Chemical tools to define and manipulate interferon-inducible Ubl protease USP18.

Ubiquitin-specific protease 18 (USP18) is a multifunctional cysteine protease primarily responsible for deconjugating interferon-inducible ubiquitin-like (Ubl) modifier ISG15 from protein substrates. Here, we report the design and synthesis of activity-based probes (ABPs) capable of selectively detecting USP18 activity over other ISG15 cross-reactive deubiquitinases (DUBs) by incorporating unnatural amino acids into the C-terminal tail of ISG15. Combining with a ubiquitin-based DUB ABP, the selective USP18 ABP is employed in a chemoproteomic screening platform to identify and assess inhibitors of DUBs including USP18. We further demonstrate that USP18 ABPs can be utilized to profile differential activities of USP18 in lung cancer cell lines, providing a strategy that will help define the activity-related landscape of USP18 in different disease states and unravel important (de)ISGylation-dependent biological processes.

Discovery of a Tunable Heterocyclic Electrophile 4-Chloro-pyrazolopyridine That Defines a Unique Subset of Ligandable Cysteines.

Electrophilic small molecules with novel reactivity are powerful tools that enable activity-based protein profiling and covalent inhibitor discovery. Here, we report a reactive heterocyclic scaffold, 4-chloro-pyrazolopyridine (CPzP) for selective modification of proteins via a nucleophilic aromatic substitution (SNAr) mechanism. Chemoproteomic profiling reveals that CPzPs engage cysteines within functionally diverse protein sites including ribosomal protein S5 (RPS5), inosine monophosphate dehydrogenase 2 (IMPDH2), and heat shock protein 60 (HSP60). Through the optimization of appended recognition elements, we demonstrate the utility of CPzP for covalent inhibition of prolyl endopeptidase (PREP) by targeting a noncatalytic active-site cysteine. This study suggests that the proteome reactivity of CPzPs can be modulated by both electronic and steric features of the ring system, providing a new tunable electrophile for applications in chemoproteomics and covalent inhibitor design.

Cardiovascular outcomes in solid organ transplant recipients undergoing cardiac surgery: A matched pair analysis.

INTRODUCTION: This study aimed to compare postoperative outcomes after cardiac surgery in solid-organ transplant recipients and nontransplant patients. METHODS: We performed a retrospective analysis of 78 consecutive transplant recipients who underwent cardiac surgery at Asan Medical Center between 2000 and 2022 and were matched with 312 nontransplant patients who underwent cardiac surgery at a 1:4 ratio. The outcomes included 30-day mortality, all-cause death, cardiac death, readmission, and cardiac readmission. RESULTS: There was no significant difference in baseline characteristics between the two groups. The most common type of cardiac surgery performed in solid organ transplant recipients was isolated valve surgery, followed by isolated CABG. The 30-day mortality was not significantly different between transplant recipients and nontransplant patients (3.9% vs. 3.5%; P > .99). Solid organ transplant recipients showed a higher all-cause mortality compared to nontransplant patients (29.1% vs. 14.3% at 5 years; P = .001); however, there was no significant difference in cardiac death between the two groups (2.6% vs. 3.2% at 5 years; P = .80). In addition, the readmission and cardiac readmission rates showed comparable findings to that of mortality. CONCLUSION: Cardiac surgery can be performed safely in solid organ transplant recipients, with postoperative cardiovascular outcomes comparable to those observed in nontransplant patients.

Mechanical versus Bioprosthetic Aortic Valve Replacement in Patients Aged 50 to 70 Years.

