methods: IMPACTUS LM-PCI is an observational, multicenter study that enrolled consecutive patients with ULM disease undergoing coronary angioplasty in 13 European high-volume centers from January 2002 to December 2015. Major Adverse Cardiovascular Events (MACEs) a composite of cardiovascular (CV) death, target vessel revascularization (TVR) and myocardial infarction (MI) were the primary endpoints, while its single components along with all cause death the secondary ones., Results: 627 patients with ULM disease were enrolled, 213 patients (34%) underwent IVUS-guided PCI while 414 (66%) angioguided PCI. Patients in the two cohorts had similar prevalence of risk factors except for active smoking and clinical presentation. During a median follow-up of 7.5 years, 47 (22%) patients in the IVUS group and 211 (51%) in the angio-guided group underwent the primary endpoint (HR 0.42; 95% CI [0.31-0.58] p < 0.001). After multivariate adjustment, IVUS was significantly associated with a reduced incidence of the primary endpoint (adj HR 0.39; 95% CI [0.23-0.64], p < 0.001), mainly driven by a reduction of TVR (ad HR 0.30, 95% CI [0.15-0.62], p = 0.001) and of all-cause death (adj HR 0.47, 95% CI [0.28-0.82], p = 0.008). IVUS use, age, diabetes, side branch stenosis, DES and creatinine at admission were independent predictors of MACE., Conclusions: In patients undergoing ULM PCI, the use of IVUS was associated with a reduced risk at long-term follow-up of MACE, all-cause death and subsequent revascularization., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Renal fibrosis is now recognized as a main determinant of renal pathology to include chronic kidney disease. Deposition of pathological matrix in the walls of glomerular capillaries, the interstitial space, and around arterioles predicts and contributes to the functional demise of the nephron and its surrounding vasculature. The recent identification of the major cell populations of fibroblast precursors in the kidney interstitium such as pericytes and tissue-resident mesenchymal stem cells, or bone-marrow-derived macrophages, and in the glomerulus such as podocytes, parietal epithelial and mesangial cells, has enabled the study of the fibrogenic process thought the lens of involved immunological pathways. Besides, a growing body of evidence is supporting the role of the lymphatic system in modulating the immunological response potentially leading to inflammation and ultimately renal damage. These notions have moved our understanding of renal fibrosis to be recognized as a clinical entity and new main player in autoimmunity, impacting directly the management of patients., 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 © 2023. Published by Elsevier B.V.)

Background: Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal., Methods: TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS)., Results: From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) (P = .001), opioid use (P = .004), bone metastases number (P < .001), baseline PSA (P = .006), Hb (P < .001), ALP (P < .001) and LDH (P = .002), time between ADT and docetaxel start (P = .018), 3-month PSA (P < .001) and ALP (P < .001), and number of docetaxel cycles (P < .001). OS-related variables were PSA at diagnosis (P = .024), primary tumor treatment (P = .022), baseline pain (P = .015), opioid use (P < .001), bone metastases number (P < . 001), baseline Hb (P < .001), ALP (P < .001) and LDH (P = .001), NLR ratio (P = .039), 3-month PSA (P < .001) and ALP (P < .001) and docetaxel cycles number (P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS., Conclusion: Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy., Competing Interests: Disclosure All authors have no conflict of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The optimal revascularization strategy in patients with heart failure with reduced ejection fraction (HFrEF) remains to be elucidated. The aim of this paper is to compare the mid-term mortality rate among patients with severely reduced ejection fraction (EF) and complex coronary artery disease who underwent coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) with Impella support, or without., Methods: Randomized control trials and propensity-adjusted observational studies including patients with ischemic cardiomyopathy (ICM) and severe EF reduction undergoing revascularization were selected. Different revascularization strategies (CABG, supported PCI, and PCI without Impella) were compared in pairwise and network meta-analysis. The primary endpoint was mid-term mortality (within the first year after revascularization)., Results: Fifteen studies, mostly observational (17,841 patients; 6779 patients treated with CABG, 8478 treated with PCI without Impella, and 2584 treated with Impella-supported PCI) were included in this analysis. The median age was 67.8 years (IQR 65-70.1), 21.2% (IQR 16.4-26%) of patients were female sex, and a high prevalence of cardiovascular risk factors was noted across the entire population. At pairwise analysis, CABG and PCI without Impella showed similar one-year all-cause mortality (10.6% [IQR 7.5-12.6%] vs 12% [IQR 8.4-11.5%]) RR 0.85 CI 0.67-1.09, while supported PCI reduced one-year all-cause mortality compared to PCI without Impella (9.4% [IQR 5.7-12.5%] vs 