The Influence of Tacrolimus on Cellular Morphology, Cellular Viability, Osteogenic Differentiation, and mRNA Expression within Stem Cell Spheroids.

Background and Objectives: Tacrolimus is a macrolide lactone compound derived from the bacterium Streptomyces tsukubensis, widely known as an immunosuppressant. In basic research, the effects of tacrolimus on osteogenic differentiation have been tested using mesenchymal stem cells. In this study, tacrolimus's effects on the cellular survival and osteogenic differentiation of stem cell spheroids were investigated. Materials and Methods: Concave microwells were used to form stem cell spheroids in the presence of tacrolimus at final concentrations of 0 µg/mL, 0.1 µg/mL, 1 µg/mL, 10 µg/mL, and 100 µg/mL. A microscope was used to test cellular vitality qualitatively, and an assay kit based on water-soluble tetrazolium salt was used to measure cellular viability quantitatively. Alkaline phosphatase activity and an anthraquinone dye test for measuring calcium deposits were used to assess osteogenic differentiation. To assess the expression of osteogenic differentiation, a quantitative polymerase chain reaction, Western blot, and RNA sequencing were performed. Results: Spheroids across all concentrations maintained a relatively uniform and spherical shape. Cell viability assay indicated that tacrolimus, up to a concentration of 100 µg/mL, did not significantly impair cell viability within spheroids cultured in osteogenic media. The increase in calcium deposition, particularly at lower concentrations of tacrolimus, points toward an enhancement in osteogenic differentiation. There was an increase in COL1A1 expression across all tacrolimus concentrations, as evidenced by the elevated mean and median values, which may indicate enhanced osteogenic activity. Conclusions: This study showed that tacrolimus does not significantly impact the viability of stem cell spheroids in osteogenic media, even at high concentrations. It also suggests that tacrolimus may enhance osteogenic differentiation, as indicated by increased calcium deposition and COL1A1 expression. These findings advance our understanding of tacrolimus's potential roles in tissue repair, regeneration, and stem cell-based therapeutic applications.

Toward Quantitative Electrodeposition via In Situ Liquid Phase Transmission Electron Microscopy: Studying Electroplated Zinc Using Basic Image Processing and 4D STEM.

High energy density electrochemical systems such as metal batteries suffer from uncontrollable dendrite growth on cycling, which can severely compromise battery safety and longevity. This originates from the thermodynamic preference of metal nucleation on electrode surfaces, where obtaining the crucial information on metal deposits in terms of crystal orientation, plated volume, and growth rate is very challenging. In situ liquid phase transmission electron microscopy (LPTEM) is a promising technique to visualize and understand electrodeposition processes, however a detailed quantification of which presents significant difficulties. Here by performing Zn electroplating and analyzing the data via basic image processing, this work not only sheds new light on the dendrite growth mechanism but also demonstrates a workflow showcasing how dendritic deposition can be visualized with volumetric and growth rate information. These results along with additionally corroborated 4D STEM analysis take steps to access information on the crystallographic orientation of the grown Zn nucleates and toward live quantification of in situ electrodeposition processes.

Association between body mass index and results of cryoballoon ablation in Korean patients with atrial fibrillation: an analysis from the Korean Heart Rhythm Society Cryoablation registry.

