Milvexian: An Oral, Bioavailable Factor XIa Inhibitor.

Direct oral anticoagulants have a dose-dependent increased bleeding risk which limits use in certain populations. Studies in both animals and humans with inherited variations in factor XI levels provide a theoretical basis for a drug target capable of addressing current unmet needs. Milvexian is an oral factor XIa inhibitor that has the potential to provide robust anticoagulant effect without increased bleeding compared with current standard of care. Several key studies in the preclinical, phase I, and phase II stages have reported promising safety data in venous thromboembolism and stroke prevention without compromising hemostasis. The planned phase III trials will examine the efficacy of milvexian for prevention of thrombotic events in patients with acute stroke, acute coronary syndrome, and atrial fibrillation.

Artificial Intelligence in Cardiovascular Disease Prevention: Is it Ready for Prime Time?

PURPOSE OF REVIEW: This review evaluates how Artificial Intelligence (AI) enhances atherosclerotic cardiovascular disease (ASCVD) risk assessment, allows for opportunistic screening, and improves adherence to guidelines through the analysis of unstructured clinical data and patient-generated data. Additionally, it discusses strategies for integrating AI into clinical practice in preventive cardiology. RECENT FINDINGS: AI models have shown superior performance in personalized ASCVD risk evaluations compared to traditional risk scores. These models now support automated detection of ASCVD risk markers, including coronary artery calcium (CAC), across various imaging modalities such as dedicated ECG-gated CT scans, chest X-rays, mammograms, coronary angiography, and non-gated chest CT scans. Moreover, large language model (LLM) pipelines are effective in identifying and addressing gaps and disparities in ASCVD preventive care, and can also enhance patient education. AI applications are proving invaluable in preventing and managing ASCVD and are primed for clinical use, provided they are implemented within well-regulated, iterative clinical pathways.

Measurement and Application of Incidentally Detected Coronary Calcium: JACC Review Topic of the Week.

Coronary artery calcium (CAC) scoring is a powerful tool for atherosclerotic cardiovascular disease risk stratification. The nongated, noncontrast chest computed tomography scan (NCCT) has emerged as a source of CAC characterization with tremendous potential due to the high volume of NCCT scans. Application of incidental CAC characterization from NCCT has raised questions around score accuracy, standardization of methodology including the possibility of deep learning to automate the process, and the risk stratification potential of an NCCT-derived score. In this review, the authors aim to summarize the role of NCCT-derived CAC in preventive cardiovascular health today as well as explore future avenues for eventual clinical applicability in specific patient populations and broader health systems.

Frailty Status Modifies the Efficacy of ICD Therapy for Primary Prevention Among Patients With HF.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is recommended to reduce mortality risk in patients with heart failure with reduced ejection fraction (HFrEF). Frailty is common among patients with HFrEF and is associated with increased mortality risk. Whether the therapeutic efficacy of ICD is consistent among frail and nonfrail patients with HFrEF remains unclear. OBJECTIVES: The aim of this study was to evaluate the effect modification of baseline frailty burden on ICD efficacy for primary prevention among participants of the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). METHODS: Participants in SCD-HeFT with HFrEF randomized to ICD vs placebo were included. Baseline frailty was estimated using the Rockwood Frailty Index (FI), and participants were stratified into high (FI > median) vs low (FI ≤ median) frailty burden groups. Multivariable Cox models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether baseline frailty status modified the treatment effect of ICD for all-cause mortality. RESULTS: The study included 1,676 participants (mean age: 59 ± 12 years, 23% women) with a median FI of 0.30 (IQR: 0.23-0.37) in the low frailty group and 0.54 (IQR: 0.47-0.60) in the high frailty group. In adjusted Cox models, baseline frailty status significantly modified the treatment effect of ICD therapy (Pinteraction = 0.047). In separate stratified analysis by frailty status, ICD therapy was associated with a lower risk of all-cause mortality among participants with low frailty burden (HR: 0.56; 95% CI: 0.40-0.78) but not among those with high frailty burden (HR: 0.86; 95% CI: 0.68-1.09). CONCLUSIONS: Baseline frailty modified the efficacy of ICD therapy with a significant mortality benefit observed among participants with HFrEF and a low frailty burden but not among those with a high frailty burden.

Risk-adjusted analysis of perioperative outcomes after the Sistrunk procedure.