Background: This study compared the outcomes of surgical aortic valve replacement (AVR) in patients aged 50 to 70 years based on the type of prosthetic valve used. Methods: We compared patients who underwent mechanical AVR to those who underwent bioprosthetic AVR at our institution between January 2000 and March 2019. Competing risk analysis and the inverse probability of treatment weighting (IPTW) method based on propensity score were employed for comparisons. Results: A total of 1,580 patients (984 patients with mechanical AVR; 596 patients with bioprosthetic AVR) were enrolled. There was no significant difference in early mortality between the mechanical AVR and bioprosthetic AVR groups (0.9% vs. 1.7%, p=0.177). After IPTW adjustment, the risk of all-cause mortality was significantly higher in the bioprosthetic AVR group than in the mechanical AVR group (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.07-1.80; p=0.014). Competing risk analysis revealed lower risks of stroke (sub-distributional hazard ratio [sHR], 0.44; 95% CI, 0.28-0.67; p<0.001) and anticoagulation-related bleeding (sHR, 0.35; 95% CI, 0.23-0.53; p<0.001) in the bioprosthetic AVR group. Conversely, the risk of aortic valve (AV) reintervention was higher in the bioprosthetic AVR group (sHR, 6.14; 95% CI, 3.17-11.93; p<0.001). Conclusion: Among patients aged 50 to 70 years who underwent surgical AVR, those receiving mechanical valves showed better survival than those with bioprosthetic valves. The mechanical AVR group exhibited a higher risk of stroke and anticoagulation-related bleeding, while the bioprosthetic AVR group showed a higher risk of AV reintervention.

SP-8356 inhibits acute lung injury by suppressing inflammatory cytokine production and immune cell infiltration.

This study investigated the anti-inflammatory and protective properties of SP-8356, a synthetic derivative of (1S)-(-)-verbenone, in a mouse model of LPS-induced acute lung injury (ALI). By targeting intracellular signaling pathways and inflammatory responses, SP-8356 demonstrated a potent ability to attenuate deleterious effects of proinflammatory stimuli. Specifically, SP-8356 effectively inhibited the activation of crucial signaling molecules such as NF-κB and Akt, and subsequently dampened the expression of inflammatory cytokines in various lung cellular components. Intervention with SP-8356 treatment also preserved the structural integrity of the epithelial and endothelial barriers. By reducing immune cell infiltration into inflamed lung tissue, SP-8356 exerted a broad protective effect against ALI. These findings position SP-8356 as a promising therapeutic candidate for pulmonary inflammatory diseases that cause ALI.

Recent Outcomes of Surgical Redo Aortic Valve Replacement in Prosthetic Valve Failure.

BACKGROUND: As redo surgical aortic valve replacement (AVR) is relatively high risk, valve-in-valve transcatheter AVR has emerged as an alternative for failed prostheses. However, the majority of studies are outdated. This study assessed the current clinical outcomes of redo AVR. METHODS AND RESULTS: This study enrolled 324 patients who underwent redo AVR due to prosthetic valve failure from 2010 to 2021 in four tertiary centers. The primary outcome was operative mortality. The secondary outcomes were overall survival, cardiac death, and aortic valve-related events. Logistic regression analysis, clustered Cox proportional hazards models, and competing risk analysis were used to evaluate the independent risk factors. Redo AVR was performed in 242 patients without endocarditis and 82 patients with endocarditis. Overall operative mortality was 4.6% (15 deaths). Excluding patients with endocarditis, the operative mortality of redo AVR decreased to 2.5%. Multivariate analyses demonstrated that endocarditis (hazard ratio [HR]: 3.990, p = 0.014), longer cardiopulmonary bypass time (HR: 1.006, p = 0.037), and lower left ventricular ejection fraction (LVEF) (HR: 0.956, p = 0.034) were risk factors of operative mortality. Endocarditis and lower LVEF were independent predictors of overall survival. CONCLUSION: The relatively high risk of redo AVR was due to reoperation for prosthetic valve endocarditis. The outcomes of redo AVR for nonendocarditis are excellent. Our findings suggest that patients without endocarditis, especially with acceptable LVEF, can be treated safely with redo AVR.

Surgical Outcomes of Centrifugal Continuous-Flow Implantable Left Ventricular Assist Devices: Heartmate 3 versus Heartware Ventricular Assist Device.