AIMS: Pulmonary vein isolation using cryoablation is effective and safe in patients with atrial fibrillation (AF). Although both obesity and underweight are associated with a higher risk for incident AF, there is limited data on the efficacy and safety following cryoablation according to body mass index (BMI) especially in Asians. METHODS AND RESULTS: Using the Korean Heart Rhythm Society Cryoablation registry, a multicentre registry of 12 tertiary hospitals, we analysed AF recurrence and procedure-related complications after cryoablation by BMI (kg/m2) groups (BMI < 18.5, underweight, UW; 18.5-23, normal, NW; 23-25, overweight, OW; 25-30, obese Ⅰ, OⅠ; ≥30, obese Ⅱ, OⅡ). A total of 2648 patients were included (median age 62.0 years; 76.7% men; 55.6% non-paroxysmal AF). Patients were categorized by BMI groups: 0.9% UW, 18.7% NW, 24.8% OW, 46.1% OI, and 9.4% OII. Underweight patients were the oldest and had least percentage of non-paroxysmal AF (33.3%). During a median follow-up of 1.7 years, atrial arrhythmia recurred in 874 (33.0%) patients (incidence rate, 18.9 per 100 person-years). After multivariable adjustment, the risk of AF recurrence was higher in UW group compared with NW group (adjusted hazard ratio, 95% confidence interval; 2.55, 1.18-5.50, P = 0.02). Procedure-related complications occurred in 123 (4.7%) patients, and the risk was higher for UW patients (odds ratio, 95% confidence interval; 2.90, 0.94-8.99, P = 0.07), mainly due to transient phrenic nerve palsy. CONCLUSION: Underweight patients showed a higher risk of AF recurrence after cryoablation compared with NW patients. Also, careful attention is needed on the occurrence of phrenic nerve palsy in UW patients.

Regeneration of Rabbit Calvarial Defects with Combination of Stem Cells and Enamel Matrix Derivative: A Microcomputed Tomography and Histological Evaluation Comparing Two- and Three-Dimensional Cell Constructs.

Background and Objectives: This study addresses the challenge of bone regeneration in calvarial defects, exploring the efficacy of stem cell-based therapies and enamel matrix derivative (EMD) in tissue engineering. It assesses the regenerative potential of two- and three-dimensional cell constructs combined with mesenchymal stem cells (MSCs) and EMD in rabbit calvarial defects. Materials and Methods: This research involved the use of bone-marrow-derived MSCs cultured in silicon elastomer-based concave microwells to form spheroids. White rabbits were grouped for different treatments, with Group 1 as control, Group 2 receiving only EMD, Group 3 getting EMD plus stem cells, and Group 4 being treated with EMD plus stem cell spheroids. Computed tomography (CT) and microcomputed tomography (micro-CT) imaging were used for structural assessment, while histological evaluations were conducted using hematoxylin and eosin, Masson's trichrome, and Picro-sirius red staining. Results: CT and micro-CT analyses revealed varying degrees of bone regeneration among the groups. Group 4, treated with three-dimensional MSC spheroids and EMD, showed the most significant improvement in bone regeneration. Histological analyses corroborated these findings, with Group 4 displaying enhanced bone formation and better collagen fiber organization. Conclusions: The study supported the biocompatibility and potential efficacy of three-dimensional MSC constructs combined with EMD in bone regeneration. Further investigations are needed to confirm these findings and optimize treatment protocols.

Association Between Atrial Fibrillation Symptoms and Clinical Outcomes: A Prospective Multicenter Registry Study.

The presence of symptoms plays an important role in determining whether to focus on rhythm control or rate control when treating atrial fibrillation (AF). Previous comparative studies on the clinical outcomes of symptomatic and asymptomatic AF have yielded inconsistent results, and a link between AF symptoms and left atrial (LA) remodeling is not established. Patients selected from the COmparison study of Drugs for symptom control and complication prEvention of AF (CODE-AF) registry, which is a prospective, multicenter study consisting of patients with non-valvular AF, were grouped into 2 groups: symptomatic and asymptomatic. The primary outcome was a composite of the following cardiovascular outcomes: all-cause death, ischemic stroke, transient ischemic attack, systemic embolism, myocardial infarction, and heart failure hospitalization. Of 10,210 patients with AF, 4,327 (42%) had symptomatic AF. The asymptomatic group had an older mean age, more men, and more patients with hypertension and diabetes mellitus than the symptomatic group. The asymptomatic group had a larger left atrium (LA) diameter (43.6 vs 42.2 mm, p <0.001) than the symptomatic group. During a median follow-up of 32.9 (29.5 to 36.4) months, the asymptomatic and symptomatic groups showed similar incidences of the primary outcome (1.44 vs 1.45 per 100 person-years; log-rank, p = 0.8). In conclusion, the absence of AF symptoms is associated with increased LA. However, symptomatic and asymptomatic patients with AF have a similar risk of cardiovascular outcomes. This suggests that beneficial treatment for AF may be considered regardless of whether patients have symptomatic or asymptomatic AF.