10.6% [IQR 8.9-10.7%]) RR 0.77 CI 0.6-0.89. At network meta-analysis, supported PCI showed better results (RR 0.75, 95% CI 0.59-0.94) compared to CABG., Conclusion: Our analysis found that supported PCI may have a benefit over standard PCI in patients in direct comparison, and over CABG from indirect comparison, and with HFrEF undergoing revascularization. Further RCTs are needed to confirm this result. (PROSPERO CRD42023425667)., Competing Interests: Conflicts of interest Dr. Brilakis: consulting/speaker honoraria from Abbott Vascular, American Heart Association (associate editor Circulation), Amgen, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (Board of Directors), CSI, Elsevier, GE Healthcare, IMDS, Medtronic, Teleflex, and Terumo; research support: Boston Scientific, GE Healthcare; owner, Hippocrates LLC; shareholder: MHI Ventures, Cleerly Health, Stallion Medical., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: To assess the reproducibility of coronary tissue characterization by an Artificial Intelligence Optical Coherence Tomography software (OctPlus, Shanghai Pulse Medical Imaging Technology Inc.)., Methods: 74 patients presenting with multivessel ST-segment elevation myocardial infarction (STEMI) underwent optical coherence tomography (OCT) of the infarct-related artery at the end of primary percutaneous coronary intervention (PPCI) and during staged PCI (SPCI) within 7 days thereafter in the MATRIX (Minimizing Adverse Hemorrhagic Events by Transradial Access Site and angioX) Treatment-Duration study (ClinicalTrials.gov, NCT01433627). OCT films were run through the OctPlus software. The same region of interest between either side of the stent and the first branch was identified on OCT films for each patient at PPCI and SPCI, thus generating 94 pairs of segments. 42 pairs of segments were re-analyzed for intra-software difference. Five plaque characteristics including cholesterol crystal, fibrous tissue, calcium, lipid, and macrophage content were analyzed for various parameters (span angle, thickness, and area)., Results: There was no statistically significant inter-catheter (between PPCI and SPCI) or intra-software difference in the mean values of all the parameters. Inter-catheter correlation for area was best seen for calcification [intraclass correlation coefficient (ICC) 0.86], followed by fibrous tissue (ICC 0.87), lipid (ICC 0.62), and macrophage (ICC 0.43). Some of the inter-catheter relative differences for area measurements were large: calcification 9.75 %; cholesterol crystal 74.10 %; fibrous tissue 5.90 %; lipid 4.66 %; and macrophage 1.23 %. By the intra-software measurements, there was an excellent correlation (ICC > 0.9) for all tissue types. The relative differences for area measurements were: calcification 0.64 %; cholesterol crystal 5.34 %; fibrous tissue 0.19 %; lipid 1.07 %; and macrophage 0.60 %. Features of vulnerable plaque, minimum fibrous cap thickness and lipid area showed acceptable reproducibility., Conclusion: The present study demonstrates an overall good reproducibility of tissue characterization by the Artificial Intelligence Optical Coherence Tomography software. In future longitudinal studies, investigators may use discretion in selecting the imaging endpoints and sample size, accounting for the observed relative differences in this study., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The benefits of single (SITA) and bilateral internal thoracic arteries (BITA) in diabetics undergoing coronary bypass grafting (CABG) are conflicting. We undertook a study-level meta-analysis to compare early and long-term outcomes of both CABG configurations. PubMed, CENTRAL, and EMBASE were searched for studies comparing BITA versus SITA for isolated CABG surgery in diabetics. Randomized trials or observational studies were considered eligible for the analysis. Kaplan-Meier curves of long-term survival were reconstructed and compared with Cox linear regression; incidence rate ratios (IRR) with 95% confidence intervals (CI) for long-term survival were calculated. Landmark analysis and time-varying hazard ratio (HR) were analyzed. Odds ratios (OR) were extracted for early mortality, postoperative stroke, deep sternal wound infection (DSWI), and myocardial infarction (MI). A random effects meta-analysis was performed. Sensitivity analyses included leave-one-out-analyses and meta-regression. Thirteen studies (7332 patients) were included. Overall, at 20-year follow-up, BITA was associated with higher survival (HR = 0.77; 95% CI, 0.71-0.84; P < 0.0001). Time-varying HR and landmark analysis reported BITA was associated with a higher rate of 10-year survival (HR = 0.75, 95% CI 0.68-0.82, P < 0.0001), while from 10 to 20-year follow-up no difference was revealed (HR = 0.99, 95% CI 0.82-1.19, P = 0.93). There was no increase in early mortality, postoperative MI, stroke, or DSWI between the groups. At meta-regression, the higher the age, the higher the long-term overall survival in patients with BITA. In diabetics, the BITA approach is associated with improved 10-year survival with no increase in early mortality, MI, stroke, or DSWI. In the 10-20-year timeframe, BITA and SITA showed comparable survival., 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 © 2023 Elsevier Inc. All rights reserved.)