Objectives: Thyroglossal duct cyst (TGDC) is the most common pediatric congenital neck mass. The Sistrunk procedure is the standard method of excision and is associated with low rates of recurrence. This study aimed to review our institution's outcomes following the Sistrunk procedure, specifically the rates of wound complications and cyst recurrence. Methods: This was a retrospective case series of pediatric patients undergoing the Sistrunk procedure from June 2009 to April 2021. Results: A total of 273 patients were included. Of these, 139 (53%) patients were male and 181 (66%) were white. The average age at the time of surgery was 7.1 years. The overall cyst recurrence rate was 11%. The most common wound complications were seroma (14%) and surgical site infections (SSIs) (12%). Wound complications were associated with prior history of cyst infection (odds ratio [OR] 1.97, 95% confidence interval [CI] 1.07-3.60, z-test 2.2, p = .03). Pediatric surgery was associated with fewer wound complications (OR 0.18; 95% CI 0.05-0.6, z-test -2.78, p = .005). However, pediatric surgery operated on fewer patients with a history of cyst infection (36% vs. 55%, p = .012). Drain placement and postoperative antibiotics did not affect rates of wound complications. Conclusions: Prior cyst infection is associated with increased rates of postoperative wound complications. Postoperative antibiotics and drain placement did not significantly affect complication rates. Level of Evidence: 4.

The Role of Fecal Microbiota Transplantation in the Induction of Remission in Ulcerative Colitis.

BACKGROUND: Considerable research supports an important role for the microbiome and/or microbiome-host immune system interactions in the pathogenesis of inflammatory bowel disease (IBD). Consequently, microbiota-modulating interventions, such as fecal microbiota transplantation (FMT), have attracted interest in the management of IBD, including ulcerative colitis (UC). SUMMARY: While the clinical response to FMT in UC has varied between different studies, results to date may offer guidance toward optimal use of FMT. Thus, increased microbiome biodiversity, the presence of short-chain fatty acid-producing bacteria, Clostridium clusters IV and XIVa, Odoribacter splanchnicus, and reduced levels of Caudovirales bacteriophages have been identified as characteristics of the donor microbiome that predict a positive response. However, inconsistency in FMT protocol between studies confounds their interpretation, so it is currently difficult to predict response and premature to recommend FMT, in general, as a treatment for UC. Additional randomized controlled trials designed based on previous findings and employing a standardized protocol are needed to define the role of FMT in the management of UC. KEY MESSAGES: There is a well-developed rationale for the use of microbiome-modulating interventions in UC. Despite variations in study protocol and limitations in study design that confound their interpretation, FMT seems to benefit patients with UC, overall. Available data identify factors predicting FMT response and should lead to the development of optimal FMT study protocols.

Open Versus Minimally Invasive Approach for Craniosynostosis: Analysis of the National Surgical Quality Improvement Program-Pediatric.

OBJECTIVE: This multicenter study aimed to compare demographic, operative, and short-term outcomes data between open and minimally invasive surgical approaches for craniosynostosis repair utilizing the American College of Surgeon's National Surgical Quality Improvement Program Pediatric (NSQIP-P) database and highlight surgical disparities among races and ethnicities. DESIGN: Retrospective review of large multicenter database. SETTING: Freestanding general acute care children's hospitals, children's hospitals within a larger hospital, specialty children's hospitals, or general acute care hospitals with a pediatric wing. PATIENTS AND PARTICIPANTS: A total of 4931 pediatric patients underwent craniosynostosis correction within the NSQIP-P database from 2013 to 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Demographic information included age at surgery, sex, race, and ethnicity. Operative and outcomes measures included operative time, anesthesia time, days until discharge, postoperative complications, blood transfusions, 30-day readmission, and 30-day unplanned return to operating room. RESULTS: Patients who underwent minimally invasive surgery had significantly shorter operative and anesthesia times (p < .001; p < .001), fewer days until discharge (p < .001), fewer postoperative complications (p < .05), and less blood transfusions (p < .001). The proportion of White patients was significantly higher in the minimally invasive surgery group (p < .01), whereas Black and Hispanic patients had a significantly higher proportion in the open surgery group (p < .001; p < .001). Additionally, the percentage of patients undergoing minimally invasive surgery increased from 3.8% in 2014 to over 13% in 2019. CONCLUSIONS: This study adds to a growing consensus that minimally invasive surgery has significantly decreased operative time, anesthesia time, transfusion rates, length of hospital stay, and postoperative complications compared to open surgery. Racial and ethnic surgical disparities showed larger proportions of Black and Hispanic populations undergoing open procedures.

