Shared Genetic Liability across Systems of Psychiatric and Physical Illness.

Epidemiological literature has shown that there are extensive comorbidity patterns between psychiatric and physical illness. However, our understanding of the multivariate systems of relationships underlying these patterns is poorly understood. Using Genomic SEM and Genomic E-SEM, an extension for genomic exploratory factor analysis that we introduce and validate, we evaluate the extent to which latent genomic factors from eight domains, encompassing 76 physical outcomes across 1.9 million cases, evince genetic overlap with previously identified psychiatric factors. We find that internalizing, neurodevelopmental, and substance use factors are broadly associated with increased genetic risk sharing across all physical illness domains. Conversely, we find that a compulsive factor is protective against circulatory and metabolic illness, whereas genetic risk sharing between physical illness factors and psychotic/thought disorders was limited. Our results reveal pervasive risk sharing between specific groups of psychiatric and physical conditions and call into question the bifurcation of psychiatric and physical conditions.

Resolution of a chronic occipital wound with exposed skull bone with a fish skin graft: a successful treatment approach.

Chronic skin defects in the head, face and neck pose challenges for closure, especially after multiple surgeries or radiation therapy. We report the case of a woman in her 70s with a chronic occipital wound following squamous cell carcinoma resections, resulting in exposed skull bone. Despite various options, we successfully treated the 4 cm x 5 cm wound with a Kerecis fish skin graft (FSG), observing significant improvement within a week. The FSG promoted granulation tissue formation, enabling subsequent full-thickness skin grafting from the patient's groin. Complete wound closure was achieved within 2 weeks, indicating FSG's efficacy in complex wound management. Our experience highlights FSG's potential as a valuable tool in wound healing and reconstruction, particularly in challenging cases involving the head and neck.

[Artificial Intelligence in Head and Neck Surgery: Potentials, Challenges, and Ethical Considerations]. / Künstliche Intelligenz in der Kopf-Hals-Chirurgie: Potenziale und ethische Überlegungen.

BACKGROUND: The growing prominence of Artificial Intelligence (AI) in medicine introduces both transformative possibilities and potential challenges. Our study focuses on the current status and perceptions of AI in Head and Neck Surgery (HNS), examining its utilization, benefits, ethical concerns, and protective measures. OBJECTIVES: The study aims to illuminate the existing landscape of AI in HNS in Germany. MATERIALS AND METHODS: Conducted through a questionnaire, key aspects include its current usage, potential applications (e.g., diagnosis, surgical planning), anticipated benefits (e.g., improved patient care ), and significant ethical concerns (e.g., miscalculations by AI, data privacy). RESULTS: The survey reveals limited AI adoption in HNS, with substantial potential for improvement. Ethical considerations, especially miscalculations by AI and data privacy, emerge as central issues. The survey emphasizes the crucial role of physician control and the need for legal oversight to address concerns related to AI integration. While AI's presence in HNS is modest, the study identifies opportunities for enhancement. Ethical guidelines and practitioner-centric control are vital for discussions surrounding AI integration. CONCLUSIONS: This research underscores the significance of ethical considerations and practitioner control in the context of AI in surgical practices. It highlights the demand for targeted training to empower practitioners in navigating the complexities of AI technologies in healthcare, ensuring responsible and patient-centric implementation.

Perfusion in Pedicled Skin Flaps: Initial Insights from Smartphone-Based Thermal Imaging Protocol.

