Clinical Use Research Articles

Anti-Porphyromonas gingivalis Antibody Levels in Patients With Stroke and Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) and stroke are two highly related conditions, with periodontitis and periodontal pathogens, such as Porphyromonas gingivalis (Pg), appearing to be the most prominent common risk factors. In this study, we evaluated studies assessing Pg infection via serum/plasma anti-Pg antibodies in patients with AF and/or stroke. Online databases (PubMed, Scopus, Embase, and the Web of Science) were screened for studies showing the association between anti-Pg antibodies with stroke and/or AF. Relevant data were extracted, and a subsequent random-effects meta-analysis was performed to calculate the pooled odds ratio (OR) or standardized mean difference (SMD) and 95% confidence intervals (CIs) for Pg seropositivity or anti-Pg antibody levels in stroke patients compared to controls. Sixteen studies were included in the systematic review. Based on the meta-analysis performed, there was no significant difference in Pg IgA and IgG levels between patients with stroke and controls (IgA: SMD 0.11, 95% CI -0.02 to 0.25, p = 0.1; IgG: SMD -0.12, 95% CI -1.24 to 0.99, p = 0.83). Similarly, no difference was observed between these groups in terms of Pg IgA and IgG seropositivity (IgA: OR 1.63, 95% CI 1.06-2.50, p = 0.026; IgG: OR 2.30, 95% CI 1.39-3.78, p < 0.001). Subsequently, we reviewed the results of six articles investigating serum or plasma IgG antibodies against Pg in patients with AF. Our results revealed a strict association between Pg infection and AF, with AF patients exhibiting either higher anti-Pg antibody levels or a higher prevalence of positive serum Pg antibodies. Our study supports the clinical utility of Pg infection assessment in patients with periodontitis and those with AF and solicits more focused studies to corroborate its use in clinical settings to enhance overall outcomes, reduce the risk of complications like stroke, and help fine-tune personalized therapies.

Abstract 4138722: Large Language Model based multi-agent Transcatheter Aortic Valve Implantation team to augment multidisciplinary meetings - proof of concept.

Introduction: Multidisciplinary team (MDT) discussions are integral to Transcatheter Aortic Valve Implantation (TAVI) decision making. Large language model (LLM) ubiquity and low-code no-code platforms have enabled clinician lead solution development. Specialised chatbots or ‘agents’ have evolved into multi-agent systems that can personify human collaboration. We assess the performance of an artificial intelligence (AI) multi-agent TAVI MDT. Methods: Four de-identified TAVI cases from two metropolitan Australian hospitals were assessed by a mock human TAVI MDT (h-MDT) and an AI multi-agent TAVI MDT (ai-MDT). The ai-MDT was created with Agentflow within Flowise AITM and had a hierarchical multi-agent architecture suited to complex reasoning required for TAVI MDT simulation (figure). LLM limitations necessitated the ai-MDT rely on imaging reports rather than clinical images. The h-MDT and ai-MDT consisted of similar team members. Outputs from the h-MDT and ai-MDT was adjudicated by a panel of four blinded TAVI doctors that determined if output was human vs AI and assigned a SMIC score (4-12, 4=good, 12=poor) that assessed structure, missing information, incorrect information and clinical utility. Time durations for h-MDT and ai-MDT were recorded. Results: Adjudicators differentiated human vs. AI output 100% of the time and ai-MDT output had better SMIC scores than h-MDT (U-stat 213, p=0.0011). ai-MDT outperformed h-MDT in the domains of structure, missing information and clinical utility but was not statistically different in the incorrect information domain (U-stat 132, p=0.88). The average time for each case in h-MDT was 15 minutes and 45 seconds compared to 97 seconds for ai-MDT. Conclusion: This demonstrates the potential of using LLM based multi-agent systems as a clinical adjunct in highly specialized multidisciplinary clinical meetings. AI responses were superior for structure, clinical utility and missing information and non-inferior for incorrect information compared to humans, which highlights that hallucinations remain an issue with generative AI. Time was saved but image interpretation still requires human input, for now. Cognitive AI continues to require human supervision for implementation.

Clinical Tools to Assess Functional Capacity During Risk Assessment Before Elective Noncardiac Surgery : A Scoping Review.

