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BACKGROUND AND PURPOSE: In ischemic stroke, leptomeningeal collaterals can provide delayed and dispersed compensatory blood flow to tissue-at-risk despite an occlusion and can impact treatment response and infarct growth. The purpose of this work is to test the hypothesis that inclusion of this delayed and dispersed flow with an appropriately calculated Local Arterial Input Function (Local-AIF) is needed to quantify the degree of collateral blood supply in tissue distal to an occlusion. MATERIALS AND METHODS: Seven experiments were conducted in a pre-clinical middle cerebral artery occlusion model. Dynamic susceptibility contrast MRI was imaged and post-processed to yield quantitative cerebral blood flow (qCBF) maps with both a traditionally chosen single arterial input function applied globally to the whole brain (i.e. "Global-AIF") and a delay and dispersion corrected AIF (i.e. "Local-AIF") that is sensitive to retrograde flow. Leptomeningeal collateral arterial recruitment was quantified with a pial collateral score from x-ray angiograms, and infarct growth calculated from serially acquired diffusion weighted MRI scans. RESULTS: The degree of collateralization at x-ray correlated more strongly with qCBF using the Local-AIF in the ischemic penumbra (R2=0.81) than traditionally chosen Global-AIF (R2=0.05). qCBF using a Local-AIF was negatively correlated (less infarct progression as perfusion increased) with infarct growth (R2 = 0.79) more strongly than a Global-AIF (R2=0.02). CONCLUSIONS: In acute stroke, qCBF calculated with a Local-AIF is more accurate for assessing tissue status and collateral supply than traditionally chosen Global-AIFs. These findings support use of a Local-AIF that corrects for delayed and dispersed retrograde flow in determining quantitative tissue perfusion with collateral supply in occlusive disease. ABBREVIATIONS: MRI = magnetic resonance imaging; DSC = dynamic susceptibility contrast; PCS = pial collateral score; MCAO = middle cerebral artery occlusion; MCA = middle cerebral artery; AIF = arterial input function; rCBF = relative cerebral blood flow; qCBF = quantitative cerebral blood flow.
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Background: Mastectomy poses significant challenges to a woman's body image and psychological well-being, and breast reconstruction plays a pivotal role in postoperative quality of life. Following breast reconstruction, many patients choose to have subsequent aesthetic procedures. Data on the prevalence of such subsequent aesthetic interventions are lacking in the literature. The aim of this study was to analyze trends in aesthetic procedures in patients following mastectomy with and without breast reconstruction. Methods: The PearlDiver database was queried within its capabilities for patients who underwent mastectomy with and without breast reconstruction, and a variety of aesthetic procedures after mastectomy. Aesthetic procedure rates were compared between cohorts. Results: We identified 365,525 mastectomy patients: 282,815 without reconstruction and 82,710 with reconstruction. In total, 609 patients with reconstruction and 329 without underwent subsequent aesthetic procedures. The rate of aesthetic procedures was higher in the reconstruction group (0.7%) compared with the nonreconstruction group (0.1%; P < 0.001). Conclusions: Patients who chose to have breast reconstruction after mastectomy underwent significantly more subsequent aesthetic procedures compared with those who chose mastectomy alone. Our findings provide insights on the prevalence of aesthetic procedures in postmastectomy patients, highlighting the potentially longitudinal nature of the reconstructive and aesthetic journey beyond the index oncologic procedure. Further research is needed to address motivations for such procedures as well as patient-reported outcomes and satisfaction.
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A siliceous material in which a framework order was established with a surfactant with sixteen carbon atoms in alkyl chains, MCM-41-C16, was synthesised, surface-modified, and tested regarding the selected physical properties. The pristine material was extracted in an acidic aqueous alcohol and then lined with different surface groups. The properties of four adsorbents were investigated using XRD, X-ray photoelectron spectroscopy, and N2 physisorption techniques. The unit-cell constant was determined from X-ray diffractograms, being in fixed relation to the edge length of the hexagonal frame. The specific surface areas of mesopores and whole crystallites were determined from low-temperature N2-physisorption isotherms. The novelty of this work is a mathematical model of a crystalline microstructure explaining the sizes and shapes of crystalline grains in relation to adsorption features, proposed and successfully tested with the aforementioned experimental data. The roughness of the surface is different from one that is necessary to explain the experimental characteristics quantitatively.
