AF Group Research Articles

Abstract 4129223: Large Language Modeling-Enabled Analysis of Atrial Fibrillation Topics and Sentiments on Social Media

Purpose: We utilized large language modeling (LLM) and automated topic modeling techniques to describe public perceptions regarding AF on Reddit, a social media platform. Methods: In this qualitative study, we curated all AF-related discussions on Reddit from 2006 to 2023 by searching for all posts and comments containing AF-related terms (“atrial fibrillation”, “afib”, and “atrial flutter”). Discussions were embedded using a state-of-the-art embedding model (BAAI/bge-base-en-v1.5). Embeddings are reduced in dimensionality using Uniform Manifold Approximation and Project and clustered using K-Means Clustering to find topics and groups. Topic and group labels are enhanced using large language models (Llama2 and GPT4, respectively). Results: We identified a total of 86,323 discussions related to AF from 38,183 unique users between April 14, 2006 and November 20, 2023. Discussions around wearables and ablations increased over time, while discussions around anticoagulation had periodic spikes. The topic modeling pipeline automatically identified 64 topics and 9 groups (Figure 1). Groups emphasized the following themes: lifestyle factors and triggers associated with AF (groups 1, 5, 7); patient experiences with management strategies including anticoagulation, rate control, pharmacological rhythm control, and ablation (groups 2, 4, 5); experiences with wearable devices (group 8); psychological burden of living with AF (group 6); and online advertisements for AF-related medications (groups 3, 9). Conclusions: Our AI-enabled topic modeling analysis revealed public perceptions about AF including triggers, experiences with different management strategies, impact of wearables, and psychological burden of the diagnosis, which may help guide potential strategies for improving shared decision making around the AF patient journey.

Pulsed Field Ablation in Atrial Fibrillation: Initial Experience of the Efficacy and Safety in Pulmonary Vein Isolation and Beyond

Regional differences in pulsed field ablation (PFA) adoption for pulmonary vein isolation (PVI) with additional posterior wall ablation (PWA) in Asia remains unknown. We hereby report our experience on the safety and efficacy of PFA in AF ablation. Consecutive AF patients who underwent PFA from September 2022 to January 2024 were included. The primary efficacy endpoint was freedom from atrial arrhythmia recurrence after a 90-day blanking period at 12 months. Safety endpoints included 30 days of all-cause death, cardiac tamponade, stroke, myocardial infarction, and heart failure hospitalization. One hundred and one (72.3% males, 79.2% pAF) patients underwent PFA for AF. Thirty-one (30.7%) had structural heart disease with mean LVEF of 57.4 ± 8.1% and CHA2DS2-VASc score of 1.4 ± 1.3. Twenty-nine (28.7%) underwent additional PWA (PVI + PWA) using PFA. PWA was acutely successful in all patients. Patients who underwent PWA were more likely to have persistent AF and require general anesthesia and electroanatomic mapping (all p < 0.05). Total PFA applications for PVI, LA dwell time, procedural time, and fluoroscopy time were similar between the PVI-only and PVI + PWA groups (all p > 0.05). The 1-year atrial arrhythmia recurrence rates were 10% for pAF and 21% for the persistent AF group. The primary efficacy endpoint was not significantly different between the PVI-only and PVI+PWA groups (12-month KM estimates 90.3% [95% CI, 83.3–97.3] and 82.8% [95% CI, 68.1–97.4], respectively). There were no complications related to PFA use. PFA can be safely, effectively, and efficiently adopted for AF ablation. Additional PWA, if pursued, had similar procedural metrics to the PVI-only strategy without increased complications.

Association Between Atrial Fibrillation and Long-term Mortality in Acute MI Patients