Functional capacity is critical to preoperative risk assessment, yet guidance on its measurement in clinical practice remains lacking. To identify functional capacity assessment tools studied before surgery and characterize the extent of evidence regarding performance, including in populations where assessment is confounded by noncardiopulmonary reasons. MEDLINE, EMBASE, and EBM Reviews (until July 2024). Studies evaluating performance of functional capacity assessment tools administered before elective noncardiac surgery to stratify risk for postoperative outcomes. Study details, measurement properties, pragmatic qualities, and/or clinical utility metrics. 6 categories of performance-based tests and 5 approaches using patient-reported exercise tolerance were identified. Cardiopulmonary exercise testing (CPET) was the most studied tool (132 studies, 32 662 patients) followed by field walking tests (58 studies, 9393 patients) among performance-based tests. Among patient-reported assessments, the Duke Activity Status Index (14 studies, 3303 patients) and unstructured assessments (19 studies, 28 520 patients) were most researched. Most evidence focused on predictive validity (92% of studies), specifically accuracy in predicting cardiorespiratory complications. Several tools lacked evidence on reliability (test consistency across similar measurements), pragmatic qualities (feasibility of implementation), or concurrent criterion validity (correlation to gold standard). Only CPET had evidence on clinical utility (whether administration improved postoperative outcomes). Older adults (≥65 years) were well represented across studies, whereas there were minimal data in patients with obesity, lower-limb arthritis, and disability. Synthesis focused on reported data without requesting missing information. Though several tools for preoperative functional capacity assessment have been studied, research has overwhelmingly focused on CPET and only 1 aspect of validity (predictive validity). Important evidence gaps remain among vulnerable populations with obesity, arthritis, and physical disability. None. (Open Science Framework: https://osf.io/ah7u5).

Abstract 4140120: Artificial intelligence-driven morbidity prediction in acute kidney injury after acute type A aortic dissection surgery

Background: Acute kidney injury (AKI) often complicates acute type A aortic dissection (ATAAD), with elevated comorbidity rates and a significant tie to in-hospital mortality. Identifying risk factors early can mitigate AKI severity. Research Questions: This research endeavors to develop and corroborate predictive models leveraging Machine Learning (ML) techniques from Artificial Intelligence to forecast AKI occurrences in ATAAD-afflicted individuals. Methods: The study employed various machine learning (ML) algorithms including Gradient Boosting Machine (GBM), LightGBM, Random Forest (RF), K-Nearest Neighbors (KNN), Multi-Layer Perceptron Neural Network (MLP-NN), Naive Bayes (NB), Logistic Regression (LR), and ensemble methods (combining LR&amp;LightGBM), employing tenfold cross-validation. Model performance was evaluated using SHapley Additive exPlanations (SHAP). A web-based tool for predicting AKI incidence was developed using Streamlit, based on the most effective model. The analysis involved 1350 ATAAD patients, among whom 586 (43.4%) developed post-operative AKI. Patients were divided into two cohorts: 85% for training and 15% for testing, with 126 features included in the predictive model. Results: Incorporating top 10 features, LightGBM (AUROC=0.886, 95% CI 0.841-0.930) excelled in predictive accuracy, calibration, and clinical utility, identifying key factors such as ventilation time in ICU, hourly urine output post-surgery, diuretic use, Scr, heart rate, urea, administration of recombinant human brain natriuretic peptide and ebrantil, MCHC, and blood glucose as associated with ATAAD-AKI. Conclusion(s): These ML models are robust tools for predicting AKI in ATAAD patients, with LightGBM's superior predictive ability standing out. They offer valuable support for clinical decision-making in ATAAD management, helping optimize postoperative strategies to minimize AKI occurrence after surgery.

Abstract 4144583: Beyond Acute Rejection Screening Following Pediatric Heart Transplant: In Patients Negative for Rejection, Elevated Donor-Derived Cell-Free DNA is Associated with Cardiac Allograft Vasculopathy (CAV) and Donor Specific Antibodies (DSA)

Donor-derived cell-free DNA (dd-cfDNA) has been increasingly used to detect acute rejection (AR). We aimed to compare our institutional dd-cfDNA results to previously published adult and pediatric dd-cfDNA AR cutoffs. We also hypothesized that in the absence of AR, elevated dd-cfDNA would be associated with CAV and positive DSA. Patients (pt) &lt; 18 years at transplant with &gt; 1 dd-cfDNA between 2021-2023 were included. Using dd-cfDNA levels from this cohort, sensitivity, specificity, NPV, and PPV were calculated. False positives and false negatives (FN) were determined using published dd-cfDNA thresholds. AR was defined as decision-to-treat with increased immunosuppression, which was independent of dd-cfDNA in our cohort. In pt without AR, t -test was used to compare the means of dd-cfDNA levels in pt with and without DSA. χ 2 testing was then performed to evaluate the association between dd-cfDNA levels above and below 0.2% and the presence/absence of DSA and CAV. DSA was defined as allele-specific DSA identified by single antigen bead with mean fluorescence intensity &gt;1000, and CAV as any disease by angiography. There were 379 samples among 163 pt, a median of 2 samples per pt, and 32 samples obtained at time of AR. Performance of dd-cfDNA in our cohort vs published dd-cfDNA thresholds is shown in Table 1. The FN rate ranged from 16 to 37% as the dd-cfDNA threshold increased. Mean dd-cfDNA was higher in patients with positive DSA versus those without (0.83% vs 0.19%, p&lt;0.001). In patients that did not meet AR criteria, dd-cfDNA levels &gt; 0.2% were associated with a higher prevalence of positive DSA (n=66) (48% vs 13%, p&lt;0.001), and trended towards a higher prevalence of CAV (n=20) (15% vs 11%, p=0.08). Dd-cfDNA had high sensitivity and NPV for AR but the FN rate using published dd-cfDNA cutoffs was high in our validation cohort. The clinical utility of dd-cfDNA may extend beyond AR screening given increased frequency of DSA and CAV in pt with elevated levels that are negative for AR. We speculate that monitoring intra-pt dd-cfDNA variability will reduce the FN rate when screening for AR in addition to enhancing its clinical utility when monitoring for CAV and DSA.