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Background and purpose: In ischemic stroke, leptomeningeal collaterals can provide compensatory blood flow to tissue at risk despite an occlusion, and impact treatment response and infarct growth. The purpose of this work is to test the hypothesis that local perfusion with an appropriate Local Arterial Input Function (AIF) is needed to quantify the degree of collateral blood supply in tissue distal to an occlusion. Materials and methods: Seven experiments were conducted in a pre-clinical middle cerebral artery occlusion model. Magnetic resonance dynamic susceptibility contrast (DSC) was imaged and post-processed as cerebral blood flow maps with both a traditionally chosen single arterial input function (AIF) applied globally to the whole brain (i.e. "Global-AIF") and a novel automatic delay and dispersion corrected AIF (i.e. "Local AIF") that is sensitive to retrograde flow. Pial collateral recruitment was assessed from x-ray angiograms and infarct growth via serially acquired diffusion weighted MRI scans both blinded to DSC. Results: The degree of collateralization at x-ray correlated strongly with quantitative perfusion determined using the Local AIF in the ischemic penumbra (R2=0.81) compared to a traditionally chosen Global-AIF (R2=0.05). Quantitative perfusion calculated using a Local-AIF was negatively correlated (less infarct progression as local perfusion increased) with infarct growth (R2 = 0.79) compared to Global-AIF (R2=0.02). Conclusions: Local DSC perfusion with a Local-AIF is more accurate for assessing tissue status and degree of leptomeningeal collateralization than traditionally chosen AIFs. These findings support use of a Local-AIF in determining quantitative tissue perfusion with collateral supply in occlusive disease.
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Psychedelics can profoundly alter cognition and consciousness. Their use in Middle Eastern countries, including Iraq, is ambiguous. We aim to investigate psychedelic awareness and use among Iraqi and Polish medical students. We surveyed 739 university students from Poland (315) and Iraq (424) using 31 adapted questions from the European School Survey Project on Alcohol and Other Drugs (ESPAD). We conducted multivariable analyses based on binary logistic regression to identify the factors associated with psychedelic awareness and use. Most of the respondents were females (65.6%) and senior medical students (69.6%). Notably, the Polish students displayed a higher prevalence of psychedelic use (21.6% compared to 1.2%, p < 0.001), while the Iraqi participants exhibited a lower familiarity with psychedelics (p < 0.001). The multivariable model demonstrated a commendable level of statistical accuracy and satisfactorily conformed to the Hosmer-Lemeshow goodness-of-fit test (statistical accuracy = 91.61%, Nagelkerke R2 = 0.488, p-value = 0.848). Several factors emerged as correlates of increased psychedelic use, including lacking an intact religious belief system or commitment to its practice (OR = 7.26, 95% CI [2.33, 22.60]). Additionally, those who perceived a low risk associated with sporadic psychedelic use (3.03, [1.44, 6.36]) were likelier to engage in such behavior. Other factors included residing in Poland (2.82, [0.83, 9.55]), maintaining positive attitudes toward psychedelics (2.49, [1.20, 5.14]), frequent social nightlife activities (2.41, [1.26, 4.61]), male gender (2.05, [1.10, 3.85]), and cigarette or tobacco smoking (2.03, [1.06, 3.86]). Significant disparities exist between Poles and Iraqis, influenced by religiosity, perceptions of the usage risks, geographical location, gender, attitudes toward psychedelics, parental leniency, and social freedom, especially concerning nightlife activities. Addressing the factors influencing psychedelic usage is paramount to responsible psychedelic engagement and culturally sensitive interventions to prevent misuse.
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BACKGROUND: Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout (GalT-KO) pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. In this study, we compare outcomes between autografts and cold preserved xenografts in a rat sciatic model of nerve gap repair. METHODS: Fifty male Lewis rats had a 1 cm sciatic nerve defect repaired using either: autograft and suture (n=10); 1-week or 4-week cold preserved xenograft and suture (n=10 per group); 1-week or 4-week cold preserved xenograft and photochemical tissue bonding using a human amnion wrap (PTB/HAM) (n=10 per group). Rats with xenografts were given tacrolimus until 4 months post-operatively. At 4 and 7 months, rats were euthanized and nerve sections harvested. Monthly sciatic functional index (SFI) scores were calculated. RESULTS: All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the 1-week cold preserved PTB/HAM group. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold preserved groups had significantly lower scores than the 4-week cold preserved suture group. CONCLUSIONS: Our results in the rat sciatic model suggest that GalT-KO nerve xenografts may be viable alternatives to autografts and demonstrate the need for further studies of long-gap repair and comparison with acellular nerve allografts. CLINICAL RELEVANCE: This proof-of-concept study in the rat sciatic model demonstrates that cold preserved GalT-KO porcine xenografts support axonal regeneration, as well as axonal viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.
