Impact of COVID-19 pandemic and infection on in hospital survival for patients presenting with acute coronary syndromes: A multicenter registry

Introduction: The impact of Covid-19 on the survival of patients presenting with acute coronary syndrome (ACS) remains to be defined. Methods: Consecutive patients presenting with ACS at 18 Centers in Northern-Italy during the Covid-19 outbreak were included. In-hospital all-cause death was the primary outcome. In-hospital cardiovascular death along with mechanical and electrical complications were the secondary ones. A case period (February 20, 2020-May 3, 2020) was compared vs. same-year (January 1\u2013February 19, 2020) and previous-year control periods (February 20\u2013May 3, 2019). ACS patients with Covid-19 were further compared with those without. Results: Among 779 ACS patients admitted during the case period, 67 (8.6%) tested positive for Covid-19. In-hospital all-cause mortality was significantly higher during the case period compared to the control periods (6.4% vs. 3.5% vs. 4.4% respectively; p 0.026), but similar after excluding patients with COVID-19 (4.5% vs. 3.5% vs. 4.4%; p 0.73). Cardiovascular mortality was similar between the study groups. After multivariable adjustment, admission for ACS during the COVID-19 outbreak had no impact on in-hospital mortality. In the case period, patients with concomitant ACS and Covid-19 experienced significantly higher in-hospital mortality (25% vs. 5%, p < 0.001) compared to patients without. Moreover, higher rates of cardiovascular death, cardiogenic shock and sustained ventricular tachycardia were found in Covid-19 patients. Conclusion: ACS patients presenting during the Covid-19 pandemic experienced increased all-cause mortality, driven by Covid-19 positive status due to higher rates of cardiogenic shock and sustained ventricular tachycardia. No differences in cardiovascular mortality compared to non-pandemic scenarios were reported

MELODI: Mining Enriched Literature Objects to Derive Intermediates

BackgroundThe scientific literature contains a wealth of information from different fields on potential disease mechanisms. However, identifying and prioritizing mechanisms for further analytical evaluation presents enormous challenges in terms of the quantity and diversity of published research. The application of data mining approaches to the literature offers the potential to identify and prioritize mechanisms for more focused and detailed analysis.MethodsHere we present MELODI, a literature mining platform that can identify mechanistic pathways between any two biomedical concepts.ResultsTwo case studies demonstrate the potential uses of MELODI and how it can generate hypotheses for further investigation. First, an analysis of ETS-related gene ERG and prostate cancer derives the intermediate transcription factor SP1, recently confirmed to be physically interacting with ERG. Second, examining the relationship between a new potential risk factor for pancreatic cancer identifies possible mechanistic insights which can be studied in vitro.ConclusionsWe have demonstrated the possible applications of MELODI, including two case studies. MELODI has been implemented as a Python/Django web application, and is freely available to use at [www.melodi.biocompute.org.uk]

Implantation of one, two or multiple MitraClips for transcatheter mitral valve repair: insights from a 1824-patient multicenter study

Transcatheter mitral valve repair (TMVR) with the MitraClip device is an established treatment for mitral regurgitation (MR). More than one MitraClip may be implanted if a single one does not reduce MR adequately. We aimed at appraising the outlook of patients undergoing implantation of one, two or multiple MitraClips for TMVR

Implantation of one, two or multiple MitraClip™ for transcatheter mitral valve repair: insights from a 1824-patient multicenter study