Adjustable compression wraps: back to the future

Adjustable Compression Wraps (ACWs) are used to treat a variety of conditions, in particular venous leg ulcers, edema and lymphedema. Publications on the use of these devices are ultimately few and far between, with limitations or biases (small sample sizes, methodological weaknesses, non-comparative studies, lack of interface pressures). A development model like that used in the study of a drug could be more rational. We propose five phases: phase 1) discovery and development, phase 2) in vitro testing, phase 3) clinical trials, phase 4) real-life data analysis, medico-economic investigation using Artificial Intelligence (AI), and phase 5) preparation of regulatory dossiers. This lack of coherence in development could be an obstacle to widespread clinical use. Using AI to analyse large quantities of data could reduce the cost and number of clinical trials needed to generate more robust evidence. This would make it possible to better define the clinical effects of ACWs in specific situations (e.g., leg wounds in the elderly, diabetic wounds, mixed leg ulcers, secondary lymphedema of the upper limb, efficacy, and comfort...) and to compare treatment costs between bandages and ACWs. If we don't explore the future with AI, we'll never know what will be useful for the present - hence the title “Back to the Future”.

Indocyanine Green Marking of Axillary Sentinel Lymph Nodes in Early Breast Cancer

AbstractAxillary sentinel lymph node excision (SLNE) in breast cancer patients with clinically node-negative disease may be carried out using different tracers. The standard tracer is technetium colloid (99mTc). Indocyanine green (ICG) can be used as an alternative. This study aimed to evaluate the clinical usefulness of this fluorescent dye in a standardized setting.A prospective, single-center cohort study carried out at the University Gynecological Hospital of Rostock from September 2023 to May 2024 carried out sentinel lymph node marking using only ICG in patients with breast malignancies. The ICG injection was administered immediately after the induction of anesthesia. Detection of the sentinel lymph node (SLN) was done using a laparoscopy system suitable for ICG. The aim was to determine the detection rate (DR) for SLNs marked exclusively using ICG and to record any complications. The costs of using ICG to mark SLNs were compared with those for 99mTc marking.During the study period, contraindications against marking with ICG were ascertained for five (3.8%) of 132 patients with planned SLNE. A total of 100 SLNEs were carried out after ICG marking in patients who met the inclusion criteria in the context of the study. A median of two SLNs were resected. The detection rate (DR) for SLNs was 98.0%. SLNs were identified in all obese patients. No serious systemic side effects occurred following ICG injection. Transient skin discoloration in the area around the injection site were observed in eight patients. The direct cost of ICG marking was 62.73 Euros, which was 170.36 Euros lower than the cost of 99mTc marking.The detection rate of axillary SLNs marked using ICG is high and the method is cost-effective, has few side effects and can also be used in obese patients. Contraindications against the administration of ICG are rare. Marking with ICG is a good alternative to the 99mTc method and offers advantages in terms of costs, logistics, no exposure to radiation, and patient comfort.

Cone Beam Computed Tomography Evaluation of Socket Healing After Third Molar Germ Extraction: A Case Series Study Including Adolescents with Osteogenesis Imperfecta Type I Treated with Bisphosphonates and Healthy Age-Matched Subjects

Bisphophonates (BPs) are widely used in Osteogenesis imperfecta (OI). Cone Beam Computed Tomography (CBCT) shows clinical usefulness in evaluating impacted teeth and adjacent structure relationships, extraction socket healing, bone mineral density (BMD) and BP-related jaw osteonecrosis (BRONJ). The aim of the study was to compare alveolar sockets and the adjacent bone area before and after third molar extraction in OI type I (OI-I) adolescents treated with BPs and age-matched healthy subjects (HSs) by CBCT. Methods: Five adolescents with genetically proven OI-I treated with BPs (three males and two females, mean age: 15.2 ± 1.78 years) and four age-matched healthy subjects (two males and two females, mean age: 15.5 ± 1.29 years) were included in this study. Eight Regions of Interest (ROIs) were evaluated: between 3.7 and 3.8 (ROI-1) and 4.7 and 4.8 (ROI-2); after 3.8 (ROI-3) and 4.8 (ROI-4); alveolar sockets 3.8 (ROI-5) and 4.8 (ROI-6); left (ROI-7) and right (ROI-8) cortical bone. Results: ROIs were evaluated on both sides of the mandible for all the subjects except one OI patient in which CBCTs were performed pre- and-post third molar extraction only on the right side. CBCT was performed 12.8 ± 4.60 and 11.5 ± 2.51 days before and 8.0 ± 1.41 and 7.7 ± 0.5 months after extraction in OI-I and HSs, respectively. BPs were discontinued 62.0 ± 36.5 months before extraction. None of the OI-I adolescents developed BRONJ. Statistically significant greater values were observed in OI-I for ROI-1 and -2 (p = 0.0464), ROI-3 and -4 (p = 0.0037) and ROI-7 and -8 (p = 0.0079) after extraction. Conclusions: This descriptive study confirms that, in OI-I adolescents treated with BPs, third molar extraction is safe, and socket healing occurs properly. In addition, it demonstrates that, if the same device and imaging conditions are used and comparisons to predetermined standard values are avoided, CBCT can be used to monitor BMD changes. The significant greater BMD observed for different ROIs in OI-I could reflect the increased secondary mineralization related to the BP-dependent reduction in bone turnover.