Background: Left ventricular assist devices (LVADs) are widely employed as a therapeutic option for end-stage heart failure. We evaluated the outcomes associated with centrifugal-flow LVAD implantation, comparing 2 device models: the Heartmate 3 (HM3) and the Heartware Ventricular Assist Device (HVAD). Methods: Data were collected from patients who underwent LVAD implantation between June 1, 2015 and December 31, 2022. We analyzed overall survival, first rehospitalization, and early, late, and LVAD-related complications. Results: In total, 74 patients underwent LVAD implantation, with 42 receiving the HM3 and 32 the HVAD. A mild Interagency Registry for Mechanically Assisted Circulatory Support score was more common among HM3 than HVAD recipients (p=0.006), and patients receiving the HM3 exhibited lower rates of preoperative ventilator use (p=0.010) and extracorporeal membrane oxygenation (p=0.039). The overall early mortality rate was 5.4% (4 of 74 patients), with no significant difference between groups. Regarding early right ventricular (RV) failure, HM3 implantation was associated with a lower rate (13 of 42 [31.0%]) than HVAD implantation (18 of 32 [56.2%], p=0.051). The median rehospitalization-free period was longer for HM3 recipients (16.9 months) than HVAD recipients (5.3 months, p=0.013). Furthermore, HM3 recipients displayed a lower incidence of late hemorrhagic stroke (p=0.016). In the multivariable analysis, preoperative use of continuous renal replacement therapy (odds ratio, 22.31; p=0.002) was the only significant predictor of postoperative RV failure. Conclusion: The LVAD models (HM3 and HVAD) demonstrated comparable overall survival rates. However, the HM3 was associated with a lower risk of late hemorrhagic stroke.

Prognostic impact of the E/e' ratio in patients with chronic severe aortic regurgitation undergoing aortic valve replacement.

OBJECTIVES: The study objective was to evaluate the clinical implication of left ventricular diastolic dysfunction in patients with chronic severe aortic regurgitation undergoing aortic valve replacement. METHODS: We reviewed the medical records of 323 patients (age, 56.3 ± 14.1 years; 111 female) who underwent aortic valve replacement for chronic severe aortic regurgitation between 2005 and 2019. Left ventricular diastolic dysfunction was assessed by the ratio of peak left ventricular inflow velocity over mitral annular velocity (E/e'). The study end point was the composite of death and heart failure requiring hospital admission. RESULTS: The E/e' ratio was significantly correlated with age, left atrial dimension, left ventricular end-diastolic volume, mitral regurgitation grade, and tricuspid regurgitation grade (all P < .001). During follow-up (1748.3 patient-years), death and heart failure occurred in 36 patients (2.06/patient-year) and 9 patients (0.53/patient-year), respectively. In multivariable analysis, E/e' ratio (per 5 increment, hazard ratio, 1.32; 95% confidence interval, 1.02-1.71; P = .03), age (hazard ratio, 1.06; 95% confidence interval, 1.03-1.10; P < .001), and left ventricular ejection fraction (hazard ratio, 0.94; 95% confidence interval, 0.90-0.98; P = .002) were independent predictors of death and heart failure. The 5-year heart failure-free survival was 94.9% ± 1.7% in patients with E/e' less than 15% and 84.2% ± 4.2% in patients with E/e' 15 or greater (P < .001). CONCLUSIONS: The E/e' ratio was significantly associated with adverse outcomes in patients with chronic severe aortic regurgitation undergoing aortic valve replacement and may be useful as a prognostic marker in such patients.

Synthesis of 9-Cinnamyl-9H-purine Derivatives as Novel TLR4/MyD88/NF-κB Pathway Inhibitors for Anti-inflammatory Effects.

