Integrative metabolome and transcriptome analysis characterized methyl jasmonate-elicited flavonoid metabolites of Blumea balsamifera.

As a commonly used medicinal plant, the flavonoid metabolites of Blumea balsamifera and their association with genes are still elusive. In this study, the total flavonoid content (TFC), flavonoid metabolites and biosynthetic gene expression patterns of B. balsamifera after application of exogenous methyl jasmonate (MeJA) were scrutinized. The different concentrations of exogenous MeJA increased the TFC of B. balsamifera leaves after 48 h of exposure, and there was a positive correlation between TFC and the elicitor concentration. A total of 48 flavonoid metabolites, falling into 10 structural classes, were identified, among which flavones and flavanones were predominant. After screening candidate genes by transcriptome mining, the comprehensive analysis of gene expression level and TFC suggested that FLS and MYB may be key genes that regulate the TFC in B. balsamifera leaves under exogenous MeJA treatment. This study lays a foundation for elucidating flavonoids of B. balsamifera, and navigates the breeding of flavonoid-rich B. balsamifera varieties.

Janus kinase inhibitors and adverse events of acne in dermatologic indications: a systematic review and network meta-analysis.

Background: The occurrence of acne in patients treated with Janus kinase (JAK) inhibitors for skin diseases is a potential issue, which may reduce treatment adherence.Purpose: To systematically analyzes randomized clinical trials (RCTs) of JAK inhibitors in dermatological indications for the risk of acne as an adverse event.Methods: A meta-analysis of odds ratios (ORs) for acne incidence was conducted. Data were quantitatively synthesized using random-effects meta-analysis. Surface under the cumulative ranking curve (SUCRA) values representing the relative ranking probabilities of treatments were obtained. Analyses were performed using R statistical software version 4.4.0.Results: A total of 11,396 patients were included from 24 studies. The incidence of acne for JAK inhibitors was ranked according to the SUCRA as follows: JAK1 inhibitors > TYK2 inhibitors > combined JAK1 and JAK2 inhibitors > combined JAK1 and TYK2 inhibitors > JAK3 + TEC inhibitors > pan-JAK inhibitors. ORs were higher for longer durations of drug use and larger dosages. Subgroup analyses by disease indication revealed increased ORs for psoriasis (5.52 [95% CI, 1.39-21.88]), vitiligo (4.15 [95% CI, 1.27-13.58]), alopecia areata (3.86 [95% CI, 1.58-9.42]), and atopic dermatitis (2.82 [95% CI, 1.75-4.54]). The use of JAK inhibitors in patients with systemic lupus erythematosus (SLE) may not significantly increase the incidence of acne.Conclusions: There are higher rates of acne following treatment with JAK inhibitors for dermatologic indications, particularly with longer durations and larger dosages. Pan-JAK inhibitors exhibit the lowest incidence of acne.

Accurate Prediction of Rat Acute Oral Toxicity and Reference Dose for Thousands of Polycyclic Aromatic Hydrocarbon Derivatives Based on Chemometric QSAR and Machine Learning.

Acute oral toxicity is currently not available for most polycyclic aromatic hydrocarbons (PAHs), especially their derivatives, because it is cost-prohibitive to experimentally determine all of them. Here, quantitative structure-activity relationship (QSAR) models using machine learning (ML) for predicting the toxicity of PAH derivatives were developed, based on oral toxicity data points of 788 individual substances of rats. Both the individual ML algorithm gradient boosting regression trees (GBRT) and the stacking ML algorithm (extreme gradient boosting + GBRT + random forest regression) provided the best prediction results with satisfactory determination coefficients for both cross-validation and the test set. It was found that those PAH derivatives with fewer polar hydrogens, more large-sized atoms, more branches, and lower polarizability have higher toxicity. Software based on the optimal ML-QSAR model was successfully developed to expand the application potential of the developed model, obtaining reliable prediction of pLD50 values and reference doses for 6893 external PAH derivatives. Among these chemicals, 472 were identified as moderately or highly toxic; 10 out of them had clear environment detection or use records. The findings provide valuable insights into the toxicity of PAHs and their derivatives, offering a standard platform for effectively evaluating chemical toxicity using ML-QSAR models.

Prognostic effect of the TyG index on patients with severe aortic stenosis following transcatheter aortic valve replacement: a retrospective cohort study.