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) encompasses a group of rare, multisystem autoimmune disorders characterised by the occurrence of inflammation and damage to small blood vessels, leading to a wide range of clinical manifestations. They include granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Outcomes for patients with MPA and GPA have been transformed over recent years. However, the establishment of effective maintenance therapy aiming to balance the risks of disease relapse with those related to prolonged immunosuppression has become a clinical priority. This review aims to explore two differing perspectives on this unsolved problem. Pros and Cons of the following approaches will be discussed: "Biomarker-guided personalised approach on top of generic maintenance strategy guidelines" or "ANCA specificity-related personalised maintenance treatment after intensive B-cell depletion"?, Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dario Roccatello reports a relationship with Novartis Pharma AG that includes: consulting or advisory. Dario Roccatello reports a relationship with Vifor Pharma Ltd. that includes: consulting or advisory. Dario Roccatello reports a relationship with GlaxoSmithKline Inc. that includes: speaking and lecture fees. Dario Roccatello reports a relationship with Bristol Myers Squibb Co that includes: speaking and lecture fees. Dario Roccatello reports a relationship with Roche that includes: speaking and lecture fees. Dario Roccatello reports a relationship with Novartis Pharma SAS that includes: speaking and lecture fees. Dario Roccatello reports a relationship with UptoDate Inc. that includes: paid expert testimony. Mark A Little reports a relationship with AnaptysBio Inc. that includes: consulting or advisory. Mark A Little reports a relationship with Lightstone that includes: consulting or advisory. Mark A Little reports a relationship with Vifor Pharma Ltd. that includes: funding grants. Mark A Little reports a relationship with Euroimmun Medical Laboratory Diagnostics AG Institute for Experimental Immunology that includes: funding grants., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Complement levels have been proposed as candidate biomarkers of disease activity and obstetric risk in systemic lupus erythematosus (SLE) pregnancies, but their reliability has been questioned due to the physiologic fluctuations of complement during gestation. Thus, this network meta-analysis aimed at assessing the clinical significance of complement fluctuations in lupus pregnant women., Methods: Corresponding authors of 19 studies meeting inclusion criteria were invited to contribute with additional data including C3 and C4 levels [before pregnancy, at conception, in every trimester (T) and 3 months after delivery]; data were pooled together in a network meta-analysis., Results: A total of 532 lupus women from four studies were included in the analysis. In SLE women, C3 and C4 increased progressively during gestation: levels remained stable during T1 and peaked in T2 to decrease in T3. Patients with previous lupus nephritis (LN) and those who experienced flares during pregnancy had significantly lower mean levels of C3 and C4 at all timepoints. The lowest levels of complement were observed, particularly during T1, in patients with LN and gestational flare. Both reduction and the lack of increase of C3 and C4 levels at T1 versus conception were associated with gestational flares, particularly in LN patients. Pregnancies with flare had a statistically significant higher rate of maternal and fetal complications(60% versus 50.3%; p = 0.03)., Conclusions: Low complement levels, particularly in T1, were associated with a higher frequency of gestational flare. Either reduction or smaller increase of C3 and/or C4 levels, even within normal range, might predict flares especially in early gestation., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The clinical value of high-risk coronary plaque characteristics (CPCs) to inform intensified medical therapy or revascularization of non-flow-limiting lesions remains uncertain., Objectives: The authors performed a systematic review and meta-analysis to study the prognostic impact of CPCs on patient-level and lesion-level major cardiovascular adverse events (MACE)., Methods: Thirty studies (21 retrospective, 9 prospective) with 30,369 patients evaluating the association of CPCs with MACE were included. CPCs included high plaque burden, low minimal lumen area, thin cap fibroatheroma, high lipid core burden index, low-attenuation plaque, spotty calcification, napkin ring sign, and positive remodeling., Results: CPCs were evaluated with the use of intracoronary modalities in 9 studies (optical coherence tomography in 4 studies, intravascular ultrasound imaging in 3 studies, and near-infrared spectroscopy intravascular ultrasound imaging in 2 studies) and by means of coronary computed tomographic angiography in 21 studies. CPCs significantly predicted patient-level and lesion-level MACE in both unadjusted and adjusted analyses. For most CPCs, accuracy for MACE was modest to good at the patient level and moderate to good at the lesion level. Plaques with more than 1 CPC had the highest accuracy for lesion-level MACE (AUC: 0.87). Because the prevalence of CPCs among plaques was low, estimated positive predictive values for lesion-level MACE were modest. Results were mostly consistent across imaging modalities and clinical presentations, and in studies with prevailing hard outcomes., Conclusions: Characterization of CPCs identifies high-risk atherosclerotic plaques that place lesions and patients at risk for future