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Mitosis involves intricate steps, such as DNA condensation, nuclear membrane disassembly, and phosphorylation cascades that temporarily halt gene transcription. Despite this disruption, daughter cells remarkably retain the parent cell's gene expression pattern, allowing for efficient transcriptional memory after division. Early studies in mammalian cells suggested that transcription factors (TFs) mark genes for swift reactivation, a phenomenon termed 'mitotic bookmarking', but conflicting data emerged regarding TF presence on mitotic chromosomes. Recent advancements in live-cell imaging and fixation-free genomics challenge the conventional belief in universal formaldehyde fixation, revealing dynamic TF interactions during mitosis. Here, we review recent studies that provide examples of at least four modes of TF-DNA interaction during mitosis and the molecular mechanisms that govern these interactions. Additionally, we explore the impact of these interactions on transcription initiation post-mitosis. Taken together, these recent studies call for a paradigm shift toward a dynamic model of TF behavior during mitosis, underscoring the need for incorporating dynamics in mechanistic models for re-establishing transcription post-mitosis.
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Mitosis , Factores de Transcripción , Transcripción Genética , Humanos , Factores de Transcripción/metabolismo , Animales , ADN/metabolismo , Regulación de la Expresión GénicaRESUMEN
Introduction Patient-reported outcome measurements (PROMs) are gaining considerable popularity as tools to assess the effectiveness of the treatment in plastic surgery, being a complement to surgical outcomes. The SCAR-Q questionnaire has been recently developed for patients with surgical, traumatic, and burn scars. Aim The study aims to describe the process of translation and linguistic validation of the scar questionnaire (SCAR-Q) for use in Polish patients undergoing scar treatment. Material and methods An official Polish translation and language validation of the SCAR-Q were done in adherence to International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. The process consisted of four steps: two independent forward translations, a back translation, a review of the back translation, and cognitive participant interviews. Results The field-tested version of the SCAR-Q consisted of 29 items across three scales measuring appearance concerns, symptoms, and the psychosocial impact of the scar. The forward translation was done by two independent translators and revealed specific difficulties in translation to the Polish language (4/29 items). The back translation showed no significant differences compared to the original English version. Cognitive debriefing interviews involved nine Polish patients with postraumatic scars, burn scars, and scars after skin tumor resection. Participants have not reported any major difficulties in understanding the content of the questionnaire. Conclusions The ISPOR provides a straightforward and thorough guideline for the PROMs translation process. The new SCAR-Q is an accessible and efficient PROM that can be implemented in Polish patients to assess the effectiveness of scar treatment.
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Lower Respiratory Tract Infections (LRTIs) represent the leading cause of death due to infectious diseases. Current diagnostic modalities primarily depend on clinical symptoms and lack specificity, especially in light of common colonization without overt infection. To address this, we developed a noninvasive diagnostic approach that employs BreathBiomics™, an advanced human breath sampling system, to detect protease activities induced by bacterial infection in the lower respiratory tract. Specifically, we engineered a high-sensitivity and high-specificity molecular sensor for human neutrophil elastase (HNE). The sensor undergoes cleavage in the presence of HNE, an event that is subsequently detected via Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). Application of this methodology to clinical samples, breath specimens collected from intubated patients with LRTIs, demonstrated the detection of the cleaved sensor by MALDI-TOF MS. Our findings indicate that this novel approach offers a noninvasive and specific diagnostic strategy for people with LRTIs.
