Stratifying heart failure patients with graph neural network and transformer using Electronic Health Records to optimize drug response prediction.

OBJECTIVES: Heart failure (HF) impacts millions of patients worldwide, yet the variability in treatment responses remains a major challenge for healthcare professionals. The current treatment strategies, largely derived from population based evidence, often fail to consider the unique characteristics of individual patients, resulting in suboptimal outcomes. This study aims to develop computational models that are patient-specific in predicting treatment outcomes, by utilizing a large Electronic Health Records (EHR) database. The goal is to improve drug response predictions by identifying specific HF patient subgroups that are likely to benefit from existing HF medications. MATERIALS AND METHODS: A novel, graph-based model capable of predicting treatment responses, combining Graph Neural Network and Transformer was developed. This method differs from conventional approaches by transforming a patient's EHR data into a graph structure. By defining patient subgroups based on this representation via K-Means Clustering, we were able to enhance the performance of drug response predictions. RESULTS: Leveraging EHR data from 11 627 Mayo Clinic HF patients, our model significantly outperformed traditional models in predicting drug response using NT-proBNP as a HF biomarker across five medication categories (best RMSE of 0.0043). Four distinct patient subgroups were identified with differential characteristics and outcomes, demonstrating superior predictive capabilities over existing HF subtypes (best mean RMSE of 0.0032). DISCUSSION: These results highlight the power of graph-based modeling of EHR in improving HF treatment strategies. The stratification of patients sheds light on particular patient segments that could benefit more significantly from tailored response predictions. CONCLUSIONS: Longitudinal EHR data have the potential to enhance personalized prognostic predictions through the application of graph-based AI techniques.

Occurrence and Distribution of Antibacterial Quaternary Ammonium Compounds in Chinese Estuaries Revealed by Machine Learning-Assisted Mass Spectrometric Analysis.

Antimicrobial resistance (AMR) undermines the United Nations Sustainable Development Goals of good health and well-being. Antibiotics are known to exacerbate AMR, but nonantibiotic antimicrobials, such as quaternary ammonium compounds (QACs), are now emerging as another significant driver of AMR. However, assessing the AMR risks of QACs in complex environmental matrices remains challenging due to the ambiguity in their chemical structures and antibacterial activity. By machine learning prediction and high-resolution mass spectrometric analysis, a list of antibacterial QACs (n = 856) from industrial chemical inventories is compiled, and it leads to the identification of 50 structurally diverse antibacterial QACs in sediments, including traditional hydrocarbon-based compounds and new subclasses that bear additional functional groups, such as choline, ester, betaine, aryl ether, and pyridine. Urban wastewater, aquaculture, and hospital discharges are the main factors influencing QAC distribution patterns in estuarine sediments. Toxic unit calculations and metagenomic analysis revealed that these QACs can influence antibiotic resistance genes (particularly sulfonamide resistance genes) through cross- and coresistances. The potential to influence the AMR is related to their environmental persistence. These results suggest that controlling the source, preventing the co-use of QACs and sulfonamides, and prioritizing control of highly persistent molecules will lead to global stewardship and sustainable use of QACs.

Therapeutic strategies targeting mechanisms of macrophages in diabetic heart disease.

Diabetic heart disease (DHD) is a serious complication in patients with diabetes. Despite numerous studies on the pathogenic mechanisms and therapeutic targets of DHD, effective means of prevention and treatment are still lacking. The pathogenic mechanisms of DHD include cardiac inflammation, insulin resistance, myocardial fibrosis, and oxidative stress. Macrophages, the primary cells of the human innate immune system, contribute significantly to these pathological processes, playing an important role in human disease and health. Therefore, drugs targeting macrophages hold great promise for the treatment of DHD. In this review, we examine how macrophages contribute to the development of DHD and which drugs could potentially be used to target macrophages in the treatment of DHD.

Incidence and Impact of Takotsubo Syndrome in Hospitalized Patients With COVID-19.