MACE, albeit with modest sensitivity and positive predictive value (Coronary Plaque Characteristics Associated With Major Adverse Cardiovascular Events Among Atherosclerotic Patients and Lesions; CRD42021251810)., Competing Interests: Funding Support and Author Disclosures In the past 2 years, Dr Porto has received speaker or advisor fees from GE, Terumo, Medtronic, Abbott, Philips, Sanofi, Amgen, and Daiichi-Sankyo, all outside of the scope of the submitted work; his laboratory has received support from Chiesi and Amgen. Dr Williams is supported by the British Heart Foundation (FS/ICRF/20/26002) and has given lectures for Canon Medical Systems and Siemens Healthineers. Dr Pontone has received speaker honoraria or research grants from GE Healthcare, Heartflow, Bracco, and Boehringer. Dr Libby is an unpaid consultant to or involved in clinical trials for Amgen, AstraZeneca, Baim Institute, Beren Therapeutics, Cartesian, Esperion, Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Medimmune, Merck, Novo Nordisk, Merck, Novartis, Pfizer, and Sanofi-Regeneron. Dr Libby is a member of scientific advisory boards for Amgen, Corvidia Therapeutics, Caristo, CSL Behring, DalCor Pharmaceuticals, Dewpoint, PlaqueTec, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Medimmune, Novartis, TenSixteen Bio, and XBiotech; his laboratory has received research funding in the last 2 years from Novartis; he is on the Board of Directors of and has a financial interest in Xbiotech, a company developing therapeutic human antibodies; his interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies; and he has received funding support from the National Heart, Lung, and Blood Institute (1R01HL134892), the American Heart Association (18CSA34080399), the RRM Charitable Fund, and the Simard Fund. Dr Stone has received speaker honoraria from Pulnovo and Infraredx; is a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity/options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; his daughter is an employee of Medtronic; and his employer, Mount Sinai Hospital, receives research support from Abbott, Bioventrix, Cardiovascular Systems, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, and V-wave. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms. At least 14 target antigens have been identified, accounting for 80%-90% of cases of MN. Many of the forms of MN associated with these novel MN target antigens have distinctive clinical and pathologic phenotypes. The Mayo Clinic consensus report on MN proposes a 2-step classification of MN. The first step, when possible, is identification of the target antigen, based on a multistep algorithm and using a combination of serology, staining of the kidney biopsy tissue by immunofluorescence or immunohistochemistry, and/or mass spectrometry methodology. The second step is the search for a potential underlying disease or associated condition, which is particularly relevant when knowledge of the target antigen is available to direct it. The meeting acknowledges that the resources and equipment required to perform the proposed testing may not be generally available. However, the meeting consensus was that the time has come to adopt an antigen-based classification of MN because this approach will allow for accurate and specific MN diagnosis, with significant implications for patient management and targeted treatment., (Copyright © 2023 International Society of Nephrology and Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Pulmonary embolism (PE) represents one of the leading causes of death worldwide and mainly treated with medical management, although the utility of more invasive approaches has emerged more recently. This meta-analysis aims to evaluate the 30-day mortality of intermediate-to-high risk PE across different treatment strategies., Methods: A systematic literature review and meta-analysis was conducted using PubMed and Cochrane databases. All studies reporting 30-day mortality rates in intermediate-to-high-risk PE were included. Meta-regression analysis and sensitivity analysis were performed on the primary endpoint, 30-day mortality, and secondary endpoints (RV/LV ratio, mPAP, and long-term mortality, any bleeding events)., Results: Of the 2390 studies published between 2000 and 2022, 76 studies (74 observational and 2 RCTs for a total of 1,194,285 patients in the medical cohort and 3007 in the interventional cohort) were included. The median age was 71.4 (IQR 62.8-77.3) years, 53.6% were women. 30-day mortality in the patients treated with medical management was 9.1% (6.6-12.6). In the interventional cohort, 30-day mortality was 2.1% (1.5-3.1) while the pre- vs post-procedure change in mean difference was -6.1 mmHg (-11.2 to -1.1) for mPAP and - 0.41 (-0.51 to - 0.31) for RV/LV ratio. The overall bleeding rate in the interventional cohort was 4.9% (CI 2.6-8.9), without differences between the two strategies (RR 1.26 CI 0.89-1.78)., Conclusion: Intermediate-high-risk mortality in pulmonary embolisms treated with medical management remains high in the modern era. Despite the absence of comparative studies, an interventional approach may have a lower 30-day mortality rate and a good safety profile., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Guiding catheter extensions (GCEs) have become indispensable tools in the modern approach to percutaneous coronary intervention (PCI). The support offered during complex PCI of uncrossable, or tortuous lesions is particularly valuable in the setting of chronic total occlusions (CTO), both for conventional anterograde wire escalation and for anterograde or retrograde dissection and re-entry techniques. This