The novel 9-cinnamyl-9H-purine skeleton, inspired by resveratrol and curcumin, was developed to avoid a pan-assay interference compound (PAINS) related to invalid metabolic pancreas activity (IMPS). It replaced the phenol group with purine analogues, the building blocks of DNA and RNA. Alterations to the hydroxyl group in the cinnamyl group, such as H, Me, or F substitutions, were made to impede its oxidation to a PAINS-associated quinone. Among the compounds tested, 5e significantly inhibited nitric oxide production in LPS-induced macrophages (IC50: 6.4 vs 26.4 µM for resveratrol). 5e also reduced pro-inflammatory cytokine levels (IL-6, TNF-α, IL-1ß) and lowered iNOS and COX-2 protein levels. Mechanistically, 5e disrupted the TLR4-MyD88 protein interaction, leading to the suppression of the NF-κB signaling pathway suppression. In an atopic dermatitis mouse model, 5e reduced ear edema and inflammation. These findings indicate that the novel 9-cinnamyl-9H-purine skeleton provides therapeutic insight into treating various human diseases by regulating inflammation.

Neurokinin-2 receptor negatively modulates substance P responses by forming complex with Neurokinin-1 receptor.

BACKGROUND: Tachykinins and their cognate receptors, neurokinin receptors (NKs) including NK1, NK2, and NK3 play vital roles in regulating various physiological processes including neurotransmission, nociception, inflammation, smooth muscle contractility, and stimulation of endocrine and exocrine gland secretion. Their abnormal expression has been reported to be associated with neurological disorders, inflammation, and cancer. Even though NKs are expressed in the same cells with their expression being inversely correlated in some conditions, there is no direct evidence to prove their interaction. Understanding the functional crosstalk between NKs in mediated downstream signaling and cellular responses may elucidate the roles of each receptor in pathophysiology. RESULTS: In this study, we showed that NKs were co-expressed in some cells. However, different from NK3, which only forms homodimerization, we demonstrated a direct interaction between NK1 and NK2 at the protein level using co-immunoprecipitation and NanoBiT-based protein interaction analysis. Through heterodimerization, NK2 downregulated substance P-stimulated NK1 signals, such as intracellular Ca2+ mobilization and ERK phosphorylation, by enhancing ß-arrestin recruitment, even at the ligand concentration that could not activate NK2 itself or in the presence of NK1 specific antagonist, aprepitant. In A549 cells with receptors deleted and reconstituted, NK2 exerted a negative effect on substance P/NK1-mediated cell migration. CONCLUSION: Our study has provided the first direct evidence of an interaction between NK1 and NK2, which highlights the functional relevance of their heterodimerization in cellular responses. Our findings demonstrated that through dimerization, NK2 exerts negative effects on downstream signaling and cellular response mediated by NK1. Moreover, this study has significant implications for understanding the complexity of GPCR dimerization and its effect on downstream signaling and cellular responses. Given the important roles of tachykinins and NKs in pathophysiology, these insights may provide clues for developing NKs-targeting drugs.

Defect-Passivated Photosensor Based on Cesium Lead Bromide (CsPbBr3) Perovskite Quantum Dots for Microbial Detection.

A defect-passivated photosensor based on cesium lead bromide (CsPbBr3) perovskite quantum dots (QD) was fabricated using parylene films, and the photosensor was applied for the microbial detection. The CsPbBr3 perovskite QDs were synthesized to be homogeneous in size under thermodynamic control, and the perovskite QD-based photosensor was fabricated using MoS2 flakes as the electron transfer layer. In this work, a parylene film with functional groups was deposited on a photosensor for physical protection (waterproof) and defect (halide vacancy) passivation of the perovskite QD. As the first effect of the parylene film, the physical protection of the perovskite QD from water was estimated by comparing the photosensor performance after incubation in water. As the second effect of the parylene, the interaction between the functional groups of the parylene film and the halide vacancies of the perovskite QDs was investigated through the bandgap, crystal structure, and trap-state density analysis. Additionally, density functional theory analysis on Mulliken charges, lattice parameters, and Gibbs free energy demonstrated the effect of the defect passivation by parylene films. Finally, the parylene-passivated QD-based photosensor was applied to the detection of two kinds of food-poisoning and gastroduodenal disease bacteria (Listeria monocytogenes and Helicobacter pylori).