Abstract 4135286: Comparative Efficacy of Intracardiac and Transesophageal Echocardiography in Left Atrial Appendage Occlusion: A Meta-Analysis of Clinical Outcomes

Background: Left atrial appendage occlusion (LAAO) is essential for stroke prevention in patients with non-valvular atrial fibrillation where anticoagulation is contraindicated. Intracardiac Echocardiography (ICE) has been proven effective and safe for LAAO since 2011, yet adoption rates remain low, with only 2.2% of LAAOs guided by ICE between 2015 and 2019. Transesophageal Echocardiography (TEE), the current gold standard, and ICE differ significantly in operational dynamics and patient impacts, influencing procedural outcomes. Objective: This study aims to compare the efficacy and safety of ICE and TEE in facilitating LAAO, offering insights into their comparative clinical use. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Searches were performed in MEDLINE/PubMed, OVID, and Scopus through December 2023, comparing ICE and TEE in LAAO. Inclusion criteria centered on studies reporting technical success, with secondary outcomes including length of stay (LOS), mortality, and adverse outcomes such as stroke, transient ischemic attacks (TIA), pericardial effusion, cardiac tamponade, device thrombosis, device embolization, and peri-device leaks. Data synthesis employed statistical methods utilizing R Studio. Results: Fourteen studies involving 4184 patients were included. The meta-analysis revealed no significant differences in technical success (OR 1.34, 95% CI: [0.76, 2.36]), LOS (OR 1.66, 95% CI: [0.80, 3.42]), or mortality (OR = 1.00, 95% CI: [0.50, 2.00]) between ICE and TEE. Similarly, non-significant differences were noted in stroke, TIA, pericardial effusion, and device leaks, with minimal heterogeneity (I 2 = 0%). Conclusion: ICE and TEE provide comparable clinical outcomes in LAAO, with no significant efficacy or safety differences. These results suggest that the choice between ICE and TEE should be based on procedural convenience, patient anatomy, and resource availability, rather than clinical outcomes alone. The equivalence in performance between these modalities allows for flexibility in clinical practice, ensuring that patient care can be customized to individual needs without compromising safety or effectiveness.

Automatic segmentation-based multi-modal radiomics analysis of US and MRI for predicting disease-free survival of breast cancer: a multicenter study.

Several studies have confirmed the potential value of applying radiomics to predict prognosis of breast cancer. However, the tumor segmentation in these studies depended on delineation or annotation of breast cancer by radiologist, which is often laborious, tedious, and vulnerable to inter- and intra-observer variability. Automatic segmentation is expected to overcome this difficulty. Herein, we aim to investigate the value of automatic segmentation-based multi-modal radiomics signature and magnetic resonance imaging (MRI) features in predicting disease-free survival (DFS) of patients diagnosed with invasive breast cancer. This retrospective multicenter study included a total of 643 female patients with invasive breast cancer who underwent preoperative ultrasound (US) and MRI for prognostic analysis. Data (n = 480) from center 1 were divided into training and internal testing sets, while data (n = 163) from centers 2 and 3 were analyzed as the external testing set. We developed automatic segmentation frameworks for tumor segmentation by deep learning. Then, Least absolute shrinkage and selection operator Cox regression was used to select features to construct radiomics signature, and corresponding radiomics score (Rad-score) was calculated. Finally, six models for predicting DFS were constructed by using Cox regression and assessed in terms of discrimination, calibration, and clinical usefulness. The multi-modal radiomics signature combining intra- and peri-tumoral radiomics signatures of US and MRI achieved a higher C-index in the internal (0.734) and external (0.708) testing sets than most other radiomics signatures in predicting DFS, and successfully stratified patients into low- and high-risk groups. The multi-modal clinical imaging model combining the multi-modal Rad-score and clinical traditional MRI model-score resulted in a higher C-index (0.795) than other models in the external testing set, and it had a better calibration and higher clinical benefit. This study demonstrates that the multi-modal radiomics signature derived from automatic segmentations of US and MRI is a promising risk stratification biomarker for breast cancer, and highlights that the appropriate combination of multi-modal radiomics signature, clinical characteristics, and MRI feature can improve performance of individualized DFS prediction, which might assist in guiding decision-making related to breast cancer.