BACKGROUND: Takotsubo syndrome has been reported in patients with COVID-19, although minimal data are available. This investigation assessed the incidence and impact of takotsubo syndrome on patients hospitalized with COVID-19. METHODS: A retrospective cohort study was conducted using International Statistical Classification of Diseases, Tenth Revision, codes to identify patients with a primary diagnosis of COVID-19 with or without takotsubo syndrome in the National Inpatient Sample 2020 database. Outcomes between groups were compared after propensity score matching for patient and hospital demographics and comorbidities. RESULTS: A total of 211,448 patients with a primary diagnosis of COVID-19 were identified. Of these, 171 (0.08%) had a secondary diagnosis of takotsubo syndrome. Before matching, patients with COVID-19 and takotsubo syndrome, compared with patients without takotsubo syndrome, were older (68.95 vs 64.26 years; P < .001); more likely to be female (64.3% vs 47.2%; P < .001); and more likely to have anxiety (24.6% vs 12.8%; P < .001), depression (17.5% vs 11.4%; P = .02), and chronic obstructive pulmonary disease (24.6% vs 14.7%; P < .001). The takotsubo syndrome group had worse outcomes than the non-takotsubo syndrome group for death (30.4% vs 11.1%), cardiac arrest (7.6% vs 2.1%), cardiogenic shock (12.9% vs 0.4%), length of hospital stay (10.7 vs 7.5 days), and total charges ($152,685 vs $78,468) (all P < .001). After matching and compared with the non-takotsubo syndrome group (n = 508), the takotsubo syndrome group (n = 170) had a higher incidence of inpatient mortality (30% vs 14%; P < .001), cardiac arrest (7.6% vs 2.8%; P = .009), and cardiogenic shock (12.4% vs 0.4%; P < .001); a longer hospital stay (10.7 vs 7.6 days; P < .001); and higher total charges ($152,943 vs $79,523; P < .001). CONCLUSION: Takotsubo syndrome is a rare but severe in-hospital complication in patients with COVID-19.

Association of Lipoprotein(a) Levels With Myocardial Infarction in Patients With Low-Attenuation Plaque.

BACKGROUND: Lipoprotein(a) (Lp[a]) is associated with an increased risk of myocardial infarction (MI). However, the mechanism underlying this association has yet to be fully elucidated. OBJECTIVES: This multicenter study aimed to investigate whether association between Lp(a) and MI risk is reinforced by the presence of low-attenuation plaque (LAP) identified by coronary computed tomography angiography (CCTA). METHODS: In a derivation cohort, a total of 5,607 patients with stable chest pain suspected of coronary artery disease who underwent CCTA and Lp(a) measurement were prospectively enrolled. In validation cohort, 1,122 patients were retrospectively collected during the same period. High Lp(a) was defined as Lp(a) ≥50 mg/dL. The primary endpoint was a composite of time to fatal or nonfatal MI. Associations were estimated using multivariable Cox proportional hazard models. RESULTS: During a median follow-up of 8.2 years (Q1-Q3: 7.2-9.3 years), the elevated Lp(a) levels were associated with MI risk (adjusted HR [aHR]: 1.91; 95% CI: 1.46-2.49; P < 0.001). There was a significant interaction between Lp(a) and LAP (Pinteraction <0.001) in relation to MI risk. When stratified by the presence or absence of LAP, Lp(a) was associated with MI in patients with LAP (aHR: 3.03; 95% CI: 1.92-4.76; P < 0.001). Mediation analysis revealed that LAP mediated 73.3% (P < 0.001) for the relationship between Lp(a) and MI. The principal findings remained unchanged in the validation cohort. CONCLUSIONS: Elevated Lp(a) augmented the risk of MI during 8 years of follow-up, especially in patients with LAP identified by CCTA. The presence of LAP could reinforce the relationship between Lp(a) and future MI occurrence.