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Crystal methamphetamine, a potent psychostimulant, presents a complex clinical landscape. However, insights into the predisposing factors for suicidal tendencies among Iraqi users remain limited. Our study delves into these risks among 165 patients. Rigorous multivariable analysis was conducted, employing binary logistic regression, drawing from patients from Baghdad Medical City and Ibn-Rushd Teaching Hospital. Most participants were in their third decade (26.62 ± 0.53 years). Regarding suicidal ideation, our model demonstrated robust accuracy, supported by the Hosmer-Lemeshow goodness-of-fit test (NagelKerke's R2 = 0.49, accuracy = 79.4%, p = 0.885). Notably, chronic methamphetamine use exceeding a year (OR = 6.15, p = 0.001), absence of psychological trauma (OR = 4.58, p = 0.006), and incidence of visual hallucinations (OR = 4.52, p = 0.001) rendered users more susceptible to suicidal ideation. Furthermore, our investigation unveiled risk factors tied to psychotic features and withdrawal manifestations. The study underscores pivotal predictors of suicidal ideation, warranting interdisciplinary vigilance from psychiatrists, clinical psychologists, and social workers. By monitoring at-risk individuals, progression toward the intricate spectrum of suicide can be potentially averted. These findings illuminate the urgency of tailored interventions for crystal methamphetamine users, contributing to enhanced holistic care.
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Human visual experience usually provides ample opportunity to accumulate knowledge about events unfolding in the environment. In typical scene perception experiments, however, participants view images that are unrelated to each other and, therefore, they cannot accumulate knowledge relevant to the upcoming visual input. Consequently, the influence of such knowledge on how this input is processed remains underexplored. Here, we investigated this influence in the context of gaze control. We used sequences of static film frames arranged in a way that allowed us to compare eye movements to identical frames between two groups: a group that accumulated prior knowledge relevant to the situations depicted in these frames and a group that did not. We used a machine learning approach based on hidden Markov models fitted to individual scanpaths to demonstrate that the gaze patterns from the two groups differed systematically and, thereby, showed that recently accumulated prior knowledge contributes to gaze control. Next, we leveraged the interpretability of hidden Markov models to characterize these differences. Additionally, we report two unexpected and interesting caveats of our approach. Overall, our results highlight the importance of recently acquired prior knowledge for oculomotor control and the potential of hidden Markov models as a tool for investigating it.
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Movimientos Oculares , Aprendizaje Automático , Humanos , Películas Cinematográficas , SensaciónRESUMEN
The visual input that the eyes receive usually contains temporally continuous information about unfolding events. Therefore, humans can accumulate knowledge about their current environment. Typical studies on scene perception, however, involve presenting multiple unrelated images and thereby render this accumulation unnecessary. Our study, instead, facilitated it and explored its effects. Specifically, we investigated how recently-accumulated prior knowledge affects gaze behavior. Participants viewed sequences of static film frames that contained several 'context frames' followed by a 'critical frame'. The context frames showed either events from which the situation depicted in the critical frame naturally followed, or events unrelated to this situation. Therefore, participants viewed identical critical frames while possessing prior knowledge that was either relevant or irrelevant to the frames' content. In the former case, participants' gaze behavior was slightly more exploratory, as revealed by seven gaze characteristics we analyzed. This result demonstrates that recently-gained prior knowledge reduces exploratory eye movements.
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Movimientos Oculares , Fijación Ocular , Humanos , Ojo , Percepción VisualRESUMEN
The laboratory rat, Rattus norvegicus, is an important model of human health and disease, and experimental findings in the rat have relevance to human physiology and disease. The Rat Genome Database (RGD, https://rgd.mcw.edu) is a model organism database that provides access to a wide variety of curated rat data including disease associations, phenotypes, pathways, molecular functions, biological processes, cellular components, and chemical interactions for genes, quantitative trait loci, and strains. We present an overview of the database followed by specific examples that can be used to gain experience in employing RGD to explore the wealth of functional data available for the rat and other species. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Navigating the Rat Genome Database (RGD) home page Basic Protocol 2: Using the RGD search functions Basic Protocol 3: Searching for quantitative trait loci Basic Protocol 4: Using the RGD genome browser (JBrowse) to find phenotypic annotations Basic Protocol 5: Using OntoMate to find gene-disease data Basic Protocol 6: Using MOET to find gene-ontology enrichment Basic Protocol 7: Using OLGA to generate gene lists for analysis Basic Protocol 8: Using the GA tool to analyze ontology annotations for genes Basic Protocol 9: Using the RGD InterViewer tool to find protein interaction data Basic Protocol 10: Using the RGD Variant Visualizer tool to find genetic variant data Basic Protocol 11: Using the RGD Disease Portals to find disease, phenotype, and other information Basic Protocol 12: Using the RGD Phenotypes & Models Portal to find qualitative and quantitative phenotype data and other rat strain-related information Basic Protocol 13: Using the RGD Pathway Portal to find disease and phenotype data via molecular pathways.