Background: AF is a common complication of an acute MI (AMI) and goes along with adverse events. Nevertheless, the therapeutical guidelines and pharmacological possibilities have improved over the past years. Therefore, this contemporary study aimed to clarify the effect of AF on long-term mortality in patients with incident AMI. Methods: This study included 2,313 patients aged 25–84 years with initial AMI that occurred from 2009 until 2017, documented within the population-based Augsburg Myocardial Infarction Registry. Patients were monitored from hospital admission, with a median follow-up duration of 4.5 years (interquartile range 4.4 years). Survival analysis and multivariable Cox regression analysis were conducted to explore the relationship between AF and long-term all-cause and cardiovascular disease mortality. Results: Altogether, 156 individuals had AF on their admission ECG, while the remaining 2,157 presented with sinus rhythm (SR). Patients with AF were significantly older, more frequently had arterial hypertension, non-ST-segment elevation MI, worse kidney function, smaller AMIs, and were more often former and non-smokers. An increased long-term all-cause mortality was observed among the AF group. (AF patients 39.1%, SR group 16.7%), Upon multivariable adjustment, a HR of 1.40 (95% CI [1.05–1.87]; p=0.023) was calculated when comparing the AF with SR patients. Conclusion: An independently increased risk of long-term mortality for patients with AF compared with patients with SR in case of incident AMI was identified. Therefore, AF should be considered as a serious risk factor in AMI patients, and must be treated aggressively to reduce mortality risk.

Secretomes from human epicardial adipocytes modulate atrial lymphatics and atrial fibrosis

Abstract Background Cardiac lymphatics maintains myocardial fluid and immune cell homeostasis. Downregulation of cardiac lymphatics leads to cardiac dysfunction through impairment of inflammation and edema. On the other hand, it is well known that adipose tissue accumulation causes lymphatic dysfunction and impairs lymphedema. Purpose We evaluated the expression of atrial lymphatics in human left atrial appendage (LAA) histologically and biologically. Subsequently, we examined secretomes from epicardial adipose tissue (EAT)-derived adipocytes and validated if they change atrial lymphatics expression using ex vivo Organo-culture system. Methods Human LAA samples were collected from forty-two patients during cardiovascular surgery. They were categorized into the sinus rhythm (SR) group (n=16, 73.1±10.4 years), the paroxysmal AF (PAF) group (n=13, 69.8±12.6 years) and the persistent AF (PeAF) group (n=13, 71.2±6.5 years). Human EAT were also excised from patients with and without AF (SR; n=5, AF; n=11) during cardiovascular surgery. Preadipocytes were extracted from EAT by homogenization and collagenase treatment, and cultured to confluence. After differentiation and maturation to adipocytes, cell culture supernatant (CCS) was collected, and was dropped onto the epicardial side of left atrial tissues excised from 8 weeks old male rats for 7 days using an ex vivo organo-culture system. Results In human LAA samples, mRNA expression of lymphangiogenesis-related genes (LYVE1, PROX1, VEGFC, and VEGFR3) was significantly lower in the PeAF group compared to the SR group (p=0.0370, <0.0001, 0.0157, and 0.0009). The number of LYVE1-positive atrial lymphatic endothelial cells (LECs) was also significantly lower in the PeAF group compared to the SR group and the PAF group (p=0.0186 and 0.038). There was a negative correlation between the number of LYVE1-positive atrial LECs and the area percentage of atrial myocardial fibrosis (r=-0.5350, p<0.001). In the experiment using organo-culture system, lymphangiogenesis-related genes expression (Lyve1, Prox1, Vegfc, and Vegfr3) of rat atria treated with CCS of adipocytes from AF patients was significantly lower than those from SR patients (p=0.0391, 0.0100, 0.0034, and 0.0338). Furthermore, the CCS of adipocytes from AF patients contained higher protein levels of leptin, which is known to suppress lymphangiogenesis (p=0.0357). Leptin treatment (100ng/ml) on rat atria also decreased lymphangiogenesis-related genes expression such as Lyve1, Prox1, Vegfc, and Vegfr3 (p=0.0413, < 0.0001, <0.0001, and 0.0190). Conclusions Our study with human LAA demonstrated that atrial lymphatics interact with atrial myocardial fibrosis/progression of AF. Furthermore, our findings indicate that secretomes from EAT-derived adipocytes regulate atrial lymphatics expression, and leptin plays an important role in modulating atrial lymphangiogenesis.

Effects of artificial diets on lipid and glucose metabolism, antioxidative capacity, and inflammation in the liver of mandarin fish (Siniperca chuatsi)