Microstructure and Mechanical Properties of Refill Friction Stir Spot-Welded Joints of 2A12Al and 7B04Al: Effects of Tool Size and Welding Parameters.

To solve problems in dissimilarly light metal joints, refilled friction stir spot welding (RFSSW) is proposed instead of resistance spot welding. However, rotation speed, dwell time, plunge depth, and the diameter of welding tools all have a great influence on joints, which brings great challenges in optimizing welding parameters to ensure their mechanical properties. In this study, the 1.5 mm thick 2A12Al and 2 mm thick 7B04Al lap joints were prepared by Taguchi orthogonal experiment design and RFSSW. The welding tool (shoulder) diameters were 5 mm and 7 mm, respectively. The macro/microstructures of the cross-section, the geometrical characteristics of the effective welding depth (EWD), the stir zone area (SZA), and the stir zone volume (SZV) were characterized. The shear strength and failure mode of the lap joint were analyzed using an optical microscope. It was found that EWD, SZA, and SZV had a good correlation with tensile-shear force. The optimal welding parameters of 5 mm diameter joints are 1500 rpm of rotation speed, 2.5 mm of plunge depth, and 0 s of dwell time, which for 7 mm joints are 1200 rpm, 1.5 mm, and 2 s. The tensile-shear force of 5 mm and 7 mm joints welded with these optical parameters was 4965 N and 5920 N, respectively. At the same time, the 5 mm diameter joints had better strength and strength stability.

Occurrence and Ecological Risk of Alkylamine Triazines in Chinese Estuarine Sediments: An Emerging Class of Persistent, Mobile, and Toxic Substances.

Identifying persistent, mobile, and toxic (PMT) substances from synthetic chemicals is critical for chemical management and ecological risk assessment. Inspired by the triazine analogues (e.g., atrazine and melamine) in the original European Union's list of PMT substances, the occurrence and compositions of alkylamine triazines (AATs) in the estuarine sediments of main rivers along the eastern coast of China were comprehensively explored by an integrated strategy of target, suspect, and nontarget screening analysis. A total of 44 AATs were identified, of which 23 were confirmed by comparison with authentic standards. Among the remaining tentatively identified analogues, 18 were emerging pollutants not previously reported in the environment. Tri- and di-AATs were the dominant analogues, and varied geographic distributions of AATs were apparent in the investigated regions. Toxic unit calculations indicated that there were acute and chronic risks to algae from AATs on a large geographical scale, with the antifouling biocide cybutryne as a key driver. The assessment of physicochemical properties further revealed that more than half of the AATs could be categorized as potential PMT and very persistent and very mobile substances at the screening level. These results highlight that AATs are a class of PMT substances posing high ecological impacts on the aquatic environment and therefore require more attention.

Biobased Inks Based on Cuttlefish Ink and Cellulose Nanofibers for Biodegradable Patterned Soft Actuators.

Soft actuators with stimuli-responsive and reversible deformations have shown great promise in soft robotics. However, some challenges remain in existing actuators, such as the materials involved derived from nonrenewable resources, complex and nonscalable preparation methods, and incapability of complex and programmable deformation. Here, a biobased ink based on cuttlefish ink nanoparticles (CINPs) and cellulose nanofibers (CNFs) was developed, allowing for the preparation of biodegradable patterned actuators by direct ink writing technology. The hybrid CNF/CINP ink displays good rheological properties, allowing it to be accurately printed on a variety of flexible substrates. A bilayer actuator was developed by printing an ink layer on a biodegradable poly(lactic acid) film using extrusion-based 3D printing technology, which exhibits reversible and large bending behavior under the stimuli of humidity and light. Furthermore, programmable and reversible folding and coiling deformations in response to stimuli have been achieved by adjusting the ink patterns. This work offers a fast, scalable, and cost-effective strategy for the development of biodegradable patterned actuators with programmable shape-morphing.