Abstract 4134308: Re-evaluating the safety profile of Semaglutide: An updated meta-analysis

Background: Semaglutide is increasingly used in the management of type 2 diabetes mellitus and obesity. Ensuring safety of this medication is crucial for its clinical use. This meta-analysis evaluates the safety profile of semaglutide across patient populations and treatment durations. Methods: Randomized controlled trials assessing the safety of semaglutide versus placebo, with specified treatment durations were identified. The primary outcome was occurrence of any cardiovascular adverse events. Secondary outcomes included sudden cardiac death, adverse events leading to death, adverse events, gastrointestinal side effects, occurrence of hypoglycemia and new-onset neoplasm. Results: A total of 23 studies met the inclusion criteria with a combined sample size of 57,911 participants. The meta-analysis revealed that the adverse event associated with semaglutide is gastrointestinal in nature (nausea and vomiting). No significant differences were observed between semaglutide and comparator groups. (See Figure 1) Conclusion: Semaglutide appears to have a favorable safety profile across diverse patient populations and treatment durations, supporting its continued use in the management of type 2 diabetes mellitus and obesity. It is generally well-tolerated, with a low incidence of adverse events. Clinicians should be aware of these findings and monitor patients accordingly. Further long-term studies are warranted to assess the safety of semaglutide in clinical practice.

Towards the clinical translation of a silver sulfide nanoparticle contrast agent: large scale production with a highly parallelized microfluidic chip.

Ultrasmall silver sulfide nanoparticles (Ag2S-NP) have been identified as promising contrast agents for a number of modalities and in particular for dual-energy mammography. These Ag2S-NP have demonstrated marked advantages over clinically available agents with the ability to generate higher contrast with high biocompatibility. However, current synthesis methods for inorganic nanoparticles are low-throughput and highly time-intensive, limiting the possibility of large animal studies or eventual clinical use of this potential imaging agent. We herein report the use of a scalable silicon microfluidic system (SSMS) for the large-scale synthesis of Ag2S-NP. Ag2S-NP produced using this system were compared to bulk synthesis and a commercially available microfluidic device through characterization, contrast generation, in vivo imaging, and clearance profiles. Using SSMS chips with 1 channel, 10 parallelized channels, and 256 parallelized channels, we determined that the Ag2S-NP produced were of similar quality as measured by core size, concentration, UV-visible spectrometry, and in vitro contrast generation. Moreover, by combining parallelized chips with increasing reagent concentration, we were able to increase output by an overall factor of 5,100. We also found that in vivo imaging contrast generation was consistent across synthesis methods and confirmed renal clearance of the ultrasmall nanoparticles. Finally, we found best-in-class clearance of the Ag2S-NP occurred within 24h. These studies have identified a promising method for the large-scale production of Ag2S-NP, paving the way for eventual clinical translation.

Optimal hyperthermic intraperitoneal chemotherapy regimen for advanced and peritoneal metastatic gastric cancer: a systematic review and Bayesian network meta-analysis

BackgroundPeritoneal metastasis is one of the most common modes of spread of gastric cancer. Currently, surgical treatment combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and systemic chemotherapy has demonstrated promising outcomes in both the treatment and prevention of peritoneal metastasis in gastric cancer. However, various HIPEC drug regimens are in clinical use, and their efficacy remains unclear. This study aims to evaluate the effectiveness of different HIPEC drug regimens in patients with advanced gastric cancer to determine the optimal therapeutic approach.MethodsThis study conducted a systematic review and Bayesian network meta-analysis. Patients in the experimental group underwent surgery combined with HIPEC and chemotherapy. The search period covered literature from database inception to June 1, 2024. Hazard ratios (HRs) with 95% confidence intervals (CIs) were used to evaluate overall survival (OS) as the primary outcome. Odds ratios (ORs) with 95% CIs were used to assess overall disease recurrence, peritoneal recurrence, and postoperative morbidity as secondary outcomes. To ensure scientific rigor and transparency, this study has been registered with PROSPERO (CRD42024533948).ResultsA total of 11 randomized controlled trials (RCTs) involving 1092 patients were included. Compared to surgery combined with chemotherapy, the regimens of cisplatin (HRs = 0.52, 95% CI: 0.38-0.73), mitomycin C (HRs = 0.99, 95% CI: 0.55-1.79), cisplatin plus fluorouracil (HRs = 0.60, 95% CI: 0.38-0.95), and oxaliplatin plus 5-fluorouracil (HRs = 0.53, 95% CI: 0.36-0.78) all demonstrated benefits in OS. The cisplatin (ORs = 0.16, 95% CI: 0.03-0.60) and mitomycin C (ORs = 0.03, 95% CI: 0-0.71) regimens also showed advantages in reducing peritoneal recurrence, with no impact on postoperative morbidity. Importantly, the cisplatin regimen was superior to other regimens in terms of OS and overall disease recurrence, achieving a balance between efficacy and safety.ConclusionsCompared to chemotherapy alone, HIPEC treatment shows significant benefits in OS without a notable disadvantage in postoperative morbidity. Although no single HIPEC regimen demonstrated clear benefits across all outcomes, the cisplatin regimen performed well in multiple aspects, indicating its potential for further research and clinical application.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=533948, identifier CRD42024533948.