The mandarin fish (Siniperca chuatsi) is a typical carnivorous fish, which has been able to consume artificial diets after domestication in recent years. However, the potential health consequences of artificial diets in mandarin fish remain unclear. This study aimed to elucidate the molecular mechanisms underlying these concerns. Fish (initial weight: 25.1 ± 0.1 g) were fed with natural (CON group) or artificial diets (AF group) for 8 weeks. Each diet was randomly distributed to sextuplicate circular tanks (300 L) with 40 fish in each tank. The transcriptome analysis revealed significant changes in metabolism-related pathways, particularly those involved in lipid and carbohydrate metabolism. Further investigation confirmed that the artificial diets significantly increased hepatic triglyceride content and fatty acid synthase activity. The artificial diets also significantly increased hepatic glycogen and glucose-6-phosphatase activity. Furthermore, the artificial diets significantly increased hepatic malondialdehyde levels, indicating increased oxidative stress. Antioxidant defense enzyme activities and the expression of antioxidant stress-related genes were significantly decreased. Additionally, the artificial diets significantly increased the expression of proinflammatory genes, including interleukin 1 beta and interferon-gamma. These findings collectively demonstrated that the artificial diets disrupted hepatic lipid and glucose metabolism, leading to oxidative stress and inflammation, thus affecting the health status of mandarin fish.

Oral Diltiazem Prophylaxis for Atrial Fibrillation in Patients Undergoing Robotic Lobectomy

BackgroundAtrial fibrillation (AF) prophylaxis with diltiazem has not been studied after robotic lobectomies. We aimed to determine whether prophylaxis with oral diltiazem is associated with a lower rate of AF after robotic lobectomy. MethodsA retrospective review of all robotic lobectomies during an 8-year period was conducted. After our practice protocol change (September 2014), patients undergoing lobectomy were prescribed prophylactic oral diltiazem postoperatively to reduce the incidence of AF. Demographics, operative variables, smoking history, diagnosis, and rate of postoperative AF were collected. Study groups were defined as group 1 (operated before protocol change without postoperative oral diltiazem prophylaxis administered) and group 2 (operated after protocol change and postoperative oral diltiazem prophylaxis administered). Statistical analysis included Student t test, χ2 test, and univariate/multivariable and propensity score matching analysis. ResultsAfter excluding patients with history of AF (n = 48), beta-blocker/calcium-channel blocker use (n = 177), and patients who did not receive diltiazem prophylaxis after protocol change (n = 60), 333 remained for analysis (group 1 [n = 133], group 2 [n =200]). There were no significant differences regarding demographics, smoking status, or operative characteristics. Overall length of stay was similar between groups (P = .2). There was no difference in the rate of postoperative AF (group 1, 7% [9 of 133] vs group 2, 8% [16 of 200]; P = .6). After multivariable analysis, only male sex showed significantly higher odds of postoperative AF (odds ratio, 3.24, 95% CI, 1.18-8.86, P = .02). ConclusionsOral diltiazem prophylaxis after robotic lobectomy was not associated with a lower rate of postoperative AF. Its use could be tailored to those at higher risk of postoperative AF to achieve its therapeutic benefit.

Adjusted versus Targeted Fortification in Extremely Low Birth Weight Preterm Infants: Fortin Study-A Randomized Clinical Trial.

Fortified human milk is the first choice for preterm infants. Although individualized fortification is recommended, the optimal method for this population remains uncertain. We conducted a comparative study assessing the growth effects of adjusted (AF) and targeted fortification (TF) in extremely low birth weight (ELBW) infants. This single-center, randomized, controlled clinical trial was conducted at a tertiary neonatal unit in Spain. Eligible participants were premature infants with a birthweight of <1000 g exclusively fed with human milk. A total of 38 patients were enrolled, 15 of them randomized to AF group and 23 to TF group. AF was based on blood urea nitrogen (BUN) concentration and TF on human milk analysis. The primary outcome was weight gain velocity (g/kg/day). No significant differences were found in weight gain velocity at 28 days, at 36 weeks of postmenstrual age, at discharge, nor during the intervention. Protein intake was significantly higher in the AF group (5.02 g/kg/day vs. 4.48 g/kg/day, p = 0.001). No differences were found in the lipid, carbohydrate, and energy intake; in the weight z score change between the different time points; nor in the length and head circumference growth. Both AF and TF are comparable methods of fortification and provide the appropriate growth rate in ELBW infants.

Accumulated β-catenin is associated with human atrial fibrosis and atrial fibrillation

BackgroundAtrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by β-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of β-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues .MethodsWe compared the difference of β-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of β-catenin in the development of AF was also explored in mice and primary cells.ResultsFirstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of β-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, β-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3β (GSK-3β) and Adenomatous Polyposis Coli (APC), which participated in the degradation of β-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting β-catenin expression in the AF model mice.ConclusionsBased on human atrial pathological and molecular analyses, our findings provided evidence that β-catenin was associated with atrial fibrosis and AF progression.