Perfluorobutanoic acid triggers metabolic and transcriptional reprogramming in wheat seedlings.

The environmental risks of fluorinated alternatives are of great concern with the phasing out of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate. Here, multi-omics (i.e., metabolomics and transcriptomics) coupled with physiological and biochemical analyses were employed to investigate the stress responses of wheat seedings (Triticum aestivum L.) to perfluorobutanoic acid (PFBA), one of the short-chain per- and polyfluoroalkyl substances (PFAS) and PFOA alternatives, at environmentally relevant concentrations (0.1-100 ng/g). After 28 days of soil exposure, PFBA boosted the generation of OH and O2- in wheat seedlings, resulting in lipid peroxidation, protein perturbation and impaired photosynthesis. Non-enzymatic antioxidant defense systems (e.g., glutathione, phenolics, and vitamin C) and enzymatic antioxidant copper/zinc superoxide dismutase were strikingly activated (p < 0.05). PFBA-triggered oxidative stress induced metabolic and transcriptional reprogramming, including carbon and nitrogen metabolisms, lipid metabolisms, immune responses, signal transduction processes, and antioxidant defense-related pathways. Down-regulation of genes related to plant-pathogen interaction suggested suppression of the immune-response, offering a novel understanding on the production of reactive oxygen species in plants under the exposure to PFAS. The identified MAPK signaling pathway illuminated a novel signal transduction mechanism in plant cells in response to PFAS. These findings provide comprehensive understandings on the phytotoxicity of PFBA to wheat seedlings and new insights into the impacts of PFAS on plants.

Gecko-Inspired Controllable Adhesive: Structure, Fabrication, and Application.

The gecko can achieve flexible climbing on various vertical walls and even ceilings, which is closely related to its unique foot adhesion system. In the past two decades, the mechanism of the gecko adhesion system has been studied in-depth, and a verity of gecko-inspired adhesives have been proposed. In addition to its strong adhesion, its easy detachment is also the key to achieving efficient climbing locomotion for geckos. A similar controllable adhesion characteristic is also key to the research into artificial gecko-inspired adhesives. In this paper, the structures, fabrication methods, and applications of gecko-inspired controllable adhesives are summarized for future reference in adhesive development. Firstly, the controllable adhesion mechanism of geckos is introduced. Then, the control mechanism, adhesion performance, and preparation methods of gecko-inspired controllable adhesives are described. Subsequently, various successful applications of gecko-inspired controllable adhesives are presented. Finally, future challenges and opportunities to develop gecko-inspired controllable adhesive are presented.

The incidence and impact of atrial fibrillation on hospitalized Coronavirus disease-2019 patients.

BACKGROUND: Since 2019, Coronavirus disease-2019 (COVID-19) has raised unprecedented global health crisis. The incidence and impact of atrial fibrillation (AF) on patients with COVID-19 remain unclearly defined. METHODS: We conducted a retrospective cohort study using ICD-10 codes to identify patients with a primary diagnosis of COVID-19 with or without AF in National Inpatient Sample Database 2020. We compared the outcome of COVID-19 patients with a concurrent diagnosis of AF with those without. HYPOTHESIS: AF will adversely affect the prognosis of hospitalized COVID-19 patients. RESULTS: A total of 211 619 patients with a primary diagnosis of COVID-19 were identified. Among these patients, 31 923 (15.08%) had a secondary diagnosis of AF. Before propensity score matching, COVID-AF cohort was older (75.8 vs. 62.2-year-old, p < .001) and had more men (57.5% vs. 52.0%, p < .001). It is associated with more comorbidities, mainly including diabetes mellitus (43.7% vs. 39.9%, p < .001), hyperlipidemia (54.6% vs. 39.8%, p < .001), chronic kidney disease (34.5% vs. 17.0%, p < .001), coronary artery disease (35.3% vs. 14.4%, p < .001), anemia (27.8% vs. 18.6%, p < .001), and cancer (4.8% vs. 3.4%, p < .001). After performing propensity score match, a total of 31 862 patients were matched within each group. COVID-AF cohort had higher inpatient mortality (22.2% vs. 15.3%, p < .001) and more complications, mainly including cardiac arrest (3.9% vs. 2.3%, p < .001), cardiogenic shock (0.9% vs. 0.3%, p < .001), hemorrhagic stroke (0.4% vs. 0.3%, p = .025), and ischemic stroke (1.3% vs. 0.7%, p < .001). COVID-AF cohort was more costly, with a longer length of stay, and a higher total charge. CONCLUSION: AF is common in patients hospitalized for COVID-19, and is associated with poorer in-hospital mortality, immediate complications and increased healthcare resource utilization.