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Genómica , Sitios de Carácter Cuantitativo , Humanos , Animales , Ratas , Bases de Datos de Proteínas , Fenotipo , OligopéptidosRESUMEN
Aboriginals of Latin America have used DMT (N,N-dimethyltryptamine) in ritualistic ceremonies for centuries. Nevertheless, there are limited data on web users' interest concerning DMT. We aim to review the literature and explore the spatial-temporal mapping of online search behavior concerning DMT, 5-MeO-DMT, and the Colorado River toad via Google Trends over the past 10 years (2012-2022) while using 5 search terms: "N,N-dimethyltryptamine", "5-methoxy-N,N-dimethyltryptamine", "5-MeO-DMT", "Colorado River toad", and "Sonoran Desert toad". Literature analysis conveyed novel information concerning DMT's past shamanic and present-day illicit uses, showcased experimental trials on DMT uses for neurotic disorders, and highlighted potential uses in modern medicine. DMT's geographic mapping signals originated mainly from Eastern Europe, the Middle East, and Far East Asia. In contrast, 5-MeO-DMT signals prevailed in Western Europe, Indo-China, and Australasia. Signals concerning the toad originated from the Americas, Australia, India, the Philippines, and Europe. Web users searched the most for "N,N-dimethyltryptamine" and "5-MeO-DMT". Three terms exhibited significant upgoing linear temporal trends: "5-MeO-DMT" (ß = 0.37, p < 0.001), "Sonoran Desert toad" (ß = 0.23, p < 0.001), and "Colorado River toad" (ß = 0.17, p < 0.001). The literature and Infoedemiology data provided crucial information concerning DMT's legal status, risks and benefits, and potential for abuse. Nonetheless, we opine that in the upcoming decades, physicians might use DMT to manage neurotic disorders pending a change in its legal status.
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BACKGROUND: The benefit of repair over replacement of rheumatic or calcified mitral valve (MV) is debatable. METHODS: Patients who underwent MV repair or replacement for rheumatic or calcified MV disease between 2006 and 2020 were identified in the Polish National Registry of Cardiac Surgery Procedures. Patients who underwent additional procedures other than coronary artery bypass grafting or tricuspid valve surgery, as well as redo or emergency cases, were excluded. The long-term survival was verified based on National Health Fund registry data. The survival was compared between MV repair and replacement in the whole cohort and after propensity score matching. RESULTS: We included 4338 patients: 1859 (43%) with pure mitral regurgitation and 2479 (57%) with mitral stenosis. MV was repaired in 543 patients (29%) with pure regurgitation and 126 (5.1%) with stenosis (P < .001). In total, 984 (23%) patients underwent concomitant coronary artery bypass grafting and 1358 (32%) tricuspid valve surgery. MV repair improved survival (hazard ratio 0.81; 95% CI 0.68-0.97; P = .022) in patients with no mitral stenosis, and had no effect in mitral stenosis (hazard ratio 1.17; 95% CI 0.85-1.59; P = .332). The results were confirmed in propensity-matched cohorts. The freedom from MV reoperation at 10 years was 95.5% ± 1.2% after repair and 96.0% ± 0.7% after MV replacement (P = .416) in the absence of stenosis and 91.8% ± 3.4% after repair vs 95.9% ± 0.5% after replacement in patients with mitral stenosis (P = .065). CONCLUSIONS: Repair of rheumatic/calcified mitral valve should be a preferred option in patients with no mitral stenosis, but confers no benefit if mitral stenosis is present.