OBJECTIVE: Successful outcomes in head and neck surgery rely on maintaining perfusion in pedicled skin flaps. Thermal imaging offers a noninvasive means to assess tissue perfusion, potentially aiding in predicting flap viability. This pilot study explores the utility of SBTI (smartphone-based thermal imaging) for predicting flap vitality and monitoring during surgery. METHODS: Thermal imaging was employed using the FLIR One System. An imaging protocol was established, defining points of interest (T1-T4) on pedicled skin flaps. Conducted over four months, the study integrated SBTI into reconstructive surgery for the face, head and neck defects post-tumor resections. SBTI's effectiveness was assessed with n = 11 pedicled flaps, capturing images at key stages and correlating them with clinical flap assessment. Thermal images were retrospectively graded by two surgeons, evaluating flap perfusion on a scale from 1 to 5, based on temperature differences (1 = ΔT < 2 °C, 2 = ΔT ≥ 2 °C, 3 = ΔT ≥ 4 °C, 4 = ΔT ≥ 6 °C, and 5 = ΔT ≥ 8 °C), with assessments averaged for consensus and compared with the clinical assessment control group. RESULTS: The study encountered challenges during implementation, leading to the exclusion of six patients. Patient data included 11 cases with n = 44 SBTI images. Intraoperative assessments consistently showed good perfusion. One postoperative dehiscence was noted, which retrospectively coincided with intraoperative SBTI grading, but not with clinical assessment. Statistical analysis indicated consistent outcomes following clinical and SBTI assessments. Thermal imaging accurately predicted flap viability, although it had limitations with small flaps. CONCLUSION: SBTI proved effective, inexpensive, and noninvasive for assessing tissue perfusion, showing promise for predicting flap viability and intraoperative monitoring in head and neck surgery.

Examining the Genetic Links between Clusters of Immune-mediated Diseases and Psychiatric Disorders.

Importance: Autoimmune and autoinflammatory diseases have been linked to psychiatric disorders in the phenotypic and genetic literature. However, a comprehensive model that investigates the association between a broad range of psychiatric disorders and immune-mediated disease in a multivariate framework is lacking. Objective: This study aims to establish a factor structure based on the genetic correlations of immune-mediated diseases and investigate their genetic relationships with clusters of psychiatric disorders. Design Setting and Participants: We utilized Genomic Structural Equation Modeling (Genomic SEM) to establish a factor structure of 11 immune-mediated diseases. Genetic correlations between these immune factors were examined with five established factors across 13 psychiatric disorders representing compulsive, schizophrenia/bipolar, neurodevelopmental, internalizing, and substance use disorders. We included GWAS summary statistics of individuals of European ancestry with sample sizes from 1,223 cases for Addison's disease to 170,756 cases for major depressive disorder. Main Outcomes and Measures: Genetic correlations between psychiatric and immune-mediated disease factors and traits to determine genetic overlap. We develop and validate a new heterogeneity metric, Q Factor , that quantifies the degree to which factor correlations are driven by more specific pairwise associations. We also estimate residual genetic correlations between pairs of psychiatric disorders and immune-mediated diseases. Results: A four-factor model of immune-mediated diseases fit the data well and described a continuum from autoimmune to autoinflammatory diseases. The four factors reflected autoimmune, celiac, mixed pattern, and autoinflammatory diseases. Analyses revealed seven significant factor correlations between the immune and psychiatric factors, including autoimmune and mixed pattern diseases with the internalizing and substance use factors, and autoinflammatory diseases with the compulsive, schizophrenia/bipolar, and internalizing factors. Additionally, we find evidence of divergence in associations within factors as indicated by Q Factor . This is further supported by 14 significant residual genetic correlations between individual psychiatric disorders and immune-mediated diseases. Conclusion and Relevance: Our results revealed genetic links between clusters of immune-mediated diseases and psychiatric disorders. Current analyses indicate that previously described relationships between specific psychiatric disorders and immune-mediated diseases often capture broader pathways of risk sharing indexed by our genomic factors, yet are more specific than a general association across all psychiatric disorders and immune-mediated diseases.

Enantioselective Syntheses of 3,4-Dihydropyrans Employing Isochalcogenourea-Catalyzed Formal (4+2)-Cycloadditions of Allenoates.

We herein successfully demonstrate the use of chiral isochalcogenoureas as Lewis Base catalysts for a variety of (4+2)-cycloaddition reactions of allenoates and different Michael acceptors. In all cases the same structural key-motive, a dihydropyran with a (Z)-configurated exocyclic double bond could be accessed as the major regio- and diastereoisomer in an enantioselective manner. Furthermore, these chiral dihydropyrans were successfully engaged in different follow-up transformations.

Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy.

Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound Ru-STF31 in the glioblastoma cancer cell line, U87MG. Ru-STF31 targets nicotinamide phosphoribosyltransferase (NAMPT), an enzyme overexpressed in U87MG. Ru-STF31 is activated by red light irradiation and releases two photoproducts: the ruthenium cage and the cytotoxic inhibitor STF31. This study shows that Ru-STF31 can significantly decrease intracellular NAD+ levels in both normoxic (21% O2) and hypoxic (1% O2) U87MG cells. Strikingly, NAD+ depletion by light activation of Ru-STF31 in hypoxic U87MG cells could not be rescued by the addition of extracellular NAD+. Our data suggest an oxygen-dependent active role of the ruthenium photocage released by light activation.