Bovine pericardial versus porcine bioprosthetic aortic valves: A nationwide population-based cohort study in Korea.

OBJECTIVE: To compare the clinical outcomes of aortic valve replacement (AVR) using bovine pericardial and porcine bioprostheses, utilizing a nationwide administrative claims database. METHODS: Adult patients (age ≥40 years) who underwent bioprosthetic AVR, without other valve replacements, between 2003 and 2018 were identified from the Korean National Health Insurance Service database. The outcomes of interest were all-cause mortality, cardiac mortality, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. Baseline adjustment was performed using propensity score matching. Time-related outcomes were evaluated using a competing risk analysis, with death as a competing risk. RESULTS: Among the 7714 patients who underwent bioprosthetic AVR, 5621 (72.9%) received bovine pericardial prostheses and 2093 (27.1%) received porcine bioprostheses. After matching, 1937 pairs were included in the final analysis. During follow-up (median, 4.49 years; interquartile range, 2.83-8.20 years), the use of porcine bioprostheses was associated with a higher risk of aortic valve reoperation (adjusted hazard ratio [HR], 1.87; 95% confidence interval [CI], 1.16 to 3.01); however, no significant differences were observed in cumulative incidences of all-cause mortality, cardiac mortality, thromboembolism, or major bleeding. Subgroup analyses revealed that the use of bovine valves was associated with improved survival in patients with diabetes mellitus, whereas in patients undergoing dialysis, porcine valves exhibited better survival than bovine valves. CONCLUSIONS: In this large nationwide cohort study of patients undergoing bioprosthetic aortic valve replacement, the use of porcine prostheses was significantly associated with an increased risk of reoperation compared with the use of bovine prostheses, supporting previous findings.

Discovery of Chemical Scaffolds as Lysophosphatidic Acid Receptor 1 Antagonists: Virtual Screening, In Vitro Validation, and Molecular Dynamics Analysis.

Lysophosphatidic acid receptor 1 (LPAR1) is an emerging therapeutic target for numerous human diseases including fibrosis. However, the limited number of available core structures of LPAR1 antagonists has prompted the need for novel chemical templates. In this study, we conducted a high-throughput virtual screening to discover potential new scaffolds. We tested three existing crystal structures alongside an AlphaFold model to evaluate their suitability in structure-based virtual screening, finding that the crystal structures show superior performance compared with the predictive model. Furthermore, we also found that enhancing the precision in the screening process did not necessarily improve the enrichment of hits. From the screening campaign, we identified five structures that were validated using an LPAR1-dependent calcium flux assay. To gain a deeper insight into the protein-ligand interaction, we extensively analyzed the binding modes of these compounds using in silico techniques, laying the groundwork for the discovery of novel LPAR1 antagonists.

The result of prospective evaluation of 3-dimensional printing-aided extensive thoracoabdominal aorta repair.