24noBACKGROUND: Transcatheter mitral valve repair (TMVR) with MitraClipTM (Abbott Laboratories; Abbott Park, IL, USA) is an established treatment for mitral regurgitation (MR). More than one MitraClipTM may be implanted if a single one does not reduce MR adequately. We aimed to appraise the outlook of patients undergoing implantation of one, two or multiple MitraClipTM for TMVR. METHODS: Exploiting the ongoing prospective GISE Registry of Transcatheter Treatment of Mitral Valve Regurgitation (GIOTTO) Study dataset, we compared patients, procedural details and outcomes distinguishing those receiving one, two or multiple MitraClipTM. The primary endpoint was the composite of 1-year cardiac death or rehospitalization for heart failure. Additional endpoints included all cause death, surgical mitral repair, and functional class. Multivariable adjusted Cox proportional hazard analysis was used for confirmatory purposes. RESULTS: As many as 1824 patients were included: 718 (39.4%) treated with a single MitraClipTM, and 940 (51.5%) receiving two MitraClipTM, and 166 (9.1%) receiving three or more. Significant differences were found for baseline features, including age, female gender, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, atrial fibrillation, permanent pacemaker, cardiac resynchronization therapy, implantable cardioverter defibrillator, and prior mitral valve repair (all P&lt;0.05). Several imaging features were also different, including left ventricular dimensions, MR severity and proportionality, mitral valve area, flail leaflet, and pulmonary vein flow (all P&lt;0.05). Among procedural features, significant differences were found for anesthesia type, MitraClipTM type, fluoroscopy, device, and operating room times, postprocedural mitral gradient, residual MR, smoke-like effect, device success partial detachment and surgical conversion (all P&lt;0.05). In-hospital death occurred more frequently in patients receiving multiple MitraClipTM, and the same applied severe residual MR (all P&lt;0.05). Mid-term follow-up (15 +/- 13 months) showed significant differences in the risk of death, cardiac death, rehospitalization for heart failure, and their composites, mainly, but not solely, associated with multiple MitraClipTM (all P&lt;0.05). Adjusted analysis confirmed the significantly increased risk of composite adverse events when comparing the multiple vs. single MitraClipTM groups (P=0.014 for death and rehospitalization, P=0.013 for cardiac death or rehospitalization). CONCLUSIONS: Implantation of one or two MitraClipTM is associated with favorable clinical outcomes. Conversely, bail-out implantation of three or more MitraClipTM may portend a worse long-term prognosis. (Cite this article as: Giordano A, Ferraro P, Finizio F, Biondi-Zoccai G, Denti P, Bedogni F, et al. Implantation of one, two or multiple MitraClipTM for transcatheter mitral valve repair: insights from a 1824-patient multicenter study. Panminerva Med 2022;64:1-8. DOI: 10.23736/S00310808.21.04497-9)noneGiordano, Arturo; Ferraro, Paolo; Finizio, Filippo; Biondi-Zoccai, Giuseppe; Denti, Paolo; Bedogni, Francesco; Rubbio, Antonio P; Petronio, Anna S; Bartorelli, Antonio L; Mongiardo, Annalisa; Giordano, Salvatore; DE Felice, Francesco; Adamo, Marianna; Montorfano, Matteo; Baldi, Cesare; Tarantini, Giuseppe; Giannini, Francesco; Ronco, Federico; Monteforte, Ida; Villa, Emmanuel; Ferrario, Maurizio; Fiocca, Luigi; Castriota, Fausto; Tamburino, CorradoGiordano, Arturo; Ferraro, Paolo; Finizio, Filippo; Biondi-Zoccai, Giuseppe; Denti, Paolo; Bedogni, Francesco; Rubbio, Antonio P; Petronio, Anna S; Bartorelli, Antonio L; Mongiardo, Annalisa; Giordano, Salvatore; DE Felice, Francesco; Adamo, Marianna; Montorfano, Matteo; Baldi, Cesare; Tarantini, Giuseppe; Giannini, Francesco; Ronco, Federico; Monteforte, Ida; Villa, Emmanuel; Ferrario, Maurizio; Fiocca, Luigi; Castriota, Fausto; Tamburino, Corrad

Identification of the MMS22L-TONSL complex that promotes homologous recombination

Budding yeast Mms22 is required for homologous recombination (HR)-mediated repair of stalled or broken DNA replication forks. Here we identify a human Mms22-like protein (MMS22L) and an MMS22L-interacting protein, NFκBIL2/TONSL. Depletion of MMS22L or TONSL from human cells causes a high level of double-strand breaks (DSBs) during DNA replication. Both proteins accumulate at stressed replication forks, and depletion of MMS22L or TONSL from cells causes hypersensitivity to agents that cause S phase-associated DSBs, such as topoisomerase (TOP) inhibitors. In this light, MMS22L and TONSL are required for the HR-mediated repair of replication fork-associated DSBs. In cells depleted of either protein, DSBs induced by the TOP1 inhibitor camptothecin are resected normally, but the loading of the RAD51 recombinase is defective. Therefore, MMS22L and TONSL are required for the maintenance of genome stability when unscheduled DSBs occur in the vicinity of DNA replication forks