Association of hypertension defined by the 2017 ACC/AHA guideline and choroidal thickness changes in type 2 diabetes: a 2-year longitudinal study.

This prospective cohort study investigated the longitudinal relationship between hypertension (HTN), defined by the 2017 ACC/AHA guidelines, and changes in choroidal thickness (CT) in patients with type 2 diabetes. Patients aged 30-80 years from the Guangzhou Diabetic Eye Study were categorized into non-HTN, stage 1-HTN, and stage 2-HTN groups based on BP criteria. Macular and parapapillary CT were measured using swept-source optical coherence tomography (SS-OCT). Mixed linear regression models analysed CT decline rates over a median 2.1-year follow-up, adjusting for confounders. 803 diabetes patients were included. Both stage 1-HTN and stage 2-HTN groups showed significantly thinner macular and parapapillary CT compared to non-HTN (all P < 0.05). Stage 2-HTN correlated with reduced macular CT thinning (coef = -11.29 μm/year; 95% CI, -22.36 to -0.22; P = 0.046) after adjustment, but not in the parapapillary area (coef = -4.07 μm/year; 95% CI, -12.89 to 4.74; P = 0.365). Subgroup analyses indicated faster macular CT decline in stage 2-HTN among those <65 years old (coef = -20.31 μm/year; 95% CI, -35.67 to -4.95; P = 0.10), males (coef = -14.1 μm/year; 95% CI, -32.54 to -4.33; P = 0.004), BMI ≥ 25 kg/m2 (coef = -10.24 μm/year; 95% CI, -26.86 to -6.38; P = 0.007), HbA1c > 6.5% (coef = -8.91 μm/year; 95% CI, -13.49 to -4.68; P = 0.001), and diabetes duration <10 years (coef = -12.78 μm/year; 95% CI, -27.48 to -1.91; P = 0.008). Stage 2-HTN is associated with accelerated macular CT loss in diabetic patients, suggesting macular CT measurements could potentially serve as early indicators of systemic hypertension. Further research is needed to establish precise CT cutoff values for clinical use in detecting and monitoring hypertension-related ocular changes.

Abstract 4115642: Resonance Sonomanometry in an Early Prototype Device Effectively Measures Continuous, Noninvasive Blood Pressure

Background: Nearly half of American adults have hypertension; however, reliable, continuous, noninvasive blood pressure (BP) measurement (cNIBP) for inpatient and outpatient use is not currently available. This study evaluated a new method for cNIBP measurement called resonance sonomanometry (RSM). RSM derives blood pressure using first-principles physics, is applicable to any artery, and requires no calibration, blood vessel deformation, or dependence on demographic inputs. Methods: A prospective, observational feasibility study was undertaken to compare carotid artery BP measurements with a prototype ultrasound-based cNIBP device incorporating RSM, to arterial catheter BP measurements in the radial arteries of 60 test subjects. Catheter measurements were obtained from a distal peripheral artery (radial), oscillometric cuff from the brachial artery, and RSM was obtained from a central artery (carotid). This study was the first-in-human study for the RSM method in comparison to arterial catheters. Results: RSM-induced arterial resonance was observed in all tested subjects. For each of the subjects, the arterial resonant frequency increased with increasing BP during systole, and decreased with diastole (consistent with the cardiac cycle), as predicted by the physical model. RSM-derived BP traces were qualitatively similar to catheter data, exhibiting features such as the dicrotic notch. The RSM method yielded similar diastolic BP (DBP), but lower systolic BP (SBP) compared to the arterial catheter, likely due to expected peripheral pulse amplification. RSM DBP was not significantly different from the catheter (+1.5mmHg, p = 0.187), while BP cuff DBP was significantly different from the catheter (−4.3mmHg, p=0.002). There were significant differences in the catheter to RSM SBP (34.1 mmHg, p &lt; 0.01), consistent with the aforementioned expectations from a central-versus-peripheral continuous pressure measurement. Conclusions: RSM is a novel BP measurement technique that could enable cNIBP measurements with accuracy required in hospitals. While the data are promising, significant future work remains. The study was meant to test the RSM method, not the device or form factor. Consequently, the form factor will need to be improved prior to clinical use. The prototype was designed for manual operation; thus, future work will also be needed to enhance the ability of the device to autonomously locate and track the artery for ease of use.