The impact of early cryoballoon ablation on clinical outcome in patients with atrial fibrillation: From the Korean cryoballoon ablation registry.

INTRODUCTION: Influence of early atrial fibrillation (AF) ablation, particularly cryoballoon ablation (CBA), on clinical outcome during long-term follow-up has not been clarified. The objective was to determine whether an early CBA (diagnosis-to-ablation of ≤6 months) strategy could affect freedom from AF recurrence after index CBA. METHODS: The study included 2605 patients from Korean CBA registry data with follow-up >12 months after de novo CBA. The primary outcome was recurrence of atrial tachyarrhythmias (ATs) of ≥30-s after a 3-month blanking period. RESULTS: Compared to patients in early CBA group, patients in late CBA group had higher prevalence of diabetes, congestive heart failure, and chronic kidney disease, and higher mean CHA2 DS2 -VAS score. During mean follow-up of >21 months, ATs recurrence was detected in 839 (32.2%) patients. The early CBA group showed a significantly lower 2-year recurrence rate of ATs than the late CBA group (26.1% vs. 31.7%, p = 0.043). In subgroup analysis, the early CBA group showed significantly higher 1-year and 2-year freedom from ATs recurrence than the late CBA group only in paroxysmal atrial fibrillation (PAF) patients in overall and propensity score matched cohorts. Multivariate analysis showed that early CBA was an independent factor for preventing ATs recurrence in PAF (hazard ratio: 0.637; 95% confidence intervals: 0.412-0.984). CONCLUSION: Early CBA strategy, resulting in significantly lower ATs recurrence during 2-year follow-up after index CBA, might be considered as an initial rhythm control therapy in patients with paroxysmal AF.

Uncovering Nitrosyl Reactivity at N-Heterocyclic Carbene Center.

N-heterocyclic carbenes (NHCs) have garnered much attention due to their unique properties, such as strong σ-donating and π-accepting abilities, as well as their transition-metal-like reactivity toward small molecules. In 2015, we discovered that NHCs can react with nitric oxide (NO) gas to form radical adducts that resemble transition metal nitrosyl complexes. To elucidate the analogy between NHC and transition metal NO adducts, here we have undertaken a systematic investigation of the electron- and proton-transfer chemistry of [NHC-NO]⋅ (N-heterocyclic carbene nitric oxide radical) compounds. We have accessed a suite of compounds, comprised of [NHC-NO]+ , [NHC-NO]- , [NHC-NOH]0 , and [NHC-NHOH]+ species. In particular, [NHC-NO]- was isolated as potassium and lithium ion adducts. Most interestingly, a monomeric potassium [NHC-NO]- compound was isolated with the assistance of 18-crown-6, which is the first instance of a monomeric alkali N-oxyl compound to the best of our knowledge. Our results demonstrate that [NHC-NO]⋅ exhibits redox behavior broadly similar to metal nitrosyl complexes, which opens up more possibilities for utilizing NHCs to build on the known reactivity of metal complexes.

Construction of a risk scoring system using clinical factors and RYR2 polymorphisms for bleeding complications in patients on direct oral anticoagulants.