Use of Optical Coherence Tomography (OCT) in Assessment of Diabetic Skin Wound Characteristics and Blood Flow.

Optical coherence tomography allows for various measurements of skin but the utility of the device in determining properties of normal and wounded skin in diabetic patients is unknown. This single-site, non-randomized, observational study used an optical coherence tomography device to acquire skin images at 1305 nm, creating real-time image of 17 patient's skin and wounds 1 to 2 mm under the skin surface. Vertical B-scan, en-face and 3-D images were produced to calculate surface and dermal-epidermal junction roughness, the optical attenuation coefficient, a measure of light absorption and scattering, and blood flow metrics. In subjects with diabetes there was an increase in both the Ra (p < .02) and Rz (p < .001) of the wounded versus the control skin. In subjects without diabetes, there was an increase in both the Ra (p < .001) and Rz (p < .03) values of the wounded versus the control skin. At a depth of 0.6 mm across all subjects, there was an average decrease in blood flow of 63% from control to wounded skin. In subjects with diabetes, this decrease was 76%. In subjects without diabetes the decrease was 55%. The change in vasculature between control and wounded skin was associated with a p < .005. There was an increase in the Ra and Rz values and a decrease in blood flow between the wounded skin and control. The device determined a difference in the Ra and Rz values of both diabetic and healthy subjects' skin and a more pronounced decrease in blood flow in the wounds of patients with diabetes as opposed to those without.

Pediatric Tissue Expansion: Analysis of the National Surgical Quality Improvement Program-Pediatric.

INTRODUCTION: Tissue expansion (TE) in pediatric surgery provides vascularized tissue to attain functional and esthetic goals in a broad range of reconstructive procedures. Our study evaluates the demographic, operative, and short-term outcomes of TE in pediatric patients utilizing the American College of Surgeons National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database and highlights factors associated with postoperative complications. MATERIALS AND METHODS: Retrospective review of a large multicenter database of 402 pediatric patients that underwent TE within the NSQIP-P database from 2013 to 2020 at freestanding general acute care children's hospitals, children's hospitals within a larger hospital, specialty children's hospitals, or general acute care hospitals with a pediatric wing. Patient demographics, clinical risk factors, operative information, and postoperative outcomes were collected with an odds ratio analysis of risk factors. RESULTS: Patients were majority female (55.5%), White (63.2%), and non-Hispanic (67.4%). The minority were born prematurely (11.9%) and had congenital malformations (16.7%). Complications occurred in 5.7%, unplanned readmission in 4.5%, and unplanned operation in 6.5% of patients. Complications lead to readmission in 2.5% and return to the operating room in 3.2% of patients. American Society of Anesthesiology (ASA) score III-IV, congenital malformations, >1-day hospital stay, and pulmonary, neurologic, and hematologic comorbidities were associated with the greatest increase in odds of complication. CONCLUSION: This study utilizes the NSQIP-P to provide a comprehensive multicenter view of pediatric patients undergoing TE. Increased understanding of risk factors for complications allows for guidance in patient selection and helps in achieving favorable surgical outcomes.

Evaluation and characterization of facial skin aging using optical coherence tomography.