Abstract 4143219: Pressure-Volume Analysis by Three-Dimensional Echocardiography: A Novel Method to Estimate Left Ventricular Efficiency

Background: Left ventricular (LV) efficiency is a key pathophysiological marker in heart failure (HF). LV pressure curve estimation and three-dimensional (3D) volumes via echocardiography allows for non-invasive pressure-volume (PV) analysis and calculation of an index of efficiency (Figure 1). Aim: Validate efficiency index by 3D echocardiography by comparing it to invasive measurements and efficiency derived from Positron Emission Tomography (PET) metabolism. Methods: Two experimental models were utilized - one with canines (n=21) and another with sheep (n=12). In canines, echocardiography provided 3D LV volumes and valve event timings. The pressure curve was estimated by adjusting the time axis of a reference pressure curve to the valve events and its amplitude to measured peak LV pressure, which in clinical practice would be approximated as systolic brachial cuff pressure. Invasive pressure was measured by micromanometer and volume by subendocardial piezoelectric crystals. Non-invasive and invasive efficiency indices, calculated as the ratio of stroke work to total mechanical energy (Figure 1), were compared during baseline, right ventricular pacing, aortic constriction and dobutamine infusion. Twelve sheep implanted with a pacemaker underwent 8 weeks of rapid dyssynchronous DDD pacing to induce dilated HF. LV efficiency index was calculated as in Figure 1, using measurements from a PV-catheter calibrated to end-diastolic volume by cardiac MRI, and compared to efficiency calculated as stroke work divided by total LV glucose metabolism via PET/CT. Recordings were performed during AAI and DDD pacing, at baseline (n=3) and following 8 weeks pacing-induced HF (n=12). Results: In canines, non-invasive and invasive efficiency indices showed excellent agreement (r=0.95, p&lt;0.0001; mean difference 0.4%, SD 3.4%) (Figure 2). In sheep, the efficiency index showed similar decline compared to efficiency by PET/CT after induction of HF and after switching from AAI to DDD pacing (p&lt;0.05 for all interventions). Overall correlation between the methods was moderate (r=0.67, p=0.0001) but excellent in animals with longitudinal data (r=0.89, p=0.0001) (Figure 3). Conclusions: Efficiency index by 3D echocardiography is accurate and reflects changes in efficiency measured by PET/CT. It may thus be of interest for clinical use.

Lactobacillus plantarum KAD protects against high-fat diet-induced hepatic complications in Swiss albino mice: Role of inflammation and gut integrity.

Hepatic complications are the major health issues associated with dietary intake of calorie saturated food e.g. high-fat diet (HFD). Recent studies have revealed the beneficial effects of probiotics in HFD fed mice with hepatic complications. Some probiotic Lactic acid bacteria (LAB) e.g. Lactobacillus plantarum have drawn our attention in managing hepatic complications. Here, we aim to elucidate the protective effects of L. plantarum KAD strain, isolated from ethnic fermented food 'Kinema' in HFD-fed mice as, a preventive approach. Eighteen Swiss albino mice were equally divided into 3 groups: Normal Diet (ND), negative control (HFD), and HFD-fed with oral L. plantarum KAD supplementation (LP). All the experimental groups were subjected to specific diet according to grouping for eight weeks. After completion of the regime, subjects were anesthetized and sacrificed. Organs, blood, and fecal samples were collected and stored appropriately. Physical indices, including body weight gain, organ co-efficients were calculated along with assessment of glycemic, lipidomic, hepatic, oxidative stress, inflammatory, and histological parameters. Gut microbiota analysis was performed using 16s V3-V4 fecal metagenomic profiling, and sequencing were done using Illumina Miseq system. Oral administration of L. plantarum KAD is found to significantly (p<0.05) restore metabolic health by normalizing glycemic, lipidomic, hepatic parameters, oxidative stress and inflammatory parameters. Moreover, LP group (7.08±0.52 mg/g) showed significantly (p<0.001) decreased hepatic triglyceride level compared to HFD group (20.07±1.32 mg/g). L. plantarum KAD improved the adipocytic, and colonic histomorphology with significantly better scoring pattern. LP group (1.83±0.41) showed a significantly (p<0.001) reduced hepatic score compared to negative control group (5.00±0.63), showing reduced hepatosteatosis, and immune infiltration. The strain modulated gut health by altering its microbial composition positively towards normalization. In conclusion, the results of the experiment suggest that prophylactic L. plantarum KAD administration has beneficial effects on the onset of HFD induced hepatic complications in mice. Further studies are needed, on this strain for its clinical use as dietary supplement.

Abstract 4118084: Targeting Monoamine Oxidase B in Dystrophic mdx Hearts Dampens Inflammation and Fibrosis