Objectives: Paraplegia is a distressing complication after open thoracoabdominal aortic aneurysm (TAAA) repair, and revascularization of T8-L2-level segmental arteries is considered pivotal to prevent paraplegia. We employed 3-dimensional (3D) printing to efficiently revascularize segmental/visceral arteries and prospectively evaluated its safety and efficacy. Methods: From January 1, 2020, to June 30, 2022, we prospectively enrolled patients of extent I, II, or III TAAA repair. Guidance models were 3D-printed based on preoperative computed tomography, and multibranched aortic grafts were manually constructed upon this model before surgery. The composite outcome of operative mortality, permanent stroke, and permanent spinal cord deficit (SCD) was compared with the historical control group (n = 77, in 2015-2020), subjected to similar TAAA repair without 3D printing. Results: A total of 38 patients (58.6 ± 13.2 years) underwent open TAAA repair with the aid of 3D printing. Extent I, II, and III repairs were performed in 14 (36.8%), 17 (44.7%), and 7 (18.4%), respectively. Concomitant arch repair and bi-iliac reconstruction were performed in 7 (18.4%) and 6 patients (15.8%), respectively. Mean pump time was 107.7 ± 55.5 minutes. Operative mortality, permanent stroke, and permanent SCD each occurred in 1 patient (2.6%), and the incidence of the composite outcome was 7.9% (3/38). In the control group, mean pump time was 166.0 ± 83.9 minutes, significantly longer than the 3D-printing group (P < .001), and operative mortality, permanent stroke, permanent SCD, and the composite outcome occurred in 7 (9.1%), 9 (11.7%), 8 (10.4%), and 19 (24.7%), respectively. Conclusions: Open repairs of extensive TAAA with 3D printing showed favorable safety and efficacy, which need further validation by larger studies.

Effects of hole transporting PEDOT:PSS on the photoemission of upconverted hot electron in Mn-doped CdS/ZnS quantum dots.

In this work, we investigated the effect of hole transporting poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) interfacing with Mn-doped CdS/ZnS quantum dots (QDs) deposited on an indium tin oxide (ITO) substrate on the photoemission of upconverted hot electrons under weak continuous wave photoexcitation in a vacuum. Among the various factors that can influence the photoemission of the upconverted hot electrons, we studied the role of PEDOT:PSS in facilitating the hole transfer from QDs and altering the energy of photoemitted hot electrons. Compared to hot electrons emitted from QDs deposited directly on the ITO substrate, the addition of the PEDOT:PSS layer between the QD and ITO layers increased the energy of the photoemitted hot electrons. The increased energy of the photoemitted hot electrons is attributed in part to the reduced steady-state positive charge on the QDs under continuous photoexcitation, which reduces the energy required to eject the electron from the conduction band.

The N-terminus of CXCR4 splice variants determines expression and functional properties.

C-X-C motif chemokine ligand 12(CXCL12) is an essential chemokine for organ development and homeostasis in multiple tissues. Its receptor, C-X-C chemokine receptor type 4(CXCR4), is expressed on the surface of target cells. The chemokine and receptor are expressed almost ubiquitously in human tissues and cells throughout life, and abnormal expression of CXCL12 and CXCR4 is observed in pathological conditions, such as inflammation and cancer. CXCR4 is reportedly translated into five splicing variants of different lengths, which each have different amino acids in the N-terminus. As the N-terminus is the first recognition site for chemokines, CXCR4 variants may respond differently to CXCL12. Despite these differences, the molecular and functional properties of CXCR4 variants have not been thoroughly described or compared. Here, we explored the expression of CXCR4 variants in cell lines and analyzed their roles in cellular responses using biochemical approaches. RT-PCR revealed that most cell lines express more than one CXCR4 variant. When expressed in HEK293 cells, the CXCR4 variants differed in protein expression efficiency and cell surface localization. Although variant 2 demonstrated the strongest expression and cell surface localization, variants 1, 3, and 5 also mediated chemokine signaling and induced cellular responses. Our results demonstrate that the N-terminal sequences of each CXCR4 variant determine the expression of the receptor and affect ligand recognition. Functional analyses revealed that CXCR4 variants may also affect each other or interact during CXCL12-stimulated cellular responses. Altogether, our results suggest that CXCR4 variants may have distinct functional roles that warrant additional investigation and could contribute to future development of novel drug interventions.

Isolation of a polyethylene-degrading bacterium, Acinetobacter guillouiae, using a novel screening method based on a redox indicator.