EuroCTO consensus document describes the use of GCE during CTO recanalization and provides a practical guide to anatomies and techniques in which these devices are applicable. We describe the peculiar features of the most-used device and the practical technique for GCE delivery in standard PCI; further specific indications for antegrade and retrograde CTO PCI are discussed in a specific section. In the antegrade approach, the GCEs may be useful to increase support or facilitate antegrade dissection and re-entry techniques, while in the retrograde approach for reverse controlled antegrade and retrograde tracking, to increase retrograde support for gear delivery, for treatment of CTO in bifurcation and ipsilateral externalization with a single guide catheter. The last section of the paper describes GCE-related complications, challenges, limitations, and future perspectives., Competing Interests: Funding Support and Author Disclosures Dr Mashayekhi has received consulting/speaker/proctoring honoraria from Abbott Vascular, Abiomed, Ashai Intecc, AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi Sankyo, Medtronic, Shockwave Medical, Teleflex, and Terumo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The resorbable magnesium scaffold (RMS) is a second-generation bioresorbable scaffold (BRS) that has shown conflicting results in previous studies. These findings suggest that patient selection and implantation technique may have an impact on clinical outcomes. This study aimed to investigate the safety and long-term effectiveness of RMS in a narrowly selected population., Methods: SHERPA-MAGIC is an investigator-driven, multicenter, prospective, single-arm study that enrolled patients undergoing BRS coronary implantation in 18 Italian centers. The present analysis considered the first 543 enrolled patients treated with RMS, with a minimum follow-up of 1 year. The study protocol included strict criteria for patient selection and standardization of RMS implantation. The primary outcome was the occurrence of the vessel-oriented composite endpoints (VOCE), including cardiac death, target vessel myocardial infarction, and ischemia-driven target vessel revascularization., Results: Overall, 635 vessels were treated. The 1-year cumulative occurrence of VOCE was 22 (3.5%, 95% CI 2.2%-5.2%), which was significantly lower than the prespecified estimation (from 5.5% to 8.5%). At the median follow-up of 3.5 [2.6-4.3] years, there were 3 (0.5%) cardiac deaths, 12 (1.9%) target vessel myocardial infarctions, and 33 (5.2%) ischemia-driven target vessel revascularizations. A total of 37 (5.8%, 95%CI 4.1%-7.9%) VOCEs were detected. Scaffold thrombosis occurred in 4 (0.6%, 95%CI 0.1%-1.6%) cases. Patient-level analysis confirmed the findings of the vessel-level analysis., Conclusions: These results confirm the safety and performance of RMS technology. If confirmed in randomized controlled trials, they may rekindle interest in the use of scaffolds in daily practice., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interests. All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation., (Copyright © 2023 Elsevier B.V. All rights reserved.)

A syndemic is the co-existence of two or more health problems (including both social and biological features) that adversely influence each other with negative consequences on disease outcomes and perpetuation of inequalities. The syndemic approach can be applied to better understand the course of rheumatic musculoskeletal diseases (RMD) involving the study of adverse biological pathways and social determinants of health (SDH) all under the same framework. Identifying if a syndemic exists within RMDs may include investigating the synergic interactions between comorbidity (e.g., diabetes, obesity, chronic kidney diseases) and the concomitant of other adverse conditions (e.g., drug non-adherence, substance abuse), along with SDHs such as low household income, unemployment, low education, limited access to health care, as well as racial/ethnic discrimination. For decades, the understanding of RMDs progression has been based on causality, rather than investigating the kaleidoscopic web of connections that can potentially influence a disease course. The co-existence of health burdens in vulnerable populations, including those with RMD, specifically in certain socioeconomic groups, calls for new ways and strategies of thinking to improve our understanding of risk factors and co-morbidities to offer tailored interventions for clinical medicine and public health policy., 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 © 2023 Elsevier B.V. All rights reserved.)

Diagnosis of autoimmune diseases is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the conditions. This review focused on the current knowledge of the role of autoantibodies' testing in various diseases, such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, undifferentiated connective tissues disease, primary biliary cholangitis and primary sclerosing cholangitis. Similarly, the prognostic and diagnostic values of autoantibodies testing in patients with interstitial lung disease have been reviewed. In-depth research on the molecular action of these autoantibodies on immune regulation and diseases pathogenesis has been explored beyond their correlation with disease phenotypes, highlighting the impact of autoantibodies targeting on disease outcomes and etiopathogenesis., 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 © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of Competing Interest Michael Mahler and Chelsea Bentow are employees of Werfen (no stocks or stock options), a diagnostic company.