Characterizing Genetic Pathways Unique to Autism Spectrum Disorder at Multiple Levels of Biological Analysis.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical patterns of social functioning and repetitive/restricted behaviors. ASD commonly co-occurs with ADHD and, despite their clinical distinctiveness, the two share considerable genetic overlap. Given their shared genetic liability, it is unclear which genetic pathways confer unique risk for ASD independent of ADHD. We applied Genomic Structural Equation Modeling (SEM) to GWAS summary statistics for ASD and ADHD, decomposing the genetic signal for ASD into that which is unique to ASD (uASD) and that which is shared with ADHD. We computed genetic correlations between uASD and 75 external traits to estimate genetic overlap between uASD and other clinically relevant phenotypes. We went on to apply Stratified Genomic SEM to identify classes of genes enriched for uASD. Finally, we implemented Transcriptome-Wide SEM (T-SEM) to explore patterns of gene-expression associated with uASD. We observed positive genetic correlations between uASD and several external traits, most notably those relating to cognitive/educational outcomes and internalizing psychiatric traits. Stratified Genomic SEM showed that heritability for uASD was significantly enriched in genes involved in evolutionarily conserved processes, as well as for a histone mark in the germinal matrix. T-SEM revealed 83 unique genes with expression associated with uASD, many of which were novel. These findings delineate the unique biological underpinnings of ASD which exist independent of ADHD and demonstrate the utility of Genomic SEM and its extensions for disambiguating shared and unique risk pathways for genetically overlapping traits.

Cell viability imaging in tumor spheroids via DNA binding of a ruthenium(II) light-switch complex.

The famous ''light-switch'' ruthenium complex [Ru(bpy)2(dppz)](PF6)2 (1) has been long known for its DNA binding properties in vitro. However, the biological utility of this compound has been hampered by its poor cellular uptake in living cells. Here we report a bioimaging application of 1 as cell viability probe in both 2D cells monolayer and 3D multi-cellular tumor spheroids of various human cancer cell lines (U87, HepG2, A549). When compared to propidium iodide, a routinely used cell viability probe, 1 was found to enhance the staining of dead cells in particular in tumor spheroids. 1 has high photostability, longer Stokes shift, and displays lower cytotoxicity compared to propidium iodide, which is a known carcinogenic. Finally, 1 was also found to displace the classical DNA binding dye Hoechst in dead cells, which makes it a promising dye for time-dependent imaging of dead cells in cell cultures, including multi-cellular tumor spheroids.

Treatment of Frey Syndrome with Botulinum Toxin-A: A Practical Approach from Minor's Test to Injection.

Introduction: Frey's syndrome, described by Lucy Frey in 1923, is a unique condition characterized by sweating, flushing, and reddening as a direct response to mastication. This phenomenon results from the aberrant regeneration of postganglionic parasympathetic neurons originating from the auriculotemporal nerve and the subsequent acetylcholine secretion induced by masticatory stimuli. Although rare, this syndrome can have multiple underlying causes and is frequently observed, occurring in up to 65% of cases following lateral parotid resections. Additionally, it can less commonly manifest after neck dissection, facelift procedures, or be associated with diabetes mellitus. Method: This article outlines a comprehensive diagnostic algorithm for Frey's syndrome, which includes the utilization of the Minor-Starch-Iodine Test. This test is a key component in diagnosing the syndrome and is discussed in detail, providing insights into its procedure and interpretation. Additionally, the gold standard of treatment for established Frey's syndrome, botulinum toxin A, is thoroughly described, including its mechanism of action, administration, and potential side effects. Discussion: Finally, the article underscores the need for further research to enhance our understanding of Frey's syndrome, leading to better diagnostic methods and more tailored treatment options for patients.

Age-Dependent RGS5 Loss in Pericytes Induces Cardiac Dysfunction and Fibrosis.