Takotsubo syndrome and vaccines: a systematic review.

AIMS: Takotsubo syndrome (TTS) is a rare complication of vaccination. In this study, we sought to provide insight into the characteristics of reported TTS induced by vaccination. METHODS AND RESULTS: We did a systematic review, searching PubMed, Embase, Web of Science, Ovid MEDLINE, Journals@Ovid, and Scopus databases up to 26 April 2023 to identify case reports or case series of vaccine-induced TTS. We then extracted and summarized the data from these reports. Eighteen reports were identified, with a total of 19 patients with TTS associated with vaccinations. Of the 19 included patients, the majority were female (n = 13, 68.4%) with a mean age of 56.6 ± 21.9 years. Seventeen patients developed TTS after coronavirus disease 2019 vaccination, 14 of whom received an mRNA vaccination. Two cases of TTS occurred after influenza vaccination. Among the 19 patients, 17 (89.5%) completed transthoracic echocardiography and 16 (84.2%) underwent angiography procedures. Seven patients (36.8%) completed cardiac magnetic resonance imaging. The median time to symptom onset was 2 (inter-quartile range, 1-4) days. The most common symptoms were chest pain (68.4%), dyspnoea (57.9%), and digestive symptoms (31.6%). A total of 57.9% of patients developed nonspecific symptoms such as fatigue, myalgia, diaphoresis, and fever. Among the 16 reported cases of TTS, 15 patients (93.8%) exhibited elevated cardiac troponin levels, while among the nine reported cases, eight patients (88.9%) had elevated natriuretic peptide levels. All patients had electrocardiographic changes: ST-segment change (47.1%), T-wave inversion (58.8%), and prolonged corrected QT interval (35.3%). The most common TTS type was apical ballooning (88.2%). Treatment during hospitalization typically included beta-blockers (44.4%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (33.3%), and diuretics (22.2%). After treatment, 81.3% of patients were discharged with improved symptoms. Among this group, nine patients (56.3%) were reported to have recovered ventricular wall motion during follow-up. Two patients (12.5%) died following vaccination without resuscitation attempts. CONCLUSIONS: TTS is a rare but potentially life-threatening complication of vaccination. Typical TTS symptoms such as chest pain and dyspnoea should be considered alarming symptoms, though nonspecific symptoms are common. The risks of such rare adverse events should be balanced against the risks of infection.

Vole genomics links determinate and indeterminate growth of teeth.