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Humans constantly move their eyes to explore the environment. However, how image-computable features and object representations contribute to eye-movement control is an ongoing debate. Recent developments in object perception indicate a complex relationship between features and object representations, where image-independent object knowledge generates objecthood by reconfiguring how feature space is carved up. Here, we adopt this emerging perspective, asking whether object-oriented eye movements result from gaze being guided by image-computable features, or by the fact that these features are bound into an object representation. We recorded eye movements in response to stimuli that initially appear as meaningless patches but are experienced as coherent objects once relevant object knowledge has been acquired. We demonstrate that fixations on identical images are more object-centered, less dispersed, and more consistent across observers once these images are organized into objects. Gaze guidance also showed a shift from exploratory information sampling to exploitation of object-related image areas. These effects were evident from the first fixations onwards. Importantly, eye movements were not fully determined by knowledge-dependent object representations but were best explained by the integration of these representations with image-computable features. Overall, the results show how information sampling via eye movements is guided by a dynamic interaction between image-computable features and knowledge-driven perceptual organization. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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Movimientos Oculares , Percepción Visual , HumanosRESUMEN
BACKGROUND: Post-acute myocardial infarction papillary muscle rupture (post-AMI PMR) may present variable clinical scenarios and degree of emergency due to result of cardiogenic shock. Veno-arterial extracorporeal life support (V-A ECLS) has been proposed to improve extremely poor pre- or postoperative conditions. Information in this respect is scarce. METHODS: From the CAUTION (meChanical complicAtion of acUte myocardial infarcTion: an InternatiOnal multiceNter cohort study) database (16 different Centers, data from 2001 to 2018), we extracted adult patients who were surgically treated for post-AMI PMR and underwent pre- or/and postoperative V-A ECLS support. The end-points of this study were in-hospital survival and ECLS complications. RESULTS: From a total of 214 post-AMI PMR patients submitted to surgery, V-A ECLS was instituted in 23 (11%) patients. The median age was 61.7 years (range 46-81 years). Preoperatively, ECLS was commenced in 10 patients (43.5%), whereas intra/postoperative in the remaining 13. The most common V-A ECLS indication was post-cardiotomy shock, followed by preoperative cardiogenic shock and cardiac arrest. The median duration of V-A ECLS was 4 days. V-A ECLS complications occurred in more than half of the patients. Overall, in-hospital mortality was 39.2% (9/23), compared to 22% (42/219) for the non-ECLS group. CONCLUSIONS: In post-AMI PMR patients, V-A ECLS was used in almost 10% of the patients either to promote bridge to surgery or as postoperative support. Further investigations are required to better evaluate a potential for increased use and its effects of V-A ECLS in such a context based on the still high perioperative mortality.
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Cardiomiopatías , Oxigenación por Membrana Extracorpórea , Enfermedades de las Válvulas Cardíacas , Infarto del Miocardio , Adulto , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Oxigenación por Membrana Extracorpórea/métodos , Choque Cardiogénico/etiología , Choque Cardiogénico/cirugía , Estudios de Cohortes , Músculos Papilares/cirugía , Infarto del Miocardio/complicaciones , Cardiomiopatías/complicaciones , Enfermedades de las Válvulas Cardíacas/complicacionesRESUMEN
BACKGROUND: Referral and admission echocardiography (ECHO) in patients scheduled for aortic valve replacement (AVR) with aortic stenosis (AS) may differ in the assessment of moderate functional mitral regurgitation (FMR). AIMS: Our study was to determine the truly moderate-FMR and evaluate its impact on survival. METHODS: We conducted an observational study of patients referred for AVR with AS and up to moderate FMR, between 2014 and 2019. Patients were divided into three groups: (1) no/mild (N-FMR); (2) moderate-FMR on one ECHO (either at referral or admission) termed incidental (I-FMR); (3) moderate FMR in two studies (both at referral and admission) termed permanent (PM-FMR). RESULTS: The referral and admission assessment were performed median 35 days apart. Of the 679 elective patients who underwent elective isolated AVR, 516 patients had N-FMR, 102 patients had I-FMR, and 61 patients had PM-FMR. Median follow-up was 46 months (22.5-58.5); max 73.3. 30-day mortality was 2.5% vs. 1% vs. 8.2% (N-FMR vs. I-FMR vs. PM-FMR, respectively; P = 0.01). Five-year survival was 84.1% in N-FMR vs. 88.5% in I-FMR vs. 60.6% in PM-FMR group, where was the lowest (P <0.001). In multivariable modeling PM-FMR increased mortality (hazard ratio [HR], 1.88 [1.05-3.37]; P = 0.03). The I-FMR had no effect on mortality (HR, 0.67 [0.32-1.37]; P = 0.28). Five-year survival after excluding 30-day mortality was 86.3% vs. 89.4% vs. 66.0%; (N-FMR vs. I-FMR vs. PM-FMR, respectively; P = 0.02). The PM-FMR increased late mortality (HR, 2.17 [1.14-4.15]; P = 0.01). CONCLUSIONS: In patients undergoing isolated AVR for AS, the presence of permanent moderate FMR significantly impacts 30-day and mid-term survival.