BACKGROUND: Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown. METHODS: In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes. Furthermore, we have conducted in vivo and in vitro analysis of RGS5 (regulator of G-protein signaling 5) loss of function and finally have performed pericytes-fibroblasts coculture studies to understand the effect of RGS5 deletion in pericytes on the neighboring fibroblasts. RESULTS: Aging reduced the pericyte area and capillary coverage in the murine heart. Single-nucleus RNA sequencing analysis further revealed that the expression of Rgs5 was reduced in cardiac pericytes from aged mice. In vivo and in vitro studies showed that the deletion of RGS5 impaired cardiac function, induced fibrosis, and morphological changes in pericytes characterized by a profibrotic gene expression signature and the expression of different ECM (extracellular matrix) components and growth factors, for example, TGFB2 and PDGFB. Indeed, culturing fibroblasts with the supernatant of RGS5-deficient pericytes induced their activation as evidenced by the increased expression of αSMA (alpha smooth muscle actin) in a TGFß (transforming growth factor beta)2-dependent mechanism. CONCLUSIONS: Our results have identified RGS5 as a crucial regulator of pericyte function during cardiac aging. The deletion of RGS5 causes cardiac dysfunction and induces myocardial fibrosis, one of the hallmarks of cardiac aging.

Improved integration of single-cell transcriptome data demonstrates common and unique signatures of heart failure in mice and humans.

BACKGROUND: Cardiovascular research heavily relies on mouse (Mus musculus) models to study disease mechanisms and to test novel biomarkers and medications. Yet, applying these results to patients remains a major challenge and often results in noneffective drugs. Therefore, it is an open challenge of translational science to develop models with high similarities and predictive value. This requires a comparison of disease models in mice with diseased tissue derived from humans. RESULTS: To compare the transcriptional signatures at single-cell resolution, we implemented an integration pipeline called OrthoIntegrate, which uniquely assigns orthologs and therewith merges single-cell RNA sequencing (scRNA-seq) RNA of different species. The pipeline has been designed to be as easy to use and is fully integrable in the standard Seurat workflow.We applied OrthoIntegrate on scRNA-seq from cardiac tissue of heart failure patients with reduced ejection fraction (HFrEF) and scRNA-seq from the mice after chronic infarction, which is a commonly used mouse model to mimic HFrEF. We discovered shared and distinct regulatory pathways between human HFrEF patients and the corresponding mouse model. Overall, 54% of genes were commonly regulated, including major changes in cardiomyocyte energy metabolism. However, several regulatory pathways (e.g., angiogenesis) were specifically regulated in humans. CONCLUSIONS: The demonstration of unique pathways occurring in humans indicates limitations on the comparability between mice models and human HFrEF and shows that results from the mice model should be validated carefully. OrthoIntegrate is publicly accessible (https://github.com/MarianoRuzJurado/OrthoIntegrate) and can be used to integrate other large datasets to provide a general comparison of models with patient data.

Chiral Isochalcogenourea-Catalysed Enantioselective (4+2) Cycloadditions of Allenoates.

Allenoates are versatile building blocks which are primarily activated and controlled using chiral tert. phosphine and tert. amine Lewis bases. We herein report the first example of allenoate activation by using chiral isochalcogenoureas (IChU) for formal (4+2) cycloaddition reactions. Compared to established phosphine and amine catalysis, the use of these easily available Lewis bases enables new stereoselective reaction pathways proceeding with high enantioselectivities, diastereoselectivities, and in good yields. In addition, the factors governing enantioselectivity and the origin of the observed differences compared to other commonly used Lewis bases are explained.

Structure and Internal Dynamics of Short RNA Duplexes Determined by a Combination of Pulsed EPR Methods and MD Simulations.

We used EPR spectroscopy to characterize the structure of RNA duplexes and their internal twist, stretch and bending motions. We prepared eight 20-base-pair-long RNA duplexes containing the rigid spin-label Çm, a cytidine analogue, at two positions and acquired orientation-selective PELDOR/DEER data. By using different frequency bands (X-, Q-, G-band), detailed information about the distance and orientation of the labels was obtained and provided insights into the global conformational dynamics of the RNA duplex. We used 19F Mims ENDOR experiments on three singly Çm- and singly fluorine-labeled RNA duplexes to determine the exact position of the Çm spin label in the helix. In a quantitative comparison to MD simulations of RNA with and without Çm spin labels, we found that state-of-the-art force fields with explicit parameterization of the spin label were able to describe the conformational ensemble present in our experiments. The MD simulations further confirmed that the Çm spin labels are excellent mimics of cytidine inducing only small local changes in the RNA structure. Çm spin labels are thus ideally suited for high-precision EPR experiments to probe the structure and, in conjunction with MD simulations, motions of RNA.