Continuously growing teeth are an important innovation in mammalian evolution, yet genetic regulation of continuous growth by stem cells remains incompletely understood. Dental stem cells responsible for tooth crown growth are lost at the onset of tooth root formation. Genetic signaling that initiates this loss is difficult to study with the ever-growing incisor and rooted molars of mice, the most common mammalian dental model species, because signals for root formation overlap with signals that pattern tooth size and shape (i.e., cusp patterns). Different species of voles (Cricetidae, Rodentia, Glires) have evolved rooted and unrooted molars that have similar size and shape, providing alternative models for studying roots. We assembled a de novo genome of Myodes glareolus, a vole with high-crowned, rooted molars, and performed genomic and transcriptomic analyses in a broad phylogenetic context of Glires (rodents and lagomorphs) to assess differential selection and evolution in tooth forming genes. We identified 15 dental genes with changing synteny relationships and six dental genes undergoing positive selection across Glires, two of which were undergoing positive selection in species with unrooted molars, Dspp and Aqp1. Decreased expression of both genes in prairie voles with unrooted molars compared to bank voles supports the presence of positive selection and may underlie differences in root formation. Bulk transcriptomics analyses of embryonic molar development in bank voles also demonstrated conserved patterns of dental gene expression compared to mice, with species-specific variation likely related to developmental timing and morphological differences between mouse and vole molars. Our results support ongoing evolution of dental genes across Glires, revealing the complex evolutionary background of convergent evolution for ever-growing molars.

Associations of MRI-Derived Glymphatic System Impairment With Global White Matter Damage and Cognitive Impairment in Mild Traumatic Brain Injury: A DTI-ALPS Study.

BACKGROUND: Assessing the glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS) may be helpful for mild traumatic brain injury (mTBI) management. PURPOSE: To assess glymphatic function using DTI-ALPS and its associations with global white matter damage and cognitive impairment in mTBI. STUDY TYPE: Prospective. POPULATION: Thirty-four controls (44.1% female, mean age 49.2 years) and 58 mTBI subjects (43.1% female, mean age 48.7 years), including uncomplicated mTBI (N = 32) and complicated mTBI (N = 26). FIELD STRENGTH/SEQUENCE: 3-T, single-shot echo-planar imaging sequence. ASSESSMENT: Magnetic resonance imaging (MRI) was done within 1 month since injury. DTI-ALPS was performed to assess glymphatic function, and peak width of skeletonized mean diffusivity (PSMD) was used to assess global white matter damage. Cognitive tests included Auditory Verbal Learning Test and Digit Span Test (forward and backward). STATISTICAL TESTS: Neuroimaging findings comparisons were done between mTBI and control groups. Partial correlation and multivariable linear regression assessed the associations between DTI-ALPS, PSMD, and cognitive impairment. Mediation effects of PSMD on the relationship between DTI-ALPS and cognitive impairment were explored. P-value <0.05 was considered statistically significant, except for cognitive correlational analyses with a Bonferroni-corrected P-value set at 0.05/3 ≈ 0.017. RESULTS: mTBI showed lower DTI-ALPS and higher PSMD, especially in complicated mTBI. DTI-ALPS was significantly correlated with verbal memory (r = 0.566), attention abilities (r = 0.792), executive function (r = 0.618), and PSMD (r = -0.533). DTI-ALPS was associated with verbal memory (ß = 8.77, 95% confidence interval [CI] 5.00, 12.54), attention abilities (ß = 5.67, 95% CI 4.56, 6.97), executive function (ß = 2.34, 95% CI 1.49, 3.20), and PSMD (ß = -0.79, 95% CI -1.15, -0.43). PSMD mediated 46.29%, 20.46%, and 24.36% of the effects for the relationship between DTI-ALPS and verbal memory, attention abilities, and executive function. DATA CONCLUSION: Glymphatic function may be impaired in mTBI reflected by DTI-ALPS. Glymphatic dysfunction may cause cognitive impairment related to global white matter damage after mTBI. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.

Multistimuli-Responsive Actuators Derived from Natural Materials for Entirely Biodegradable and Programmable Untethered Soft Robots.