BACKGROUND: The triglyceride glucose (TyG) index, as a reliable marker of insulin resistance, is associated with the incidence and poor prognosis of various cardiovascular diseases. However, the relationship between the TyG index and clinical outcomes in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) remains unclear. METHODS: This study consecutively enrolled 1569 patients with AS underwent TAVR at West China Hospital of Sichuan University between April 2014 and August 2023. The outcomes of interest included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Multivariate adjusted Cox regression and restricted cubic splines (RCS) regression analyses were used to assess the associations between the TyG index and the clinical outcomes. The incremental prognostic value of the TyG index was further assessed by the time-dependent Harrell's C-index, integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: During a median follow-up of 1.09 years, there were 146, 70, and 196 patients experienced all-cause death, cardiovascular death, and MACE, respectively. After fully adjusting for confounders, a per-unit increase of TyG index was associated with a 441% (adjusted HR: 5.41, 95% CI: 4.01-7.32), 385% (adjusted HR: 4.85, 95% CI: 3.16-7.43), and 347% (adjusted HR: 4.47, 95% CI: 3.42-5.85) higher risk of all-cause mortality, cardiovascular mortality and MACE, respectively. The RCS regression analyses revealed a linear association between TyG index and endpoints (all P for non-linearity > 0.05) with 8.40 as the optimal binary cutoff point. Furthermore, adding TyG index to the basic risk model provided a significant incremental value in predicting poor prognosis (Time-dependent Harrell's C-index increased for all the endpoints; All-cause mortality, IDI: 0.11, P < 0.001; NRI: 0.32, P < 0.001; Cardiovascular mortality, IDI: 0.043, P < 0.001; NRI: 0.37, P < 0.001; MACE, IDI: 0.092, P < 0.001; NRI: 0.32, P < 0.001). CONCLUSIONS: In patients with severe AS receiving TAVR, there was a positive linear relationship between TyG index and poor prognosis, with 8.4 as the optimal bivariate cutoff value. Our findings suggest TyG index holds potential value for risk stratification and guiding therapeutic decisions in patients after TAVR.

The effect of high-volume intraoperative fluid administration on outcomes among pediatric patients undergoing living donor liver transplantation.

BACKGROUND: Pediatric patients undergoing liver transplantation are particularly susceptible to complications arising from intraoperative fluid management strategies. Conventional liberal fluid administration has been challenged due to its association with increased perioperative morbidity. This study aimed to assess the impact of intraoperative high-volume fluid therapy on pediatric patients who are undergoing living donor liver transplantation (LDLT). METHODS: Conducted at the Children's Hospital of Chongqing Medical University from March 2018 to April 2021, this retrospective study involved 90 pediatric patients divided into high-volume and non-high-volume fluid administration groups based on the 80th percentile of fluid administered. We collected the perioperative parameters and postoperative information of two groups. Multivariable logistic regression was utilized to assess the association between estimated blood loss (EBL) and high-volume FA. Kaplan-Meier survival analysis was used to compare patient survival after pediatric LDLT. RESULTS: Patients in the high-volume FA group received a higher EBL and longer length of stay than that in the non-high-volume FA group. Multivariate logistic regression analysis indicated that hours of maintenance fluids and fresh frozen plasma were significantly associated risk factors for the occurrence of EBL during pediatric LDLT. In addition, survival analysis showed no significant differences in one-year mortality between the groups. CONCLUSIONS: High-volume fluid administration during LDLT is linked with poorer intraoperative and postoperative outcomes among pediatric patients. These findings underscore the need for more conservative fluid management strategies in pediatric liver transplantations to enhance recovery and reduce complications.

Heterogeneous body compositions and all-cause mortality in acute coronary syndrome patients: a ten-year retrospective cohort study.