Plastic, a polymer synthesized from petrochemicals, is used worldwide. However, natural degradation of plastic is difficult, causing environmental pollution, with microplastics posing a serious threat to human health. In this study, we aimed to use a new screening method based on the oxidation-reduction indicator, 2,6-dichlorophenolindophenol, to isolate a polyethylene-degrading bacterium, Acinetobacter guillouiae, from insect larvae. Plastic-degrading strains are identified by the color change in the redox indicator from blue to colorless as plastic metabolism occurs. Polyethylene biodegradation by A. guillouiae was verified through weight loss, surface erosion, physiological evidence, and chemical changes on the plastic surface. In addition, we analyzed the characteristics of hydrocarbon metabolism in polyethylene-degrading bacteria. Results suggested that alkane hydroxylation and alcohol dehydrogenation were key steps in polyethylene degradation. This novel screening method will pave the way for high-throughput screening of polyethylene-degrading microorganisms and extending its application to other types of plastics may potentially address plastic pollution.

Covalent Inhibition by a Natural Product-Inspired Latent Electrophile.

Strategies to target specific protein cysteines are critical to covalent probe and drug discovery. 3-Bromo-4,5-dihydroisoxazole (BDHI) is a natural product-inspired, synthetically accessible electrophilic moiety that has previously been shown to react with nucleophilic cysteines in the active site of purified enzymes. Here, we define the global cysteine reactivity and selectivity of a set of BDHI-functionalized chemical fragments using competitive chemoproteomic profiling methods. Our study demonstrates that BDHIs capably engage reactive cysteine residues in the human proteome and the selectivity landscape of cysteines liganded by BDHI is distinct from that of haloacetamide electrophiles. Given its tempered reactivity, BDHIs showed restricted, selective engagement with proteins driven by interactions between a tunable binding element and the complementary protein sites. We validate that BDHI forms covalent conjugates with glutathione S-transferase Pi (GSTP1) and peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), emerging anticancer targets. BDHI electrophile was further exploited in Bruton's tyrosine kinase (BTK) inhibitor design using a single-step late-stage installation of the warhead onto acrylamide-containing compounds. Together, this study expands the spectrum of optimizable chemical tools for covalent ligand discovery and highlights the utility of 3-bromo-4,5-dihydroisoxazole as a cysteine-reactive electrophile.

Bovine pericardial versus porcine bioprosthetic mitral valves: results from a Korean Nationwide Cohort Study.

OBJECTIVES: Comparisons of long-term clinical outcomes of mitral valve replacement (MVR) between bovine pericardial and porcine bioprostheses are conflicting, with limited research in large-scale real-world clinical settings. This study examined clinical outcomes in MVR according to bioprosthesis type using a national administrative claims database. METHODS: This study included adult patients undergoing bioprosthetic MVR between 2003 and 2018 using administrative health care data from the Korean National Health Insurance Service database. Propensity score matching with competing risk analysis was used to compare the clinical outcomes according to the type of bioprosthesis. The end points were death, cardiac death, and valve-related events, including the incidence of reoperation, endocarditis, systemic thromboembolism, and major bleeding. RESULTS: A total of 3151 patients underwent bioprosthetic MVR with bovine pericardial (n = 1628, 51.7%) or porcine (n = 1523, 48.3%) bioprostheses. After matching, 1170 pairs were included in the final analysis. During follow-up (median 4.49 years, interquartile range 1.87 -8.75 years), death occurred in 1178 patients (6.8%/patient-year), comprising 730 (4.3%/patient-year) cardiac death. No significant differences were noted between the bovine and porcine groups in the cumulative incidences of death from any cause [adjusted hazard ratio (aHR), 1.00; 95% confidence interval (CI), 0.87-1.14], cardiac mortality (aHR, 0.96; 95% CI, 0.81-1.14), or reoperation (aHR, 1.01; 95% CI, 0.72-1.41). CONCLUSIONS: This study on a nationwide comparison between bovine and porcine bioprostheses in MVR found no significant differences in clinical outcomes including mortality, and valve-related reoperation.