Exploring the Effects of an Alfalfa Leaf-Derived Adsorbent on Microbial Community, Ileal Morphology, Barrier Function, and Immunity in Turkey Poults during Chronic Aflatoxin B1 Exposure.

This article follows-up on our recently published work, which evaluated the impact of the addition of an alfalfa leaf-derived adsorbent in the aflatoxin B1 (AFB1)-contaminated diet in regard to the production parameters, blood cell count, serum biochemistry, liver enzymes, and liver histology of turkey poults. This paper presents complementary results on microbial community, ileal morphology, barrier function, and immunity. For this purpose, 350 1-day-old female turkey poults were randomly distributed into five groups: (1) Control, AFB1-free diet; (2) AF, AFB1-contaminated diet at 250 ng/g; (3) alfalfa, AFB1-free diet + 0.5% (w/w) adsorbent; (4) alfalfa + AF, AFB1-contaminated diet at 250 ng/g + 0.5% (w/w) adsorbent; and (5) YCW + AF, AFB1-contaminated diet at 250 ng/g + 0.5% (w/w) commercial yeast cell wall-based adsorbent (reference group). In general, in the AF group, the growth of opportunistic pathogens was promoted, which lead to gut dysbacteriosis, mainly influenced by Streptococcus lutetiensis. Conversely, a significant increase in beneficial bacteria (Faecalibacterium and Coprococcus catus) was promoted by the addition of the plant-based adsorbent. Moreover, the AF group had the lowest villus height and a compromised barrier function, as evidenced by a significant (p < 0.05) increase in fluorescein isothiocyanate dextran (FITC-d), but these negative effects were almost reversed by the addition of the alfalfa adsorbent. Furthermore, the AF + YCW and alfalfa + AF groups exhibited a significant increase in the cutaneous basophil hypersensitivity response compared to the rest of the experimental groups. Taken together, these results pointed out that the alfalfa counteracts the adverse effects of AFB1 in poults, facilitating the colonization of beneficial bacteria and improving the barrier function of the turkey poults.

Left atrial reservoir strain is a marker of atrial fibrotic remodeling in patients undergoing cardiovascular surgery: Analysis of gene expression.

Left atrial strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DSTE) is considered to be a marker of LA structural remodeling, but it remains unsettled. We investigated the potential usefulness and clinical relevance of LAS to detect atrial remodeling including fibrosis by analyzing gene expression in cardiovascular surgery patients. Preoperative 2DSTE was performed in 131 patients (92 patients with sinus rhythm [SR] patients including paroxysmal AF [PAF], 39 atrial fibrillation [AF]) undergoing cardiovascular surgery. Atrial samples were obtained from the left atrial appendages, and mRNA expression level was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases (24 PAF, 35 AF). Mean value of left atrial reservoir strain (mLASr) correlated with left atrial volume index (LAVI), and left atrial conduit strain (mLAScd). mLASr also correlated with left atrial contractile strain (mLASct) in SR patients including PAF. mLASr was significantly lower, and LAVI was higher, in the AF group, compared with SR patients including PAF. The expression of COL1A1 mRNA encoding collagen type I α1 significantly increased in AF patients (p = 0.031). mLASr negatively correlated with COL1A1 expression level, and multivariate regression analysis showed that mLASr was an independent predictor of atrial COL1A1 expression level, even after adjusting for age, sex, and BMI. But, neither mLAScd / mLASct nor LAVI (bp) correlated with COL1A1 gene expression. The expression level of COL1A1 mRNA strongly correlated with ECM-related genes (COL3A1, FN1). It also correlated ECM degradation-related genes (MMP2, TIMP1, and TIMP2), pro-fibrogenic cytokines (TGFB1 encoding TGFβ1, END1, PDGFD, CTGF), oxidant stress-related genes (NOX2, NOX4), ACE, inflammation-related genes (NLRP, IL1B, MCP-1), and apoptosis (BAX). Among the fibrosis-related genes examined, univariable regression analysis showed that log (COL1A1) was associated with log (TGFB1) (adjusted R2 = 0.685, p<0.001), log (NOX4) (adjusted R2 = 0.622, p<0.001), log (NOX2) (adjusted R2 = 0.611, p<0.001), suggesting that TGFB1 and NOX4 was the potent independent determinants of COL1A1 expression level. mLASr negatively correlated with the ECM-related genes, and fibrosis-related gene expression level including TGFB1, NOX2, and NLRP3 in PAF patients. PAF patients with low mLASr had higher expression of the fibrosis-related gene expression, compared with those with high mLASr. These results suggest that LASr correlates with atrial COL1A1 gene expression associated with fibrosis-related gene expression. Patients with low LASr exhibit increased atrial fibrosis-related gene expression, even those with PAF, highlighting the utility of LAS as a marker for LA fibrosis in cardiovascular surgery patients.