Introduction: Bleeding is one of the most undesirable complications of direct oral anticoagulants (DOACs). While the ryanodine receptor (RYR2) has been related to cardiac diseases, research on bleeding complications is lacking. This study aimed to elucidate the association between RYR2 and bleeding risk to develop the risk scoring system in patients treated with DOACs. Methods: This study was a retrospective analysis of prospectively collected samples. We selected ten SNPs within the RYR2 gene, and two models were constructed (Model I: demographic factors only, Model II: demographic and genetic factors) in multivariable analysis. Independent risk factors for bleeding were used to develop a risk scoring system. Results: A total of 447 patients were included, and 49 experienced either major bleeding or clinically relevant non-major bleeding. In Model I, patients using rivaroxaban and experiencing anemia exhibited an increased bleeding risk after adjusting for covariates. Upon incorporating genetic factors into Model I, a significant association with bleeding was also observed in cases of overdosing on DOACs and in patients with a creatinine clearance (CrCl) < 30 mL/min, in addition to rivaroxaban and anemia (Model II). Among genetic factors, RYR2 rs12594 GG, rs17682073 AA, rs3766871 GG, and rs6678625 T alleles were associated with bleeding complications. The area under the receiver operating characteristic curve (AUROC) of Model I was 0.670, whereas that of Model II increased to 0.803, demonstrating better performance with the inclusion of genetic factors. Using the significant variables in Model II, a risk scoring system was constructed. The predicted bleeding risks for scores of 0, 1-2, 3-4, 5-6, 7-8, and 9-10 points were 0%, 1.2%, 4.6%, 15.7%, 41.7%, and 73.3%, respectively. Conclusion: This study revealed an association between RYR2 and bleeding complications among patients taking DOACs and established a risk scoring system to support individualized DOAC treatment for these patients.

Clinical applicability of an artificial intelligence prediction algorithm for early prediction of non-persistent atrial fibrillation.

Background and aims: It is difficult to document atrial fibrillation (AF) on ECG in patients with non-persistent atrial fibrillation (non-PeAF). There is limited understanding of whether an AI prediction algorithm could predict the occurrence of non-PeAF from the information of normal sinus rhythm (SR) of a 12-lead ECG. This study aimed to derive a precise predictive AI model for screening non-PeAF using SR ECG within 4 weeks. Methods: This retrospective cohort study included patients aged 18 to 99 with SR ECG on 12-lead standard ECG (10 seconds) in Ewha Womans University Medical Center for 3 years. Data were preprocessed into three window periods (which are defined with the duration from SR to non-PeAF detection) - 1 week, 2 weeks, and 4 weeks from the AF detection prospectively. For experiments, we adopted a Residual Neural Network model based on 1D-CNN proposed in a previous study. We used 7,595 SR ECGs (extracted from 215,875 ECGs) with window periods of 1 week, 2 weeks, and 4 weeks for analysis. Results: The prediction algorithm showed an AUC of 0.862 and an F1-score of 0.84 in the 1:4 matched group of a 1-week window period. For the 1:4 matched group of a 2-week window period, it showed an AUC of 0.864 and an F1-score of 0.85. Finally, for the 1:4 matched group of a 4-week window period, it showed an AUC of 0.842 and an F1-score of 0.83. Conclusion: The AI prediction algorithm showed the possibility of risk stratification for early detection of non-PeAF. Moreover, this study showed that a short window period is also sufficient to detect non-PeAF.