Untethered soft robots have attracted growing attention due to their safe interaction with living organisms, good flexibility, and accurate remote control. However, the materials involved are often nonbiodegradable or are derived from nonrenewable resources, leading to serious environmental problems. Here, we report a biomass-based multistimuli-responsive actuator based on cuttlefish ink nanoparticles (CINPs), wood-derived cellulose nanofiber (CNF), and bioderived polylactic acid (PLA). Taking advantage of the good photothermal conversion performance and exceptionally hygroscopic sensitivity of the CINPs/CNF composite (CICC) layer and the opposite thermally induced deformation behavior between the CICC layer and PLA layer, the soft actuator exhibits reversible deformation behaviors under near-infrared (NIR) light, humidity, and temperature stimuli, respectively. By introducing patterned or alignment structures and combining them with a macroscopic reassembly strategy, diverse programmable shape-morphing from 2D to 3D such as letter-shape, coiling, self-folding, and more sophisticated 3D deformations have been demonstrated. All of these deformations can be successfully predicted by finite element analysis (FEA) . Furthermore, this actuator has been further applied as an untethered grasping robot, weightlifting robot, and climbing robot capable of climbing a vertical pole. Such actuators consisting entirely of biodegradable materials will offer a sustainable future for untethered soft robots.

AaABI5 transcription factor mediates light and abscisic acid signaling to promote anti-malarial drug artemisinin biosynthesis in Artemisia annua.

Artemisia annua, a member of the Asteraceae family, remains the primary source of artemisinin. However, the artemisinin content in the existing varieties of this plant is very low. In this study, we found that the environmental factors light and phytohormone abscisic acid (ABA) could synergistically promote the expression of artemisinin biosynthetic genes. Notably, the increased expression levels of those genes regulated by ABA depended on light. Gene expression analysis found that AaABI5, a transcription factor belonging to the basic leucine zipper (bZIP) family, was inducible by the light and ABA treatment. Analysis of AaABI5-overexpressing and -suppressing lines suggested that AaABI5 could enhance artemisinin biosynthesis and activate the expression of four core biosynthetic genes. In addition, the key regulator of light-induced artemisinin biosynthesis, AaHY5, could bind to the promoter of AaABI5 and activate its expression. In conclusion, our results demonstrated that AaABI5 acts as an important molecular junction for the synergistic promotion of artemisinin biosynthesis by light and ABA signals, which provides a candidate gene for developing new germplasms of high-quality A. annua.

Incidence and Impact of Acute Pericarditis in Hospitalized Patients With COVID-19.

Background Acute pericarditis (AP) is considered a cardiovascular complication in patients with COVID-19. We aimed to ass-ess the incidence, associated complications, and clinical impact of AP on hospitalized patients with COVID-19. Methods and Results In this retrospective cohort study, International Classification of Diseases, Tenthth Revision, Clinical Modification (ICD-10) codes were used to identify patients with COVID-19 with or without AP in the National Inpatient Sample 2020 database. We compared outcomes between AP and non-AP groups before and after propensity-score matching for patient and hospital demographics and relevant comorbidities. A total of 211 619 patients with a primary diagnosis of COVID-19 were identified, including 983 (0.46%) patients who had a secondary diagnosis of AP. Before matching, patients with COVID-19 with AP were younger (59.93±19.24 years old versus 64.29±16.82 years old) and more likely to have anemia (40.5% versus 19.9%), cancer (6.7% versus 3.6%), and chronic kidney disease (29.3% versus 19.6%) (all P<0.05). After matching, patients with COVID-19 with AP (n=980), when compared with the matched non-AP group (n=2936), had higher rates of mortality (21.3% versus 11.1%, P<0.001), cardiac arrest (5.0% versus 2.6%, P<0.001), cardiogenic shock (4.2% versus 0.5%, P<0.001), ventricular arrhythmia (4.7% versus 1.9%, P<0.001), acute kidney injury (38.3% versus 28.9%, P<0.001), acute congestive heart failure (14.3% versus 4.8%, P<0.001), and longer length of stay (7.00±10.00 days versus 5.00±7.00 days, P<0.001) and higher total charges ($75066.5±$130831.3 versus $44824.0±$63660.5, P<0.001). Conclusions In hospitalized patients with COVID-19, AP is a rare but severe in-hospital complication and is associated with worse in-hospital outcomes.