Comprehensive Analysis of Immune Cell Infiltration and M2-Like Macrophage Biomarker Expression Patterns in Atrial Fibrillation.

Macrophages play a crucial role in the progression of AF, closely linked to atrial inflammation and myocardial fibrosis. However, the functions and molecular mechanisms of different phenotypic macrophages in AF are not well understood. This study aims to analyze the infiltration characteristics of atrial immune cells in AF patients and further explore the role and molecular expression patterns of M2 macrophage-related genes in AF. This study integrates single-cell and large-scale sequencing data to analyze immune cell infiltration and molecular characterization of the LAA in patients with AF, using SR as a control group. CIBERSORT assesses immune cell types in LAA tissues; WGCNA identifies signature genes; cell clustering analyzes cell types and subpopulations; cell communication explores macrophage interactions; hdWGCNA identifies M2 macrophage gene modules in AF. AF biomarkers are identified using LASSO and Random Forest, validated with ROC curves and RT-qPCR. Potential molecular mechanisms are inferred through TF-miRNA-mRNA networks and single-gene enrichment analyses. Myeloid cell subsets varied considerably between the AF and SR groups, with a significant increase in M2 macrophages in the AF group. Signals of inflammation and matrix remodeling were observed in AF. M2 macrophage-related genes IGF1, PDK4, RAB13, and TMEM176B were identified as AF biomarkers, with RAB13 and TMEM176B being novel markers. A TF-miRNA-mRNA network was constructed using target genes, which are enriched in the PPAR signaling pathway and fatty acid metabolism. Over infiltration of M2 macrophages may be an important factor in the progression of AF. The M2 macrophage-related genes IGF1, RAB13, TMEM176B and PDK4 may regulate the progression of AF through the PPAR signaling pathway and fatty acid metabolism.

Comparison of alfentanil and fentanyl in painless colonoscopy in children

[Objective] To explore the safety and efficacy of alfentanil and fentanyl combined with propofol in painless colonoscopy in children. [Methods] 60 children aged 3-7 years old who were going to do colonoscopy in our hospital were randomly divided into alfentanil group (AF group) and fentanyl group (F group), with 30 cases in each group. The dosage of alfentanil 10ug/kg and fentanyl 2ug/kg respectively were used in both groups. The recovery time, induced cough, vital signs, physical activity, drug supplementation, postoperative adverse reactions and doctor satisfaction of the two groups of children were observed and recorded. [Results] The recovery time of AF group was shorter than that of F group, which was (11.40±4.33) minutes and (9.37±2.81) minutes respectively (P&lt; 0.05). The induced cough in AF group was less than that in F group (P&lt; 0.05). AF group had more body motion than F group (P&lt; 0.05). There were no significant differences in blood pressure, heart rate, oxygen saturation, respiratory rate and other vital signs between the two groups (P&gt; 0.05), but the values of vital signs at all observation points in the two groups were lower than those before anesthesia. No adverse reactions occurred in the two groups, and there was no significant difference in the satisfaction of doctors between the two groups. [Conclusion] Both alfentanil and fentanyl can be effectively used in painless colonoscopy in children. However, alfentanil is more suitable for painless colonoscopy than fentanyl due to its shorter resuscitation time, lower incidence of induced cough and no increased risk of adverse reactions.

Exploring the influence and mechanism of different frying methods on the flavor quality of low-salt sour meat

To obtain nutritious, healthy, and flavor-enriched sour meat products, the effects of different frying methods (microwave, air-frying, and traditional frying) on the flavor quality of low-salt sour meat were evaluated using metabolomics and other flavor analysis techniques. The pH value of the sour meat rose dramatically, while the TBARS value dropped significantly after frying. E-nose and E-tongue results showed that air-frying could reduce acidity and improve umami. The comprehensive analysis of all samples revealed the identification of 107 volatile flavor compounds, including 10 unique aroma compounds that were specifically detected in the AF group. Additionally, the air frying process notably increased the free amino acid and nucleotide concentrations in sour meat by 53.58% and 159.29%, respectively, while causing a significant reduction in both fatty acid and lactic acid content by 22.84% and 49.29%, respectively. All three frying methods altered the flavor of the samples, but air frying performed better in terms of flavor and texture.