Artificial intelligence-enhanced 12-lead electrocardiography for identifying atrial fibrillation during sinus rhythm (AIAFib) trial: protocol for a multicenter retrospective study.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia, contributing significantly to morbidity and mortality. In a previous study, we developed a deep neural network for predicting paroxysmal atrial fibrillation (PAF) during sinus rhythm (SR) using digital data from standard 12-lead electrocardiography (ECG). The primary aim of this study is to validate an existing artificial intelligence (AI)-enhanced ECG algorithm for predicting PAF in a multicenter tertiary hospital. The secondary objective is to investigate whether the AI-enhanced ECG is associated with AF-related clinical outcomes. Methods and analysis: We will conduct a retrospective cohort study of more than 50,000 12-lead ECGs from November 1, 2012, to December 31, 2021, at 10 Korean University Hospitals. Data will be collected from patient records, including baseline demographics, comorbidities, laboratory findings, echocardiographic findings, hospitalizations, and related procedural outcomes, such as AF ablation and mortality. De-identification of ECG data through data encryption and anonymization will be conducted and the data will be analyzed using the AI algorithm previously developed for AF prediction. An area under the receiver operating characteristic curve will be created to test and validate the datasets and assess the AI-enabled ECGs acquired during the sinus rhythm to determine whether AF is present. Kaplan-Meier survival functions will be used to estimate the time to hospitalization, AF-related procedure outcomes, and mortality, with log-rank tests to compare patients with low and high risk of AF by AI. Multivariate Cox proportional hazards regression will estimate the effect of AI-enhanced ECG multimorbidity on clinical outcomes after stratifying patients by AF probability by AI. Discussion: This study will advance PAF prediction based on AI-enhanced ECGs. This approach is a novel method for risk stratification and emphasizes shared decision-making for early detection and management of patients with newly diagnosed AF. The results may revolutionize PAF management and unveil the wider potential of AI in predicting and managing cardiovascular diseases. Ethics and dissemination: The study findings will be published in peer-reviewed publications and disseminated at national and international conferences and through social media. This study was approved by the institutional review boards of all participating university hospitals. Data extraction, storage, and management were approved by the data review committees of all institutions. Clinical Trial Registration: [cris.nih.go.kr], identifier (KCT0007881).

Change in Maxillary Sinus Mucosal Thickness in Patients with Preoperative Maxillary Sinus Mucosal Thickening as Assessed by Otolaryngologists: A Retrospective Study.

Background and Objectives: Maxillary sinus pathologic conditions may increase the risk of complications during posterior maxillary sinus augmentation surgery. The purpose of this study was to evaluate the changes in participants with preoperative maxillary sinus mucosal thickening and to assess this factor as a preoperative risk indicator for sinusitis after maxillary dental implantation. Materials and Methods: We compared the preoperative and postoperative maxillary sinus mucosal thickness (MSMT), the distance between the maxillary sinus ostium and sinus floor (MOD), and the MSMT/MOD ratio. The participants were divided into three groups (sinus augmentation, bone grafting, and no grafting). Results: The mean preoperative MSMT was 4.3 ± 2.0 mm, and the mean MSMT/MOD ratio was 0.13 ± 0.05. No postoperative sinusitis was observed in these patients, including cases caused by anatomical variations. The mean postoperative MSMT was 4.5 ± 2.3 mm, and the mean postoperative MSMT/MOD ratio was 0.15 ± 0.06. There was no statistically significant difference between the groups at each time point (p > 0.05). Conclusions: The study found no significant change in MSMT at post-treatment evaluation, even when considering different subgroups. It underscores the importance of preoperative maxillary sinus radiographic assessments and collaboration between dentists and otolaryngologists for better outcomes in patients with preoperative maxillary sinus mucosal thickening.

Comparative Efficacy of Traditional Corticotomy and Flapless Piezotomy in Facilitating Orthodontic Tooth Movement: A Systematic Review and Meta-Analysis.

Background and Objectives: This study aimed to perform a meta-analysis comparing the effects of corticotomy and flapless piezocision on accelerated tooth movement. Materials and Methods: A comprehensive search using a combination of controlled vocabulary (MeSH) and free-text terms was undertaken by two reviewers to identify published systematic reviews. Three major electronic databases (Medline via PubMed, Cochrane Database, and Embase) were searched up to 2 June 2023. Results: The results of the meta-analysis showed that the pooled standardized mean difference values of accumulative movement distances for flapless piezocision were 1.43 (95% CI, 0.38 to 2.48; p < 0.01), 1.09 (95% CI, -0.08 to 2.26; p = 0.07), and 0.73 (95% CI, -0.58 to 4.02; p = 0.14). The results of the meta-analysis demonstrated that the pooled SMD values of accumulative movement distances for the corticotomy were 2.76 (95% CI, 0.18 to 5.34; p = 0.04), 1.43 (95% CI, -1.10 to 3.96; p = 0.27), and 4.78 (95% CI, -4.54 to 14.10; p = 0.32). Although the test for overall effectiveness was significant for piezocision and corticotomy, there were no significant differences between piezocision and corticotomy. Conclusions: The study determined that both conventional corticotomy and flapless piezosurgery are effective as adjuncts to orthodontic treatment. Moreover, no significant difference was observed in the short-term effectiveness of canine retraction acceleration between conventional corticotomy and flapless piezocision. While piezocision may be a favorable option for orthodontic treatment, corticotomy can be considered in cases requiring additional procedures such as bone grafting.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Predicting Future Incidences of Cardiac Arrhythmias Using Discrete Heartbeats from Normal Sinus Rhythm ECG Signals via Deep Learning Methods.