OBJECTIVES: The skin aging exposome encompasses internal and external factors that contribute to clinical signs of facial aging. Aging skin can be characterized by distinctive features such as wrinkles, lentigines, elastosis, and roughness. Optical coherence tomography (OCT) is capable of noninvasively measuring skin characteristics. This study aimed to assess bilateral features using OCT to explore temporal skin changes among decades and potential changes in facial skin aging based on laterality. METHODS: A total of 97 subjects between 20 and 89 years old with Fitzpatrick skin types I to IV were enrolled. VivoSight, a Multi-Beam OCT system intended to gather topographical and histological images of skin, was used to scan the area inferolateral to the lateral canthus, bilaterally. Investigators compared characteristics of skin roughness, attenuation coefficient and blood flow across age groups and based on laterality to determine any differences. RESULTS: Only data from successful OCT scans were used. Seventy subjects, 10 from each specified decade, had successful bilateral scans and were thus included in the analysis. Chronological aging was characterized by significantly decreased dermal attenuation coefficient with increased age. Skin roughness measurements showed trends of increased roughness with age; however, no statistically significant changes were seen between groups. Qualitative differences amongst scans taken on right and left sides of the face showed no significance regarding roughness, density or blood flow at depths ranging from 0.05 to 0.5 mm. CONCLUSIONS: OCT is an effective method for evaluating changes in aging skin. Our results illustrate a decline in skin density with chronological age. Additionally, it was illustrated that structural change in the epidermis and dermis does occur, however on a microscopic scale, there are no significant differences based on laterality. OCT holds promise as a noninvasive technique for characterization of aging skin. Its utility and application in the clinical management and treatment of aged skin requires further research; however, the technology has potential to personalize therapies based on objective findings.

The Efficacy of Intense Pulsed Light as a Treatment for Benign Pigmented Lesions on the Dorsal Hand.

BACKGROUND: Intense pulsed light (IPL) is a noninvasive therapeutic option to treat benign pigmented lesions by targeting melanin. OBJECTIVE: The purpose of this study was to assess IPL as a treatment for benign pigmented dorsal hand lesions. MATERIALS AND METHODS: A total of fifteen subjects, 40 to 73 years old, received 3 monthly IPL treatments over the dorsal hands. Subjects followed up 1 and 3 months after treatment. At every visit, photographs were taken using the VISIA Complexion Analysis System (Canfield Scientific, Fairfield, NJ) and analyzed using the RBX Brown Spots Analysis algorithm. The Clinician Global Aesthetic Improvement Scale and Subject Global Aesthetic Improvement Scale were completed at both follow-up visits. RESULTS: A total of fifteen subjects completed all six visits. The number of brown spots decreased 9.26% ( p = .0004) and 7.52% ( p = .0132) at each follow-up visit. The mean brown intensity decreased 6.15% ( p = .0183) and 7.67% ( p = .0178), whereas the mean contrast intensity decreased 8.88% ( p < .0001) and 6.60% ( p = .0007) 1 and 3 months after treatment, respectively. The mean Clinician Global Aesthetic Improvement Scale was 2.03 and 2.23, whereas the mean Subject Global Aesthetic Improvement Scale 1 and 3 months after treatment was 1.6 and 1.8, respectively. CONCLUSION: Objective analysis, along with clinician and subject assessments, showed an improvement in the appearance of benign pigmented lesions in the treated area after 3 IPL treatments.

Temporal and Spatial Assessment of the Corneal Response to UV Cross-Linking Using 3-Dimensional In Vivo Confocal Microscopy.

ABSTRACT: The goal of this study was to evaluate the temporal and spatial pattern of wound healing following UV corneal cross-linking (CXL) using 3-dimensional (3-D) confocal imaging in vivo. Using a modified Heidelberg Retinal Tomograph with Rostock Corneal Module confocal microscope, we performed 3-D scans on two patients at multiple time points after CXL. Patient 1 showed a normal post-CXL wound healing response, with initial subbasal nerve loss and keratocyte apoptosis in the anterior stroma, followed by partial restoration of both the nerve plexus and stromal keratocytes by 6 months. In patient 2, in addition to anterior corneal damage, pyknotic nuclei were observed in the posterior stroma 7 days after CXL. Acellular areas were present in the posterior stroma at 3 months, with only partial keratocyte repopulation at 6 months. Regeneration of the subbasal nerve plexus was also delayed. Three-dimensional confocal imaging allowed these unusual wound healing responses to be identified in the absence of any corresponding clinical observations.

Current and Future Photography Techniques in Aesthetic Surgery.