BACKGROUND: The association of different body components, including lean mass and body fat, with the risk of death in acute coronary syndrome (ACS) patients are unclear. METHODS: We enrolled adults diagnosed with ACS at our center between January 2011 and December 2012 and obtained follow-up outcomes via telephone questionnaires. We used restricted cubic splines (RCS) with the Cox proportional hazards model to analyze the associations between body mass index (BMI), predicted lean mass index (LMI), predicted body fat percentage (BF), and the value of LMI/BF with 10-year mortality. We also examined the secondary outcome of death during hospitalization. RESULTS: During the maximum 10-year follow-up of 1398 patients, 331 deaths (23.6%) occurred, and a U-shaped relationship was found between BMI and death risk (P nonlinearity = 0.03). After adjusting for age and history of diabetes, the overweight group (24 ≤ BMI < 28 kg/m2) had the lowest mortality (HR = 0.53, 95% CI: 0.29-0.99). Predicted LMI and LMI/BF had an inverse linear relationship with a 10-year death risk (P nonlinearity = 0.24 and P nonlinearity = 0.38, respectively), while an increase in BF was associated with increased mortality (P nonlinearity = 0.64). During hospitalization, 31 deaths (2.2%) were recorded, and the associations of the indicators with in-hospital mortality were consistent with the long-term outcome analyses. CONCLUSION: Our study provides new insight into the "obesity paradox" in ACS patients, highlighting the importance of considering body composition heterogeneity. Predicted LMI and BF may serve as useful tools for assessing nutritional status and predicting the prognosis of ACS, based on their linear associations with all-cause mortality.

Merging Ring-Opening 1,2-Metallate Shift with Asymmetric C(sp3)-H Borylation of Aziridines.

Chiral secondary alkyl amines with a vicinal quaternary stereocenter are undoubtedly important and ubiquitous subunits in natural products and pharmaceuticals. However, their asymmetric synthesis remains a formidable challenge. Herein, we merge the ring-opening 1,2-metallate shift with iridium-catalyzed enantioselective C(sp3)-H borylation of aziridines to deliver these frameworks with high enantioselectivities. We also demonstrated the synthetic application by downstream transformations, including the total synthesis of two Amaryllidaceae alkaloids, (-)-crinane and (+)-mesmebrane.

Psychosocial Factors Associated With Long-Term Cognitive Impairment Among COVID-19 Survivors: A Cross-Sectional Study.

ABSTRACT: COVID-19 survivors complained of the experience of cognitive impairments, which also called "brain fog" even recovered. The study aimed to describe long-term cognitive change and determine psychosocial factors in COVID-19 survivors. A cross-sectional study was recruited 285 participants from February 2020 to April 2020 in 17 hospitals in Sichuan Province. Cognitive function, variables indicative of the virus infection itself, and psychosocial variables were collected by telephone interview. Univariate logistic regression and Lasso logistic regression models were used for variable selection which plugged into a multiple logistics model. Overall prevalence of moderate or severe cognitive impairment was 6.3%. Logistic regression showed that sex, religion, smoking status, occupation, self-perceived severity of illness, sleep quality, perceived mental distress after COVID-19, perceived discrimination from relatives and friends, and suffered abuse were associated with cognitive impairment. The long-term consequences of cognitive function are related to multiple domains, in which psychosocial factors should be taken into consideration.

High-throughput single-molecule long-read RNA sequencing analysis of tissue-specific genes and isoforms in lettuce (Lactuca sativa L.).

Lettuce is one of the most widely cultivated and consumed dicotyledonous vegetables globally. Despite the availability of its reference genome sequence, lettuce gene annotation remains incomplete, impeding comprehensive research and the broad application of genomic resources. Long-read RNA isoform sequencing (Iso-Seq) offers substantial advantages for analyzing RNA alternative splicing and aiding gene annotation, yet it faces throughput limitations. We present the HIT-ISOseq method tailored for bulk sample analysis, significantly enhancing RNA sequencing throughput on the PacBio platform by concatenating cDNA. Here we show, HIT-ISOseq generates 3-4 cDNA molecules per CCS read in lettuce, yielding 15.7 million long reads per PacBio Sequel II SMRT Cell 8 M. We validate its effectiveness in analyzing six lettuce tissue samples, including roots, stems, and leaves, revealing tissue-specific gene expression patterns and RNA isoforms. Leveraging diverse tissue long-read RNA sequencing, we refine the transcript annotation of the lettuce reference genome, expanding its GO and KEGG annotation repertoire. Collectively, this study serves as a foundational reference for genome annotation and the analysis of multi-sample isoform expression, utilizing high-throughput long-read transcriptome sequencing.