This study aims to compare the effectiveness of using discrete heartbeats versus an entire 12-lead electrocardiogram (ECG) as the input for predicting future occurrences of arrhythmia and atrial fibrillation using deep learning models. Experiments were conducted using two types of inputs: a combination of discrete heartbeats extracted from 12-lead ECG and an entire 12-lead ECG signal of 10 s. This study utilized 326,904 ECG signals from 134,447 patients and categorized them into three groups: true-normal sinus rhythm (T-NSR), atrial fibrillation-normal sinus rhythm (AF-NSR), and clinically important arrhythmia-normal sinus rhythm (CIA-NSR). The T-NSR group comprised patients with at least three normal rhythms in a year and no atrial fibrillation or arrhythmias history. Clinically important arrhythmia included atrial fibrillation, atrial flutter, atrial premature contraction, atrial tachycardia, ventricular premature contraction, ventricular tachycardia, right and left bundle branch block, and atrioventricular block over the second degree. The AF-NSR group included normal sinus rhythm paired with atrial fibrillation or atrial flutter within 14 days, and the CIA-NSR group comprised normal sinus rhythm paired with CIA occurring within 14 days. Three deep learning models, ResNet-18, LSTM, and Transformer-based models, were utilized to distinguish T-NSR from AF-NSR and T-NSR from CIA-NSR. The experiments demonstrated the potential of using discrete heartbeats in predicting future arrhythmia and atrial fibrillation incidences extracted from 12-lead electrocardiogram (ECG) signals alone, without any additional patient information. The analysis reveals that these discrete heartbeats contain subtle patterns that deep learning models can identify. Focusing on discrete heartbeats may lead to more timely and accurate diagnoses of these conditions, improving patient outcomes and enabling automated diagnosis using ECG signals as a biomarker.

Decreased GCF DEL-1 and increased GCF neutrophils with increasing probing pocket depth.

PURPOSE: Developmental endothelial locus-1 (DEL-1) plays a role in regulating neutrophil migration within the periodontium. The objective of this study was to evaluate the levels of DEL-1 in saliva and gingival crevicular fluid (GCF), as well as the number of neutrophils in patients with periodontitis. METHODS: Forty systemically healthy, non-smoking periodontitis patients participated in this study. Clinical periodontal parameters, including the plaque index, probing pocket depth (PPD), clinical attachment level, bleeding on probing, modified sulcular bleeding index, and marginal bone level, were measured. Levels of DEL-1, interleukin (IL)-1ß, IL-6, and IL-8 in unstimulated saliva samples, as well as DEL-1 in the GCF of 3 teeth from each participant, were assessed. Neutrophil counts in oral rinse and GCF samples were recorded. Spearman correlation coefficients were used to examine the correlation between protein levels, clinical parameters, and neutrophil quantities. Participants were divided into 2 age groups (those under 50 years and those 50 years or older) in order to investigate potential age-related differences. RESULTS: DEL-1 levels in the GCF showed a negative relationship with PPD (sum). Neutrophils in oral rinse samples were positively correlated with PPD, IL-8, and IL-1ß levels. Neutrophils in GCF exhibited a positive correlation with PPD (sum). Salivary DEL-1 levels showed correlations with IL-8 and IL-1ß, but not with the clinical parameters of periodontitis. CONCLUSIONS: The negative relationship observed between PPD and GCF DEL-1 levels is consistent with the proposed protective role of DEL-1.