Left bundle branch area pacing for heart failure patients requiring cardiac resynchronization therapy: A meta-analysis.

INTRODUCTION: Left bundle branch area pacing (LBBP) is a novel conduction system pacing method to achieve effective physiological pacing and an alternative to cardiac resynchronization therapy (CRT) with biventricular pacing (BVP) for patients with heart failure with reduced ejection fraction (HFrEF). We conduted this meta-analysis and systemic review to review current data comparing BVP and LBBP in patients with HFrEF and indications for CRT. METHODS: We searched PubMed/Medline, Web of Science, and Cochrane Library from the inception of the database to November 2022. All studies that compared LBBP with BVP in patients with HFrEF and indications for CRT were included. Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated risk ratios (RRs) with the Mantel-Haenszel method and mean difference (MD) with inverse variance using random effect models. We assessed heterogeneity using the I2 index, with I2 > 50% indicating significant heterogeneity. RESULTS: Ten studies (9 observational studies and 1 randomized controlled trial; 616 patients; 15 centers) published between 2020 and 2022 were included. We observed a shorter fluoroscopy time (MD: 9.68, 95% confidence interval [CI]: 4.49-14.87, I2 = 95%, p < .01, minutes) as well as a shorter procedural time (MD 33.68, 95% CI: 17.80-49.55, I2 = 73%, p < .01, minutes) during the implantation of LBBP CRT compared to conventional BVP CRT. LBBP was shown to have a greater reduction in QRS duration (MD 25.13, 95% CI: 20.06-30.20, I2 = 51%, p < .01, milliseconds), a greater left ventricular ejection fraction improvement (MD: 5.80, 95% CI: 4.81-6.78, I2 = 0%, p < .01, percentage), and a greater left ventricular end-diastolic diameter reduction (MD: 2.11, 95% CI: 0.12-4.10, I2 = 18%, p = .04, millimeter). There was a greater improvement in New York Heart Association function class with LBBP (MD: 0.37, 95% CI: 0.05-0.68, I2 = 61%, p = .02). LBBP was also associated with a lower risk of a composite of heart failure hospitalizations (HFH) and all-cause mortality (RR: 0.48, 95% CI: 0.25-0.90, I2 = 0%, p = .02) driven by reduced HFH (RR: 0.39, 95% CI: 0.19-0.82, I2 = 0%, p = .01). However, all-cause mortality rates were low in both groups (1.52% vs. 1.13%) and similar (RR: 0.98, 95% CI: 0.21-4.68, I2 = 0%, p = .87). CONCLUSION: This meta-analysis of primarily nonrandomized studies suggests that LBBP is associated with a greater improvement in left ventricular systolic function and a lower rate of HFH compared to BVP. There was uniformity of these findings in all of the included studies. However, it would be premature to conclude based solely on the current meta-analysis alone, given the limitations stated. Dedicated, well-designed, randomized controlled trials and observational studies are needed to elucidate better the comparative long-term efficacy and safety of LBBP CRT versus BIV CRT.

Identification and Prioritization of Environmental Organic Pollutants: From an Analytical and Toxicological Perspective.

Exposure to environmental organic pollutants has triggered significant ecological impacts and adverse health outcomes, which have been received substantial and increasing attention. The contribution of unidentified chemical components is considered as the most significant knowledge gap in understanding the combined effects of pollutant mixtures. To address this issue, remarkable analytical breakthroughs have recently been made. In this review, the basic principles on recognition of environmental organic pollutants are overviewed. Complementary analytical methodologies (i.e., quantitative structure-activity relationship prediction, mass spectrometric nontarget screening, and effect-directed analysis) and experimental platforms are briefly described. The stages of technique development and/or essential parts of the analytical workflow for each of the methodologies are then reviewed. Finally, plausible technique paths and applications of the future nontarget screening methods, interdisciplinary techniques for achieving toxicant identification, and burgeoning strategies on risk assessment of chemical cocktails are discussed.