Patient-Specific Factors Predicting Renal Denervation Response in Patients With Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: The accurate selection of patients likely to respond to renal denervation (RDN) is crucial for optimizing treatment outcomes in patients with hypertension. This systematic review was designed to evaluate patient-specific factors predicting the RDN response. METHODS AND RESULTS: We focused on individuals with hypertension who underwent RDN. Patients were categorized based on their baseline characteristics. The primary outcome was blood pressure (BP) reduction after RDN. Both randomized controlled trials and nonrandomized studies were included. We assessed the risk of bias using corresponding tools and further employed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the overall quality of evidence. A total of 50 studies were ultimately included in this systematic review, among which 17 studies were for meta-analysis. Higher baseline heart rate and lower pulse wave velocity were shown to be associated with significant antihypertensive efficacy of RDN on 24-hour systolic BP reduction (weighted mean difference, -4.05 [95% CI, -7.33 to -0.77]; weighted mean difference, -7.20 [95% CI, -9.79 to -4.62], respectively). In addition, based on qualitative analysis, higher baseline BP, orthostatic hypertension, impaired baroreflex sensitivity, and several biomarkers are also reported to be associated with significant BP reduction after RDN. CONCLUSIONS: In patients with hypertension treated with the RDN, higher heart rate, and lower pulse wave velocity were associated with significant BP reduction after RDN. Other factors, including higher baseline BP, hypertensive patients with orthostatic hypertension, BP variability, impaired cardiac baroreflex sensitivity, and some biomarkers are also reported to be associated with a better BP response to RDN.

Pyruvate dehydrogenase complex E1 subunit α crotonylation modulates cocaine-associated memory through hippocampal neuron activation.

Neuronal activation is required for the formation of drug-associated memory, which is critical for the development, persistence, and relapse of drug addiction. Nevertheless, the metabolic mechanisms underlying energy production for neuronal activation remain poorly understood. In the study, a large-scale proteomics analysis of lysine crotonylation (Kcr), a type of protein posttranslational modification (PTM), reveals that cocaine promoted protein Kcr in the hippocampal dorsal dentate gyrus (dDG). We find that Kcr is predominantly discovered in a few enzymes critical for mitochondrial energy metabolism; in particular, pyruvate dehydrogenase (PDH) complex E1 subunit α (PDHA1) is crotonylated at the lysine 39 (K39) residue through P300 catalysis. Crotonylated PDHA1 promotes pyruvate metabolism by activating PDH to increase ATP production, thus providing energy for hippocampal neuronal activation and promoting cocaine-associated memory recall. Our findings identify Kcr of PDHA1 as a PTM that promotes pyruvate metabolism to enhance neuronal activity for cocaine-associated memory.

Effect of acupuncture on post-stroke dysphagia: a randomized controlled trial.

Introduction: Post-stroke dysphagia (PSD) is associated with various complications that increase morbidity and mortality rates. Acupuncture has been used extensively in China to treat these complications; however, its therapeutic efficacy remains uncertain. We therefore aimed to study the clinical effects of acupuncture on PSD. Methods: Patients (n = 101) were randomly divided into acupuncture (n = 50) and rehabilitation training control (n = 51) groups based on the treatment used. Both groups were treated once daily, 6 days a week, for a total of 4 weeks. Pulse oxygen saturation (SpO2) and standardized swallowing assessment (SSA) were performed before the intervention, 2 weeks into treatment, after the intervention (4 weeks post-intervention), and at a 6-month follow-up (28 weeks). The levels of hemoglobin (Hb) and albumin (ALB), and 5-hydroxytryptamine (5-HT) and dopamine (DA) were measured before the intervention, 2 weeks into treatment, and after the intervention (4 weeks), as nutrition and swallowing function indices, respectively. Results: Following the intervention, significant differences were observed between the acupuncture and control groups. The acupuncture group exhibited considerably superior enhancements in SpO2 and SSA scores at 4 weeks (p < 0.001). Moreover, this group demonstrated significantly greater improvements in Hb, ALB, 5-HT, and DA values 4 weeks post-treatment (p < 0.001). However, sex-based differences were not observed (P > 0.005). Conclusion: Acupuncture treatment can improve the swallowing function and nutritional status of patients with PSD, and increase the levels of 5-HT and DA. These findings strongly support the efficacy of acupuncture as a therapeutic intervention in patients with PSD.Clinical trial registration: identifier, ChiCTR2100052201. (https://www.chictr.org.cn/).