Aims: Patients with inflammatory bowel disease (IBD) are known to be at increased risk for venous thrombosis, while their risk for arterial ischemic events is debated. The purpose of this study was to conduct a systematic review of the published literature on the risk of myocardial infarction (MI) in IBD patients and to identify any potential risk factors., Methods: The present study was performed according to PRISMA, with a systematic search on PubMed, Cochrane, and Google Scholar. Risk of MI was the primary end point, while all causes of death and stroke were secondary endpoints. Both univariate and multivariate pooled analysis were performed., Results: An overall population of 515,455 controls and 77,140 persons with IBD (26,852, 34.8% Crohn's disease, CD and 50,288, 65.2% ulcerative colitis, UC) was included. Mean age was similar across controls and IBD. Persons with CD and UC had lower rates of hypertension (14.5% vs. 14.6% vs. 25%), diabetes (2.9% vs. 5.2% vs. 9.2%) and dyslipidaemia (3.3% vs. 6.5% vs. 16.1%) compared to controls. Smoking did not significantly differ (17% vs. 17.5% vs. 10.6%). Pooled results of multivariate adjustment showed that, after a 5 years-follow-up, both CD and UC were at increased risk of MI (respectively HR 1.36 [1.12-1.64] and HR 1.24 [1.05-1.46]), of death (HR 1.55 [1.27-1.90] and HR 1.29 [1.01-1.64]), and of other CV disease as stroke (HR 1.22 [1.01-1.49] and HR 1.09 [1.03-1.15], all 95% CI)., Conclusions: Persons with IBD are at increased risk of MI, despite a lower prevalence of the classic risk factors for MI (hypertension, diabetes, dyslipidemia)., Competing Interests: Declaration of Competing Interest Conflict of interest: none declared., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The etiological complexity of Behçet syndrome (BS), an immune-mediated rare form of vasculitis characterized by multi-organ involvement, is still elusive due to an incomplete understanding of the synergy between genetic susceptibility, environmental triggers, and an abnormal immune response. Long-standing theories regarding the origins of BS include the involvement of infectious organisms supporting an aberrant immunological response through different mechanisms, including molecular mimicry. Additionally, it has been demonstrated that the BS phenotypes are linked to oral and gut microbiome dysbiosis, which is a dynamic reservoir of millions of microbes containing proteins and metabolites that can mimic the autoantigens. Infections, including viral pathogens, could potentially trigger the inflammation and symptoms of BS. In this review, we aim to describe the available evidence on the cross-talk between BS and infections in order to discuss potential clinical implications and possible therapeutic targets., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Elevated resting heart rate is a risk factor for cardiovascular events., Objective: The purpose of this study was to investigate the clinical significance of nocturnal heart rate (nHR) and 24-hour mean heart rate (24h-HR) obtained by continuous remote monitoring (RM) of implantable devices., Methods: We analyzed daily-sampled trends of nHR, 24h-HR, and physical activity in patients on β-blocker therapy for chronic heart failure and with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (CRT-Ds). Patients were grouped by average nHR and 24h-HR quartile during follow-up to estimate the respective incidence of nonarrhythmic death and device-treated ventricular tachycardia/fibrillation (VT/VF)., Results: The study cohort included 1330 patients (median age 69 years [interquartile range 61-77 years]; 41% [n = 550] with CRT-D; median follow-up 25 months [interquartile range 13-42 months]). Compared with patients in the lowest nHR quartile (≤57 beats/min) group, patients in the highest quartile group (>65 beats/min) had an increased risk of nonarrhythmic death (adjusted hazard ratio [AHR] 2.25; 95% confidence interval [CI] 1.13-4.50; P = .021) and VT/VF (AHR 1.98; 95% CI 1.40-2.79; P < .001) and were characterized by the lowest level of physical activity (P ≤ .0004 vs every other nHR quartiles). The highest 24h-HR quartile group (>75 beats/min) showed an increased risk of VT/VF (AHR 2.13; 95% CI 1.52-2.99; P < .001) and a weaker though significant association with nonarrhythmic mortality (AHR 1.80; 95% CI 1.00-3.22; P = .05) as compared with the lowest 24h-HR quartile group (≤65 beats/min)., Conclusion: In remotely monitored patients with implantable cardioverter-defibrillator/CRT-D on β-blocker therapy for heart failure, elevated heart rates (nHR >65 beats/min and 24h-HR >75 beats/min) were associated with increased mortality and VT/VF risk. nHR showed a stronger association than 24h-HR with worst prognosis and lowest physical activity., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS)., Methods: We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months., Results: A total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles., Conclusion: Three different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN)., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Background: The occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ., Objectives: The aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS., Methods: In the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5 mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding., Results: Persistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95% CI: 1.48-3.64; P < 0.001; NACE: adjusted HR: 2.29; 95% CI: 1.48-3.52; P < 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95% CI: 