Pharmacokinetics and safety of asciminib (ASC) in pediatric patients (pts) with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia in chronic phase (CML-CP): Interim results from the ASC4KIDS study.

6562 Background: For pediatric pts with Ph+ CML-CP, treatment options with improved efficacy and long-term safety are needed. ASC is a first-in-class tyrosine kinase inhibitor (TKI) Specifically Targeting the ABL Myristoyl Pocket (STAMP), approved for adults with Ph+ CML-CP treated with ≥2 prior TKIs. The phase Ib/II ASC4KIDS study (NCT04925479) aims to characterize the pharmacokinetics (PK) and long-term safety profile of ASC in pediatric pts. Methods: This multi-center, open-label study included pts aged 1–&lt;18 years (yrs) with Ph+ CML-CP, without T315I mutation, treated with ≥1 prior TKIs. The primary endpoint is to characterize the PK of ASC in pediatric pts and identify a dose using the pediatric formulation (PF, taken with food) leading to an ASC exposure comparable to the adult dose and formulation (AF, 40 mg tablet twice daily [BID] fasted). Secondary endpoints include safety, molecular responses and acceptability/palatability of the pediatric formulation. In an exploratory group, pts 14‒&lt;18 yrs old were treated with the AF (fasted). In study Part 1 (dose-determining cohort), pts received PF at an initial dose of 1.3 mg/kg BID (with food) to assess ASC exposure (measured by area under the curve from dosing to the time of the last measured concentration [AUClast] and maximum plasma concentration [Cmax]) and safety. In Part 2 (dose expansion cohort), additional pts will be treated with the dose confirmed in Part 1 (across Part 1 + Part 2; 10 pts per age group: 1‒&lt;12 yrs and 12‒&lt;18 yrs, for a total of 20 pts). In Part 3, another 10 pts will be enrolled (5 pts per age group), who will receive the same total ASC dose as a once daily regimen. Results: 4 and 9 pts were enrolled in the Part 1 AF and PF groups, respectively. At interim data cutoff (03-Aug-2023), all pts were receiving ongoing treatment. Age ranges were 15‒16 yrs (AF group) and 2‒16 yrs (PF group). Averaged ASC exposure in the AF group was comparable to that observed in adults. 3/4 (75.0%) pts on ASC AF experienced adverse events (AEs); none were Grade ≥3. There were no new safety signals as compared to the known safety profile of ASC in adults. Averaged ASC exposure in the PF group was comparable to that observed in adults (median AUClast: 5051 vs 5130 hr*ng/mL; median Cmax: 711 vs 939 ng/mL, respectively). Based on these data, the PF dose of 1.3 mg/kg BID (with food) was confirmed as the pediatric dose. All pts on ASC PF experienced AEs; Grade ≥3 AEs were reported for 2/9 pts (22.2%). No predefined dose-limiting toxicities, serious AEs, or AEs leading to discontinuation were reported in either group. Conclusions: ASC exposure with the PF (with food) in pediatric pts was comparable to that of adult pts treated with ASC 40 mg BID (fasted); the confirmed PF dose of 1.3 mg/kg BID will continue to be tested in Part 2 of the study. ASC was safe and well tolerated in pediatric pts. Clinical trial information: NCT04925479 .

Ultraviolet-induced red fluorescence in androgenetic alopecia-indicating alterations in microbial composition.