Effect of human epididymis protein 4 on hyperoxia-induced bronchial dysplasia in newborn rats.

OBJECTIVE: The study aimed to elucidate the role and the underlying mechanism of human epididymis protein 4 (HE4) in the pathogenesis of hyperoxia-induced bronchial dysplasia in newborn rats. METHODS: Forty neonatal Sprague-Dawley (SD) rats were separated into two groups: a normal control group (20.8% oxygen concentration) and a hyperoxia-induced group (85% oxygen concentration). Three time intervals of 24 h, 3 days and 7 days were chosen for each group. Haematoxylin-eosin staining was used to identify the pathological alterations in the lung tissue of the SD rats. Enzyme-linked immunosorbent assay was used to evaluate plasma protein levels. Real-time reverse transcription polymerase chain reaction was used to determine messenger RNA (mRNA) expression. RESULTS: In newborn SD rats, hyperoxia intervention within 7 days may result in acute lung damage. In the plasma and tissue of newborn SD rats, hyperoxia induction may raise levels of HE4, matrix metalloproteinases (MMP) 9 and tissue inhibitors of metalloproteinases (TIMP) 1. We discovered that the HE4 protein activates the phosphorylation of extracellular regulated protein kinases (ERK) and p65, activates the downstream MMP9 signalling pathway, inhibits MMP9 mRNA expression, inhibits protein activity, reduces type I collagen degradation, increases collagen secretion and promotes matrix remodelling and fibrosis in neonatal rat primary alveolar type II epithelial cells by overexpressing and silencing the HE4 gene. CONCLUSION: Through the ERK, MMP9 and TIMP1 signalling pathways, HE4 mediates the pathophysiological process of hyperoxia-induced lung damage in rats. Lung damage and lung basal remodelling are mediated by HE4 overexpression.

U-Shaped Relationship Between Fibrinogen Level and 10-year Mortality in Patients With Acute Coronary Syndrome: Prospective Cohort Study.

This study demonstrated that fibrinogen is an independent risk factor for 10-year mortality in patients with acute coronary syndrome (ACS), with a U-shaped nonlinear relationship observed between the two. These findings underscore the importance of monitoring fibrinogen levels and the consideration of long-term anti-inflammatory treatment in the clinical management of patients with ACS.

Heterogenous Gene Expression of Bicellular and Tricellular Tight Junction-Sealing Components in the Human Intestinal Tract.

A major site for the absorption of orally administered drugs is the intestinal tract, where the mucosal epithelium functions as a barrier separating the inside body from the outer environment. The intercellular spaces between adjacent epithelial cells are sealed by bicellular and tricellular tight junctions (TJs). Although one strategy for enhancing intestinal drug absorption is to modulate these TJs, comprehensive gene (mRNA) expression analysis of the TJs components has never been fully carried out in humans. In this study, we used human biopsy samples of normal-appearing mucosa showing no endoscopically visible inflammation collected from the duodenum, jejunum, ileum, colon, and rectum to examine the mRNA expression profiles of TJ components, including occludin and tricellulin and members of the claudin family, zonula occludens family, junctional adhesion molecule (JAM) family, and angulin family. Levels of claudin-3, -4, -7, -8, and -23 expression became more elevated in each segment along the intestinal tract from the upper segments to the lower segments, as did levels of angulin-1 and -2 expression. In contrast, expression of claudin-2 and -15 was decreased in the large intestine compared to the small intestine. Levels of occludin, tricellulin, and JAM-B and -C expression were unchanged throughout the intestine. Considering their segment specificity, claudin-8, claudin-15, and angulin-2 appear to be targets for the development of permeation enhancers in the rectum, small intestine, and large intestine, respectively. These data on heterogenous expression profiles of intestinal TJ components will be useful for the development of safe and efficient intestinal permeation enhancers.

Mining flotation reagents: Quantitative and robust analysis of metal-xanthate complexes in water.