2.03-5.82; P < 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria., Conclusions: Among patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627)., Competing Interests: Funding Support and Author Disclosures The trial was sponsored by Società Italiana di Cardiologia Invasiva (a nonprofit organization), which received grant support from The Medicines Company and Terumo. This substudy did not receive any direct or indirect funding. Prof Leonardi has received grants and personal fees from AstraZeneca; and has received personal fees from Daiichi Sankyo, Bayer, Pfizer/Bristol Myers Squibb, ICON, Chiesi, and Novo Nordisk (all outside the submitted work). Prof Vranckx has received personal fees from Bayer, Daiichi Sankyo, and CLS Behring (all outside the submitted work). Dr Tebaldi has received research grants from GADA and Abbott Vascular; and has received personal fees from Abbott (all outside the submitted work). Prof Andò has received personal fees and nonfinancial support from Daiichi Sankyo, Boeringer Ingelheim, and Amgen; and has received personal fees from AstraZeneca, Chiesi, and Biosensors (all outside the submitted work). Dr Brugaletta has received a research grant to the institution from AstraZeneca; has received personal fees from Abbott Vascular (outside the submitted work); and has served as an advisory board member for Boston Scientific, iVascular, and Teleflex. Dr Adamo has received speaker fees from Abbott Vascular and Medtronic (all outside the submitted work). Prof Windecker has received research and educational grants to the institution from Abbott, Amgen, AstraZeneca, Bristol Myers Squibb, Bayer, Biotronik, Boston Scientific, Cardinal Health, Cardiovalve, CSL Behring, Daiichi Sankyo, Edwards Lifesciences, Guerbet, Infraredx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi, Sinomed, Terumo, and V-Wave; has served as an unpaid advisory board member and/or unpaid member of the steering or executive groups of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Biotronik, Cardiovalve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, Terumo, V-Wave, and Xeltis (but has not received personal payments from pharmaceutical companies or device manufacturers); and is a member of the steering or executive committee groups of several investigator-initiated trials that receive funding from industry without impact on his personal remuneration. Prof Valgimigli has received grants and personal fees from Abbott, Terumo, and AstraZeneca; has received personal fees from Chiesi, Bayer, Daiichi Sankyo, Amgen, Alvimedica, Biosensors, and Idorsia; and has received grants from Medicure (outside the submitted work). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Background: Coronary chronic total occlusion lesions (CTOs) confer an increased risk of arrhythmic events among patients with ischemic cardiomyopathy (ICM) and implantable cardioverter-defibrillator (ICD) carriers, however the impact of CTO recanalization in this population remains unassessed., Aims: Evaluate the impact of CTOs percutaneous coronary interventions (PCI) on arrhythmic events., Methods: Patients with ICM and ICD from the VACTO I-II registries: patients with medically treated CTO (CTO-OMT group) and without CTO (no-CTO group) were compared after inverse-probability-weighting adjustment (IPWT) with a similar population of consecutive patients undergoing CTO-PCI. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality., Results: The total of 622 patients (mean age 67 ± 10 years, mean left ventricular ejection fraction 36 ± 11%) included in the analysis was composed by: CTO-PCI patients n = 113, CTO-OMT patients n = 286, no-CTO patients n = 223. In the CTO-PCI group, compared to the CTO-OMT group, 5-year Kaplan Meier estimates for appropriate ICD therapy (20.4% vs. 56.4%, IPW-adjusted HR: 0.45, 95% CI 0.29-0.71) and mortality (8.8% vs. 23%, IPW-adjusted HR: 0.43, 95% CI 0.22-0.85) were lower, driven by infarct related artery CTO (IRA-CTO) PCI, while similar to those occurring in the no-CTO group., Conclusions: In this large population, those with CTO receiving PCI had lower arrhythmic event rates and lower mortality compared to the CTO-OMT group, while showing an event rate similar to no-CTO patients. Sensitivity analyses suggest that the beneficial effect on the arrhythmic outcome was driven by IRA-CTO revascularization., Classification: Chronic total occlusion., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: We aimed to apply and compare the QRISK3 and the adjusted Global AntiPhospholipid Syndrome (APS) Score (aGAPSS) in a cohort of systemic lupus erythematosus (SLE) patients, with and without a concomitant diagnosis of APS, in order to assess their augmented risk of developing cardiovascular diseases (CVDs)., Methods: Patients (25-85 yo) with a diagnosis of SLE and/or of Secondary APS (SAPS) were included. QRISK3 was calculated using the official online calculator; aGAPSS using the validated point-values based on aPL-profile and independent risk factors., Results: The cohort included 142 SLE patients: 34 SAPS (23.9%) and 108 SLE patients without APS (76.1%).When considering all the cohort, patients with cerebrovascular/coronary events showed higher values of aGAPSS (10.1 ± 6.2 vs. 5.8 ± 6.1; p = 0.007), but not of the QRISK3. Furthermore, a significant association was observed between the occurrence of these events and high-risk aGAPSS: p = 0.03 for aGAPSS≥8, p = 0.01 for aGAPSS ≥9, p = 0.008 for aGAPSS ≥10. aGAPSS strongly correlated with the occurrence of any thrombotic event, both at the uni- and