BACKGROUND: The rapidly increasing modalities and mediums of clinical photography, use of 3-dimensional (3D) and 4-dimensional (4D) patient modeling, and widening implementation of cloud-based storage and artificial intelligence (AI) call for an overview of various methods currently in use as well as future considerations in the field. OBJECTIVES: Through a close look at the methods used in aesthetic surgery photography, clinicians will be able to select the modality best suited to their practice and goals. METHODS: Review and discussion of current data pertaining to: 2-dimensional (2D) and 3D clinical photography, current photography software, augmented reality reconstruction, AI photography, and cloud-based storage. RESULTS: Important considerations for current image capture include a device with a gridded viewing screen and high megapixel resolution, a tripod with leveling base, studio lighting with dual-sourced light, standardized matte finish background, and consistency in patient orientation. Currently, 3D and 4D photography devices offer advantages such as improved communication to the patient on outcome expectation and better quality of patient service and safety. AI may contribute to post-capture processing and 3D printing of postoperative outcomes. Current smartphones distort patient perceptions about their appearance and should be used cautiously in an aesthetic surgery setting. Cloud-based storage provides flexibility, cost, and ease of service while remaining vulnerable to data breaches. CONCLUSIONS: While there are advancements to be made in the physical equipment and preparation for the photograph, the future of clinical photography will be heavily influenced by innovations in software and 3D and 4D modeling of outcomes.

Scattering angle resolved optical coherence tomography measures morphological changes in Bacillus subtilis colonies.

Significance: An unmet need is recognized for early detection and diagnosis of neurological diseases. Many psychological markers emerge years after disease onset. Mitochondrial dysfunction and corresponding neurodegeneration occur before onset of large-scale cell and tissue pathology. Early detection of subcellular morphology changes could serve as a beacon for early detection of neurological diseases. This study is on bacterial colonies, Bacillus subtilis, which are similar in size to mitochondria. Aim: This study investigates whether morphological changes can be detected in Bacillus subtilis using scattering angle resolved optical coherence tomography (SAR-OCT). Approach: The SAR-OCT was applied to detect scattering angle distribution changes in Bacillus subtilis. The rod-to-coccus shape transition of the bacteria was imaged, and the backscattering angle was analyzed by recording the distribution of the ratio of low- to medium angle scattering (L/M ratio). Bacillus orientation at different locations in colonies was analytically modeled and compared with SAR-OCT results. Results: Significant differences in the distribution of backscattering angle were observed in Bacillus subtilis transitioning from rod-to-coccus shapes. In Bacillus subtilis, the C -parameter of the Burr distribution of the SAR-OCT-derived L/M ratio was significantly smaller in coccus compared with rod-shaped bacteria. SAR-OCT-derived L/M ratio varied with bacterial position in the colony and is consistent with predicted orientations from previous studies. Conclusions: Study results support the potential of utilizing SAR-OCT to detect bacterial morphological changes.

Bipolar Fractional Radiofrequency Treatment of Suprapatellar Skin Assessment Using Noninvasive Devices and Microbiopsy.

BACKGROUND: Noninvasive treatments for skin tightening are gaining popularity. However, no studies have assessed bipolar fractional radiofrequency treatment on suprapatellar skin. OBJECTIVES: The purpose of this study was to evaluate the efficacy of bipolar fractional radiofrequency treatment on suprapatellar skin. METHODS: Twenty patients received 1 bilateral suprapatellar bipolar fractional radiofrequency treatment. They returned 7 days, 3 weeks, 3 months, and 6 months posttreatment. Noninvasive measurements were obtained at each visit, including high-resolution ultrasonography, optical coherence tomography, transepidermal water loss and skin elasticity. Microbiopsies were collected in the treatment area for histologic and gene expression analyses. Three clinicians completed photographic evaluations comparing texture and laxity at baseline vs 6 months posttreatment. RESULTS: Fifteen subjects completed all 6 visits. Both transepidermal water loss and dermal-epidermal junction roughness were increased at 3 weeks and 3 months posttreatment. Both attenuation coefficient and stiffness were increased significantly at 3 and 6 months posttreatment. Blood flow 0.5 mm below the surface and expression of epidermal hyaluronic acid and inflammatory genes IL-1b and IL-6 were significantly higher at 7 days posttreatment compared with pretreatment and 3 months posttreatment. There were no statistically significant changes in collagen- or elastin-related genes and proteins at 7 days or 3 months posttreatment. An improvement in texture and laxity was observed at 6 months posttreatment in 17.7% and 24.4% of photographs, respectively. CONCLUSIONS: Radiofrequency treatment by microneedling of suprapatellar skin shows limited effects in decreasing skin laxity and improving skin appearance. At a molecular level, the treatment resulted in lower elastin and hyaluronic acid levels and increased dermal-epidermal junction roughness based on histology and optical coherence tomography imaging.