Ultraviolet (UV)-induced fluorescence technology is widely used in dermatology to identify microbial infections. Our clinical observations under an ultraviolet-induced fluorescent dermatoscope (UVFD) showed red fluorescence on the scalps of androgenetic alopecia (AGA) patients. In this study, based on the hypothesis that microbes are induced to emit red fluorescence under UV light, we aimed to explore the microbial disparities between the AGA fluorescent area (AF group) and AGA non-fluorescent area (ANF group). Scalp swab samples were collected from 36 AGA patients, including both fluorescent and non-fluorescent areas. The bacterial communities on the scalp were analyzed by 16S rRNA gene sequencing and bioinformatics analysis, as well as through microbial culture methods. Significant variations were observed in microbial evenness, abundance composition, and functional predictions between fluorescent and non-fluorescent areas. Sequencing results highlighted significant differences in Cutibacterium abundance between these areas (34.06% and 21.36%, respectively; p<0.05). Furthermore, cultured red fluorescent colonies primarily consisted of Cutibacterium spp., Cutibacterium acnes, Staphylococcus epidermidis, and Micrococcus spp. This is the first study to investigate scalp red fluorescence, highlighting microbial composition variability across different scalp regions. These findings may provide novel insights into the microbiological mechanisms of AGA.

Type III Endoleak Incidence and Outcomes in Endovascular Aortic Repair: Comparison of Anatomical and Proximal Fixation Devices.

To evaluate the influence of endograft fixation type on the incidence, treatment, and outcomes of type III endoleaks (TIIIELs). Abdominal aortic aneurysms (AAAs) treated with bifurcated endografts between 1994 and 2020 were prospectively collected and reviewed. The endograft included were classified as "Anatomical Fixation" (AF) (Powerlink [Endologix] and AFX [Endologix]) or "Proximal Fixation" (PF). The primary outcome was the incidence of TIIIEL over time, stratified by fixation type. Secondary outcomes included between-group comparisons of baseline characteristics, intraoperative details during TIIIEL correction, and survival analysis after TIIIEL diagnosis. A total of 2065 endovascular aneurysm repairs were performed: 872 (42.2%) with AF and 1193 (57.8%) with PF devices. The estimated incidence of TIIIEL at 1, 5, and 10 years was 0.4%, 4.2%, and 7.3%, and 0.5%, 3.2%, and 4.6% for AF and PF, respectively (p=0.157), and fixation type was not associated with TIIIEL development in the competing risk regression model (p=0.101). The cumulative overall survival rate in patients diagnosed with TIIIEL did not differ significantly between the groups (p=0.077). The rate of recurrent TIIIELs was significantly lower in the AF group (7.1% vs 22.7%; p=0.044); however, no significant difference was found in secondary reintervention between the two groups (11.9% vs 27.3%, p=0.074). Patients with angulated and calcified aortic neck (SHR 3.4, 95% CI 1.2-9.6, p=0.022) and larger aneurysms (SHR 1.2; 95% CI 1.1-1.3; p<0.001) had a higher risk of TIIIEL. Likewise, the use of three or more endograft components increased the risk of TIIIEL by 3.1 times (SHR 3.1; 95% CI 1.7-5.4; p<0.001). The occurrence of TIIIELs was not affected by the type of endograft fixation. For larger abdominal aortic aneurysms (AAAs) and aneurysms with angulated and calcified aortic necks, there is a higher likelihood of developing TIIIELs during follow-up, regardless of the endograft type used. The type of fixation does not influence the incidence of TIII ELs. EVAR in larger AAAs and aneurysms with angulated and calcified aortic necks have a higher risk of developing TIII EL. Moreover, the risk of TIII EL is considerably increased by the use of three or more modular components.

Association between atrial fibrillation and heart failure patient reported outcomes across the ejection fraction spectrum

BackgroundAtrial fibrillation (AF) is common in patients with heart failure (HF) and is associated with worse clinical outcomes. We evaluated the relationship between AF and longitudinal changes in health-related quality of life (HRQoL) measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) in both HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). MethodsThis is a post-hoc analysis of the TOPCAT and HF-ACTION trials. The effect of AF on KCCQ overall summary scores (OSS), in both trials, was examined using a mixed effects regression model. Patients were divided into 3 groups according to AF status at baseline: patients with a history of AF but no AF detected on ECG at enrollment (Hx AF group), patients with history of AF and AF detected on ECG at enrollment (ECG AF group) and patients with post-randomization new-onset AF (New AF group). ResultsIn TOPCAT, among 1710 patients with KCCQ data available, AF was associated with a significantly lower KCCQ-OSS (-3.98; 95% CI -7.21: -0.74) at 48 months, with a significant AF status by time interaction (p=0.03). In HF-ACTION, among 1814 patients with available KCCQ data, AF was associated with a significantly lower KCCQ-OSS (-3.67; 95% CI -6.21: -1.41) at 24 months but there was no significant AF status by time interaction. In both trials, the type of AF was not associated with significant changes in KCCQ-OSS score. ConclusionΙn patients with both HFpEF and HFrEF, AF was independently associated with worse HRQoL measured by KCCQ.