Hierarchical Assembly of Single-Stranded RNA.

Single-stranded RNA (ssRNA) plays a major role in the flow of genetic information-most notably, in the form of messenger RNA (mRNA)-and in the regulation of biological processes. The highly dynamic nature of chains of unpaired nucleobases challenges structural characterizations of ssRNA by experiments or molecular dynamics (MD) simulations alike. Here, we use hierarchical chain growth (HCG) to construct ensembles of ssRNA chains. HCG assembles the structures of protein and nucleic acid chains from fragment libraries created by MD simulations. Applied to homo- and heteropolymeric ssRNAs of different lengths, we find that HCG produces structural ensembles that overall are in good agreement with diverse experiments, including nuclear magnetic resonance (NMR), small-angle X-ray scattering (SAXS), and single-molecule Förster resonance energy transfer (FRET). The agreement can be further improved by ensemble refinement using Bayesian inference of ensembles (BioEn). HCG can also be used to assemble RNA structures that combine base-paired and base-unpaired regions, as illustrated for the 5' untranslated region (UTR) of SARS-CoV-2 RNA.

Rare encounter: facial vein thrombosis and thrombophlebitis as a complication of acute submandibular sialadenitis.

Thrombosis and thrombophlebitis of the facial vein represent exceptionally rare diagnoses, particularly when occurring as complications of acute sialadenitis of the submandibular gland. This case report details the experience of a middle-aged man initially presenting at a tertiary care ear, nose and throat department with right submandibular gland sialadenitis. Despite initiating outpatient treatment involving oral antibiotics and sialagogues, the patient returned after a week with persistent and worsening pain, accompanied by swelling of the right submandibular gland and cheek. Using ultrasound, the accurate diagnosis was promptly identified, revealing thrombosis in the facial vein.The patient underwent a comprehensive treatment regimen involving anticoagulation and intravenous antibiotics. With a subsequent reduction in pain and swelling, the patient was discharged, continuing oral anticoagulation and antibiotics. Outpatient follow-up revealed a complete recovery 3 weeks later. This case underscores the importance of timely and precise diagnostic measures in managing rare complications associated with sialadenitis.

HBV reactivation and clinical resolution in an isolated anti-HBc-positive patient during immune checkpoint inhibition.

BACKGROUND: Immune checkpoint inhibitor (ICI)-related liver injury is a growing concern as ICIs are increasingly used in cancer treatment regimens. Interestingly, ICIs have exhibited antiviral effects among patients with chronic hepatitis B virus (HBV). However, the underlying mechanisms remain unclear, and clinical data on patients with previous HBV infection/exposure and isolated anti-HBV core antibodies (IAHBcs) are lacking. METHODS: We report a case illustrating the dual effects of ICIs in a patient experiencing panlobular hepatitis and concurrent HBV reactivation. FINDINGS: A 68-year-old male patient positive for IAHBcs was admitted with panlobular hepatitis and HBV reactivation after receiving systemic chemotherapy (several months before admission) and ICI treatment (4 weeks before admission) subsequent to metastatic primary lung cancer (NSCLC stage IV). This was followed by a rapid and significant decrease of HBV DNA viral load before and during antiviral treatment. CONCLUSIONS: This unique case sheds light on the dynamics of ICI therapy in IAHBc-positive patients experiencing HBV reactivation during chemotherapy and underscores the dual impact of ICIs. Moreover, it emphasizes the need for assessment of HBV serology and prophylaxis in IAHBc-positive patients undergoing chemotherapy and ICI treatment. FUNDING: R.T.C. was supported by the MGH Research Scholars Program.

The Pictorial Fit-Frail Scale Malay Version (PFFS-M): Predictive Validity Testing in Malaysian Primary Care.