Xanthates, common mining flotation reagents, strongly bind thiophilic metals such as copper (Cu), lead (Pb), cadmium (Cd), and zinc (Zn) and consequentially change their bioavailability and mobility upon their discharge into the environment. However, accurate quantification of the metal-xanthate complexes has remained elusive. This study develops a novel and robust method that realizes the accurate quantification of the metal-xanthate complexes resulted from single and multiple reactions of three typical xanthates (ethyl, isopropyl, and butyl xanthates) and four thiophilic metals (Cu, Pb, Cd, and Zn) in water samples. This method uses sulfur (S2-) dissociation, followed by tandem solid phase extraction of C18 + PWAX and subsequent LC-MS/MS analysis. It has a wide linearity range (1-1000 µg/L, R2 ≥ 0.995), low method detection limits (0.002-0.036 µg/L), and good recoveries (70.6-107.0 %) at 0.01-10 mg/L of xanthates. Applications of this method showed ubiquitous occurrence of the metal-xanthate complexes as the primary species in flotation wastewaters, which the concentrations were 4.6-28.9-fold higher than those previously determined. It is the first quantitative method established for the analysis of metal-xanthate complexes in water samples, which is of great importance to comprehensively understand the fate and risks of xanthates in the environment.

IPAD-DB: a manually curated database for experimentally verified inhibitors of proteins associated with Alzheimer's disease.

Alzheimer's disease (AD) is a universal neurodegenerative disease with the feature of progressive dementia. Currently, there are only seven Food and Drug Administration-approved drugs for the treatment of AD, which merely offer temporary relief from symptom deterioration without reversing the underlying disease process. The identification of inhibitors capable of interacting with proteins associated with AD plays a pivotal role in the development of effective therapeutic interventions. However, a vast number of such inhibitors are dispersed throughout numerous published articles, rendering it inconvenient for researchers to explore potential drug candidates for AD. In light of this, we have manually compiled inhibitors targeting proteins associated with AD and constructed a comprehensive database known as IPAD-DB (Inhibitors of Proteins associated with Alzheimer's Disease Database). The curated inhibitors within this database encompass a diverse range of compounds, including natural compounds, synthetic compounds, drugs, natural extracts and nano-inhibitors. To date, the database has compiled >4800 entries, each representing a correspondent relationship between an inhibitor and its target protein. IPAD-DB offers a user-friendly interface that facilitates browsing, searching and downloading of its records. We firmly believe that IPAD-DB represents a valuable resource for screening potential AD drug candidates and investigating the underlying mechanisms of this debilitating disease. Access to IPAD-DB is freely available at http://www.lamee.cn/ipad-db/ and is compatible with all major web browsers. Database URL: http://www.lamee.cn/ipad-db/.

Incidence, Predictors, and Outcomes of Paravalvular Regurgitation After TAVR in Sievers Type 1 Bicuspid Aortic Valves.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic valve (BAV) stenosis is technically challenging and is burdened by an increased risk of paravalvular regurgitation (PVR). OBJECTIVES: The aim of this study was to identify the incidence, predictors, and clinical outcomes of PVR after TAVR in Sievers type 1 BAV stenosis. METHODS: Consecutive patients with Sievers type 1 BAV stenosis undergoing TAVR with current-generation transcatheter heart valves (THVs) in 24 international centers were enrolled. PVR was graded as none/trace, mild, moderate, and severe according to echocardiographic criteria. The endpoint of major adverse events (MAEs), defined as a composite of all-cause death, stroke, or hospitalization for heart failure, was assessed at the last available follow-up. RESULTS: A total of 946 patients were enrolled. PVR occurred in 423 patients (44.7%)-mild, moderate, and severe in 387 (40.9%), 32 (3.4%), and 4 (0.4%) patients, respectively. Independent predictors of moderate or severe PVR were a larger virtual raphe ring perimeter (adjusted OR: 1.07; 95% CI: 1.02-1.13), severe annular or left ventricular outflow tract calcification (adjusted OR: 5.21; 95% CI: 1.45-18.77), a self-expanding valve (adjusted OR: 9.01; 95% CI: 2.09-38.86), and intentional supra-annular THV positioning (adjusted OR: 3.31; 95% CI: 1.04-10.54). At a median follow-up of 1.3 years (Q1-Q3: 0.5-2.4 years), moderate or severe PVR was associated with an increased risk of MAEs (adjusted HR: 2.52; 95% CI: 1.24-5.09). CONCLUSIONS: After TAVR with current-generation THVs in Sievers type 1 BAV stenosis, moderate or severe PVR occurred in about 4% of cases and was associated with an increased risk of MAEs during follow-up.