Background: Cardiomyopathy is a major cause of death for Duchenne muscular dystrophy (DMD) patients. Current treatments cannot prevent cardiac tissue remodeling. Oxidative stress, inflammation and fibrosis are early events in DMD, preceding heart dysfunction. Monoamine Oxidase B (MAOB), which forms H 2 O 2 by oxidizing amines, is overactivated in inflammatory conditions and overcomes cell antioxidant defenses, thus altering redox homeostasis and eliciting harmful effects. We showed that targeting MAOB with inhibitors (iMAOB) improves skeletal muscle function in dystrophic mice by lowering oxidative stress, and reduces inflammation in murine models of sepsis and arthritis by dampening NF-kB, a redox-sensitive transcription factor. Aim: We explore the therapeutic potential of iMAOB to alleviate cardiomyopathy using dystrophin-deficient mdx mice. We hypothesize that iMAOB treatment could dampen oxidative stress, inflammation and fibrosis in dystrophic mdx hearts by modulating the phenotype of cells that are crucial in cardiac remodeling. Methods: Three-month-old mdx mice, that already show signs of fibrosis but no cardiac dysfunction, were orally treated with iMAOB or vehicle for one month (n≥ 6). Heart ventricular mononucleated cells were obtained by enzymatic digestion. Myeloid, endothelial and fibroblast cells were isolated by cell sorting by FACS and analysed by RT-PCR. Oxidative stress, inflammation and fibrosis were measured in whole tissue by immunohistochemistry. Results: The expression of proinflammatory and profibrotic genes was markedly increased in myeloid [Interleukin (Il)-1b, Il-6, Tgf-b and Spp1, the gene coding for osteopontin], endothelial [Il-1b, Il-6, mmp2 and nos3] and cardiac fibroblast cells [Tgf-b, Spp1, Timp1 and Col1] isolated from mdx hearts, as compared to wild type mice. All these genes were significantly dampened by iMAOB treatment. In parallel, once again iMAOB treatment blunted the increase in oxidative stress, inflammation and fibrosis observed in mdx cardiac sections. Of notice, the differences were not linked to changes in the percentage of the various cell types, as they were unmodified amongst wild type, mdx and iMAOB-treated mdx hearts. Conclusions: We show that iMAOB can positively affect the phenotype of cells that are important in cardiac tissue remodeling. Our data suggest that iMAOB can be a viable therapeutic tool in DMD cardiomyopathy. As iMAOB are already in clinical use, such approach could be easily translated to patients.

Improving screening, brief intervention and referral to treatment for unhealthy alcohol use in diverse, low-resourced primary care clinics.

Implementation of screening brief intervention and referral to treatment (SBIRT) and medication-assisted treatment for alcohol use disorder (MAUD) remains low in primary care. ANTECEDENT (Partnerships to Enhance Alcohol Screening, Treatment, and Intervention) was a practice-facilitator led implementation study to increase SBIRT and MAUD use in diverse primary care clinics. From November 2019 - April 2023, we conducted a convergent parallel mixed methods evaluation. Participants were small and medium-sized primary care clinics in the Northwestern U.S. Clinics received foundational support (i.e., baseline/exit assessment, access to SBIRT Oregon website) and the option for supplemental implementation support (e.g., practice facilitation, expert consultation) over the 15-month intervention to improve SBIRT and MAUD. Qualitative and quantitative data regarding clinic characteristics, implementation strategies, and SBIRT/MAUD outcomes were collected through practice facilitator interviews, periodic reflections and clinic contact logs, interviews, pre-post surveys, and electronic health record (EHR) queries. Quantitative analyses included descriptive statistics, logistic regression, and the Wilcoxon sign-ranked test. Qualitative analysis took an immersion crystallization approach. Data were reviewed in a matrix to evaluate intervention adoption, implementation, and effectiveness. We recruited 75 unique clinics; 66 participated and 48 (73%) completed the study. Eight participating clinics chose to receive foundational support only (12%) while 58 chose to engage in supplemental support (88%) activities. Clinics that received supplemental support and completed the intervention (n = 42) engaged in practice facilitation (Mean: 293min, range: 75-550min); data review (38%), HIT support (31%), expert consultation (19%), and peer-to-peer learning (5%). Pre- and post-intervention assessments showed significant improvement in self-reported SBIRT process outcomes. Performance data improved among the subset of completing clinics able to produce data (n = 17). Clinics described positive experiences with ANTECEDENT support and highlighted remaining barriers to SBIRT and MAUD implementation. Participating clinics engaged in a diverse range of supportive activities. A flexible approach using practice facilitation and implementation support could be helpful for low-resourced primary care clinics in improving SBIRT and MAUD for unhealthy alcohol use.

Training, practice, and career considerations in forensic psychology: results from a field survey of clinical and non-clinical professionals in the United States

The current field survey describes the identities, training, practices, and careers of 351 U.S. forensic psychologists. Findings are presented for clinical forensic psychologists (n = 323) with additional consideration for those working in institutions (n = 119), private practice (n = 107), or both (n = 90), and separately for non-clinical forensic psychologists (n = 35). The sample was predominantly middle-aged, White, and female. Participants reported various training paths to the field, and professional settings and activities in the field. Student loan debt was common and significant in clinical Forensic psychologists. Income was generally high, with trends in higher incomes for private practice, board certification, urban areas, and certain geographic regions. Gendered income disparities were common, particularly among those later in their careers and in private practice, with relative parity only observed among early-career clinical forensic psychologists in institutions. Career satisfaction was generally high, with some important barriers noted. Overall, the limited representation of those with historically marginalized cultural identities restricted further consideration and understanding of these important factors in the field. Additional data and discussion are provided for these and other areas of demographics and lived experiences, training and related financial considerations, professional practices (including settings, activities, and clinical test use), and career considerations (including income, benefits, retirement planning, and satisfaction). Together, these data and related discussions offer important insights for prospective and current trainees entering the field, professionals seeking to navigate and advance their careers, and field leaders aiming to contribute to the ongoing development of forensic psychology.