The purpose of this study was to evaluate the association between Pictorial Fit Frail Scale-Malay version (PFFS-M) and adverse outcomes, such as falls, new disability, hospitalisation, nursing home placement, and/or mortality, in patients aged 60 and older attending Malaysian public primary care clinics. We assessed the baseline PFFS-M levels of 197 patients contactable by phone at 18 months to determine the presence of adverse outcomes. 26 patients (13.2%) reported at least one adverse outcome, including five (2.5%) who fell, three (1.5%) who became disabled and homebound, 15 (7.6%) who were hospitalized, and three (1.5%) who died. Using binary multivariable logistic regression adjusted for age and gender, we found that patients who were at-risk of frailty and frail at baseline were associated with 5.97(95% CI [1.89-18.91]; P=0.002) and 6.13 (95% CI [1.86-20.24]; P= 0.003) times higher risk of developing adverse outcomes at 18 months, respectively, than patients who were not frail. The PFFS-M was associated with adverse outcomes.

Angina en pacientes con estenosis aórtica grave sometidos a implante percutáneo de la válvula aórtica / Angina in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

Introducción y objetivos: Evaluar la prevalencia, las características clínicas y el impacto de la angina en pacientes con estenosis aórtica sometidos a implante percutáneo de válvula aórtica (TAVI). Métodos: Se analizó a 1.687 pacientes consecutivos con estenosis aórtica sometidos a TAVI, clasificados en función de la presencia o ausencia basal de angina. Los datos basales, del procedimiento y del seguimiento se recogieron en una base de datos local. Resultados: Un total de 497 pacientes (29%) presentaban angina antes del TAVI. Los pacientes con angina basal presentaban peor clase funcional (NYHA> II, el 69% frente al 63%; p=0,017) y una mayor prevalencia de enfermedad coronaria (el 74% frente al 56%; p <0,001). La angina basal no mostró impacto pronóstico a 1 año en mortalidad por cualquier causa (HR=1,02; IC95%, 0,71-1,48; p=0,898) ni en mortalidad cardiovascular (HR=1,2; IC95%, 0,69-2,11; p=0,517). Sin embargo, la persistencia de angina 30 días después del procedimiento se asoció con un incremento en la mortalidad a 1 año, tanto total (HR=4,86; IC95%, 1,71-13,8; p=0,003) como de causa cardiovascular (HR=20,7; IC95%, 3,50-122,6; p=0,001). Conclusiones: Más de un cuarto de los pacientes con estenosis aórtica sometidos a TAVI tenían angina antes del procedimiento. La angina basal no mostró impacto pronóstico alguno. Sin embargo, la persistencia de angina 30 días después del procedimiento se asoció con una mayor mortalidad al año.(AU)

Introduction and objectives: To evaluate the prevalence, clinical characteristics, and outcomes of patients with angina undergoing transcatheter aortic valve replacement (TAVR) for severe aortic stenosis. Methods: A total of 1687 consecutive patients with severe aortic stenosis undergoing TAVR at our center were included and classified according to patient-reported angina symptoms prior to the TAVR procedure. Baseline, procedural and follow-up data were collected in a dedicated database. Results: A total of 497 patients (29%) had angina prior to the TAVR procedure. Patients with angina at baseline showed a worse New York Heart Association (NYHA) functional class (NYHA class> II: 69% vs 63%; P=.017), a higher rate of coronary artery disease (74% vs 56%; P <.001), and a lower rate of complete revascularization (70% vs 79%; P <.001). Angina at baseline had no impact on all-cause mortality (HR, 1.02; 95%CI, 0.71-1.48; P=.898) and cardiovascular mortality (HR, 1.2; 95%CI, 0.69-2.11; P=.517) at 1 year. However, persistent angina at 30 days post-TAVR was associated with increased all-cause mortality (HR, 4.86; 95%CI, 1.71-13.8; P=.003) and cardiovascular mortality (HR, 20.7; 95%CI, 3.50-122.6; P=.001) at 1-year follow-up. Conclusions: More than one-fourth of patients with severe aortic stenosis undergoing TAVR had angina prior to the procedure. Angina at baseline did not appear to be a sign of a more advanced valvular disease and had no prognostic impact; however, persistent angina at 30 days post-TAVR was associated with worse clinical outcomes.(AU)