Effect of Infraorbital and/or Infratrochlear Nerve Blocks on Postoperative Care in Patients with Septorhinoplasty: A Meta-Analysis.

Background and Objectives: Through a comprehensive meta-analysis of the pertinent literature, this study evaluated the utility and efficacy of perioperative infraorbital and/or infratrochlear nerve blocks in reducing postoperative pain and related morbidities in patients undergoing septorhinoplasty. Materials and Methods: We reviewed studies retrieved from the PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to August 2023. The analysis included a selection of seven articles that compared a treatment group receiving perioperative infraorbital and/or infratrochlear nerve blocks with a control group that either received a placebo or no treatment. The evaluated outcomes covered parameters such as postoperative pain, the amount and frequency of analgesic medication administration, the incidence of postoperative nausea and vomiting, as well as the manifestation of emergence agitation. Results: The treatment group displayed a significant reduction in postoperative pain (mean difference = -1.7236 [-2.6825; -0.7646], I2 = 98.8%), as well as a significant decrease in both the amount (standardized mean difference = -2.4629 [-3.8042; -1.1216], I2 = 93.0%) and frequency (odds ratio = 0.3584 [0.1383; 0.9287], I2 = 59.7%) of analgesic medication use compared to the control. The incidence of emergence agitation (odds ratio = 0.2040 [0.0907; 0.4590], I2 = 0.0%) was notably lower in the treatment group. The incidence of postoperative nausea and vomiting (odds ratio = 0.5393 [0.1309; 2.2218], I2 = 60.4%) showed a trend towards reduction, although it was not statistically significant. While no adverse effects reaching statistical significance were reported in the analyzed studies, hematoma (proportional rate = 0.2133 [0.0905; 0.4250], I2 = 76.9%) and edema (proportional rate = 0.1935 [0.1048; 0.3296], I2 = 57.2%) after blocks appeared at rates of approximately 20%. Conclusions: Infraorbital and/or infratrochlear nerve blocks for septorhinoplasty effectively reduce postoperative pain and emergence agitation without notable adverse outcomes.

Association between SLCO1B1 genetic polymorphisms and bleeding risk in patients treated with edoxaban.

Since SLCO1B1 encodes the uptake transporter OATP1B1, which can influence the pharmacokinetic and pharmacodynamic profiles of edoxaban, polymorphisms in SLCO1B1 may affect the edoxaban response. This study aimed to investigate the association between SLCO1B1 gene polymorphisms and the bleeding risk in patients receiving edoxaban. We genotyped 10 single-nucleotide polymorphisms (SNPs) from the SLCO1B1 gene in patients receiving edoxaban. We also analyzed rs3842 of ABCB1 as a confounder. The odds ratio (OR) and adjusted OR (AOR) were calculated from univariate and multivariable analysis, respectively. The area under the receiver operating characteristic curve (AUROC) was constructed for the discrimination of the model. A total of 159 patients receiving edoxaban were analyzed. Overdose and rs4149056 showed significant association with bleeding complications by around 11- and 5.5-fold, respectively. Additionally, patients with the rs4149057 variant allele (C) had a 3.9-fold increased bleeding risk compared with wild-type homozygote carriers (TT), whereas rs2306283 variant homozygote (GG) carriers had a 0.27-fold reduced bleeding risk compared with wild-type allele (A) carriers. Patients with the variant-type homozygote (CC) of ABCB1 rs3842 had a higher bleeding risk than T allele carriers (AOR = 5.3 and 5.9). The final models for multivariable analyses were acceptable based on the AUROC values (> 0.70). These findings may help predict bleeding risk in patients taking edoxaban and help personalize treatment.