multivariate analysis (p = 0.012 and p = 0.009). Male gender also resulted to positively correlate with the occurrence of any thrombotic event at both uni- and multivariate analysis (p = 0.017 and p = 0.03). Focusing on aPL-profile, regardless the diagnosis, we found a statistical significance only for aGAPSS (aPL+ =9.6 ± 6.3 vs. aPL- = 4.1 ± 5.1; p < 0.001)., Conclusions: Despite QRISK3 being more accurate than traditional risk score in predicting CVD risk in SLE patients, aGAPSS appears to be the most valuable tool for this purpose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The timing of hemodynamic support in acute myocardial infarction complicated by cardiogenic shock (AMICS) has yet to be defined. The aim of this meta-analysis was to evaluate the impact of timing of Impella initiation on early and midterm mortality., Methods: A systematic literature review and meta-analysis was conducted using PubMed and Cochrane databases. All studies reporting short-term mortality rates and timing of Impella placement in AMICS were included. Meta-regression analysis and sensitivity analysis were performed on the primary endpoint, short-term mortality (≤30 days), and secondary endpoints (midterm mortality, device-related bleeding, and limb ischemia)., Results: Of 1289 studies identified, 13 studies (6810 patients; 2970 patients identified as receiving Impella pre-PCI and 3840 patients receiving Impella during/post-PCI) were included in this analysis. Median age was 63.8 years (IQR 63-65.7); 76% of patients were male, and a high prevalence of cardiovascular risk factors was noted across the entire population. Short-term mortality was significantly reduced in those receiving pre-PCI vs. during/post-PCI Impella support (37.2% vs 53.6%, RR 0.7; CI 0.56-0.88). Midterm mortality was also lower in the pre-PCI Impella group (47.9% vs 73%, RR 0.81; CI 0.68-0.97). The rate of device-related bleeding (RR 1.05; CI 0.47-2.33) and limb ischemia (RR 1.6; CI 0.63-2.15) were similar between the two groups., Conclusion: This analysis suggests that Impella placement prior to PCI in AMICS may have a positive impact on short- and midterm mortality compared with post-PCI, with similar safety outcomes. Due to the observational nature of the included studies, further studies are needed to confirm this hypothesis (CRD42022300372)., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The impact of Impella and ECMO (ECPELLA) in cardiogenic shock (CS) remains to be defined. The aim of this meta-analysis is to evaluate the benefit of ECPELLA compared to VA-ECMO in patients with non post-pericardiotomy CS., Methods: All studies reporting short term outcomes of ECpella or VA ECMO in non post-pericardiotomy CS were included. The primary endpoint was 30-day mortality. Vascular and bleeding complications and LVAD implantation/heart transplant within 30-days were assessed as secondary outcomes., Results: Of 407 studies identified, 13 observational studies (13,682 patients, 13,270 with ECMO and 412 with ECpella) were included in this analysis. 30-day mortality was 55.8% (51.6-59.9) in the VA-ECMO group and 58.3% (53.5-63.0) in the ECpella group. At meta-regression analysis the implantation of IABP did not affect mortality in the ECMO group. The rate of major bleeding in patients on VA-ECMO and ECpella support were 21.3% (16.9-26.5) and 33.1% (25.9-41.2) respectively, while the rates of the composite outcome of LVAD implantation and heart transplantation within 30-days in patients on VA-ECMO and ECpella support were 14.4% (9.0-22.2) and 10.8%. When directly compared in 3 studies, ECpella showed a positive effect on 30-day mortality compared to ECMO (OR: 1.81: 1.039-3.159)., Conclusion: Our data suggest that ECpella may reduce 30-day mortality and increase left ventricle recovery, despite increased of bleeding rates., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Surgical indications for cerebral cavernous malformations (CCMs) remain significantly center- and surgeon-dependent; available grading systems are potentially limited, as they do not include epileptologic and radiologic data. Several experienced authors proposed a new grading system for CCM and the first group of patients capable of providing its statistical validation was analyzed., Methods: A retrospective series of 289 CCMs diagnosed between 2008 and 2021 was collected in a shared anonymous database among 9 centers. The new grading system ranges from -1 to 10. For each patient with cortical and cerebellar cavernous malformations the grading system was applied, and a retrospective outcome analysis was performed. We proposed a score of 4 as a cutoff for surgical indication., Results: Operated patients with a score ≥4 were grouped with non-operated patients with a score <4, as they constituted the group that received correct treatment according to the new grading system. Patients with a score ≥4, who underwent surgery and had an improved outcome, were compared to patients with a score ≥4 who were not operated (P = 0.04), and to patients with a score <4 who underwent surgery (P < 0.001)., Conclusions: This preliminary statistical analysis demonstrated that this new grading would be applicable in surgical reality. The cutoff score of 4 correctly separated the patients who could benefit from surgical intervention from those who would not. The outcome analysis showed that the treated patients in whom the grading system has been correctly applied have a better outcome than those in whom the grading system has not been applied., (Copyright © 2022 Elsevier Inc. All rights reserved.)