Segment selection for fusion and artificial disc replacement in the hybrid surgical treatment of noncontiguous cervical spondylosis: a finite element analysis.

Introduction: The treatment of skip-level cervical degenerative disease (CDD) with no degenerative changes observed in the intervening segment (IS) is complicated. This research aims to provide a reference basis for selecting treatment approaches for noncontiguous CDD. Methods: To establish accurate finite element models (FEMs), this study included computed tomography (CT) data from 21 patients with CDD (10 males and 11 females) for modeling. The study primarily discusses four cross-segment surgical approaches: upper (C3/4) anterior cervical discectomy and fusion (ACDF) and lower (C5/6) cervical disc arthroplasty (CDA), FA model; upper CDA (C3/4) and lower ACDF (C5/6), AF model; upper ACDF (C3/4) and lower ACDF (C5/6), FF model; upper CDA (C3/4) and lower CDA (C5/6), AA model. An initial axial load of 73.6 N was applied at the motion center using the follower load technique. A moment of 1.0Nm was applied at the center of the C2 vertebra to simulate the overall motion of the model. The statistical analysis was conducted using STATA version 14.0. Statistical significance was defined as a p value less than 0.05. Results: The AA group had significantly greater ROM in flexion and axial rotation in other segments compared to the FA group (p < 0.05). The FA group consistently exhibited higher average intervertebral disc pressure in C2/3 during all motions compared to the AF group (p < 0.001); however, the FA group displayed lower average intervertebral disc pressure in C6/7 during all motions (p < 0.05). The AA group had lower facet joint contact stresses during extension in all segments compared to the AF group (p < 0.05). The FA group exhibited significantly higher facet joint contact stresses during extension in C2/3 (p < 0.001) and C6/7 (p < 0.001) compared to the AF group. Discussion: The use of skip-level CDA is recommended for the treatment of non-contiguous CDD. The FA construct shows superior biomechanical performance compared to the AF construct.

Influence of fentanyl, medetomidine-fentanyl or acepromazine-fentanyl premedication on oesophageal and rectal temperature in dogs under anaesthesia

ObjectiveTo compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine–fentanyl or acepromazine–fentanyl. Study designProspective, randomized, blind clinical study. AnimalsA total of 120 healthy dogs, aged 2–10 years and weighing 5–20 kg. MethodsDogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg–1), MF group with medetomidine (0.005 mg kg–1) and fentanyl (0.01 mg kg–1) and AF group with acepromazine (0.01 mg kg–1) and fentanyl (0.01 mg kg–1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen–air mixture. Fentanyl was administered continuously (0.01 mg kg–1 hour–1). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10–T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05). ResultsMedian T-Oeso was significantly higher in MF group between T0–T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60). Conclusions and clinical relevancePremedication with fentanyl, medetomidine–fentanyl or acepromazine–fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine–fentanyl. However, this difference was not clinically significant.

Association of lipopolysaccharide with new-onset atrial fibrillation in ST-segment elevation myocardial infarction

BackgroundLipopolysaccharide (LPS) is related to various cardiovascular diseases. However, the relationship between LPS and new-onset atrial fibrillation (NOAF) after ST-segment elevation myocardial infarction (STEMI) has yet to be elucidated. This study aimed to evaluate the impact of LPS on NOAF in STEMI patients. MethodsThis was a single-center retrospective observational study including 806 patients diagnosed with STEMI. LPS levels were determined using a commercial ELISA kit. NOAF was characterized by postadmission AF with the absence of any prior history of AF. ResultsA total of 806 participants were enrolled, with 752 individuals in the non-AF group (93.3%) and 54 individuals in the AF group (6.7%). Multivariable analysis showed that LPS (OR = 1.047; 95% CI: 1.029–1.065, P < 0.001) was an independent risk marker for NOAF. The analysis of the ROC demonstrated that LPS had an AUC of 0.717 in predicting NOAF. When LPS was added to the conventional model, the ability of the risk model to discriminate and reclassify NOAF was improved significantly (IDI 0.053, P = 0.001; NRI 0.510, P < 0.001). ConclusionElevated LPS is associated with an increased risk of NOAF in STEMI patients. The integration of LPS can improve the ability to predict NOAF in STEMI patients.