Early Assessment Research Articles

Play-Based Assessment: Psychometric Properties of an Early Childhood Learning and Development Assessment Battery

This study aims to explore the reliability, construct validity, and content validity of the Child Learning and Developmental Playful Assessment Battery (Batería de Evaluación Lúdica del Aprendizaje y Desarrollo Infantil; BELADI), a quantitative instrument based on the authentic assessment and playful learning principles, the purpose of which is to assess infant learning and development through motor and competitive games as well as storytelling. The sample was composed of 113 children from Albacete (Spain) between 58 and 72 months of chronological age (M = 64.72; SD = 3.671). To explore the content validity, an expert judgement was carried out and the Content Validity Coefficient (CVC) was calculated. The reliability was analysed using the Cronbach’s alpha and McDonald’s Ω, and an exploratory factor analysis (EFA) was conducted. The results revealed high reliability indexes in each of the developmental domains, and the EFA included 11 items distributed in two factors for the psychomotor domain, 27 items grouped in three factors for the cognitive domain, and 20 items divided into four factors for the socioemotional domain. In conclusion, the study verifies the validity and reliability of the BELADI for the assessment of the infant learning and development through play, which may be used in research, education, and psychopedagogy.

Prognostic Value of Serum D-dimer in Predicting Outcomes in COVID-19 Positive Pregnant Women

Background: Combined effects of pregnancy induced hypercoagulability and SARS-CoV-2 infection place pregnant women with COVID-19 disease at high risk of severe outcome. COVID-19 severity has also been associated with serum D-dimer, a biomarker reflecting coagulation and fibrin degradation, in general populations. Despite its prognostic value in pregnant women, the prognostic value of this finding particularly in maternal outcomes remains less understood. The aim of this study was to determine whether elevated serum D-dimer levels in pregnant COVID-19 positive women are of prognostic significance for severe maternal outcomes. Methods: This retrospective observational study included 62 third trimester COVID 19 positive pregnant women admitted to the Department of Obstetrics and Gynecology, BSMMU, Dhaka from March 2019 to February 2020. Serum D-dimer were measured at admission and day 7, 14. D-dimer levels were related to clinical outcomes and statistically evaluated using chi square tests and logistic regression at p < 0.05. Results: Significantly associated with higher risk of severe outcomes, all of which included ICU admission, respiratory complications and adverse pregnancy events is elevated D-dimer levels (≥1.5 mg/L). In logistic regression analysis, patients with D-dimer levels of ≥1.5 mg/L had 3.5-fold greater odds of severe outcomes (OR 3.486; 95% CI, 1.184 to 10.263; p = 0.023). D-dimer had a sensitivity of 64.29%, 67.55% specificity in predicting severe outcomes. Conclusion: Serum D-dimer is valuable prognostic marker of disease severity in pregnant COVID-19 positive women and may be used for early risk assessment and clinical decision making. Routine measurement may help identify early high risk cases in order to improve maternal outcomes.

Abstract 4120657: A Personal Risk Assessment Device in Patients with Chest Pain

Introduction: Early prehospital chest pain assessment improves acute coronary syndrome (ACS) outcomes and can reduce unnecessary Emergency Room (ER) visits but requires medical personnel and electrocardiographic (ECG) equipment. Objective: To evaluate the feasibility of a personal credit-card sized chest pain self-assessment device (HeartBeam, Santa Clara, CA, USA) in diagnosing ACS. Methods: ACS risk was estimated by serial likelihood ratio analysis of 3 components: pre-existing coronary heart disease (CHD) risk (pre-calculated based on pooled ASCVD equation), chest pain characteristics (interactive proprietary questionnaire), and integrated near-orthogonal 3-lead self-recorded vectorcardiogram (VCG) with optional comparison to baseline using portable handheld HeartBeam recorder. Final ACS risk was graded High/Intermediate/Low by the cloud-based proprietary algorithm. High risk was considered positive for ACS. Results: 184 ER patients with chest pain (Age 57 +/- 7years, 90 Male, 43 (23%) ACS) comprised learning (n=96) and test (n=88) sets. ACS sensitivity was 28/28 (100%) in learning and 15/16 (94%) in test set with specificity of 43% and 42% respectively. In the subset of patients with pain-free portable VCG recorded 9 months later used as a “reverse baseline” (n=110) sensitivity was 17/17 (100%) and 11/12 (92%), specificity 54% and 58% in learning and test set, respectively (p>0.1 with no baseline). Single patient missed by the analysis had known coronary disease with usual anginal episode resulting in minor troponin leak. In “reverse baseline” analysis 41/110 (37%) patients were classified as Low risk compared to 18/184 (10%) without baseline (p<0.001), all negative for ACS. Based on the analysis of CHD risk factors, chest pain characteristics, and 12-lead ECG, a consensus of 3-member ER chest pain unit physicians panel had sensitivity/specificity of 94/54% for the whole and 93/48% for the “reverse baseline” groups (p>0.1 with HeartBeam device). Conclusion: HeartBeam chest pain self-assessment device provides accurate ACS detection comparable to expert ER physicians using 12 lead ECG. The presence of baseline recording reduces the number of false positive results. If confirmed in larger studies, it can be used to facilitate outpatient chest pain assessment and triage by remote physicians and patients themselves.

Complex Exploration of Bilateral Patellofemoral Instability and Integrated Management in the Context of Grade 2 Knee Gonarthrosis

This article delves into the intricate realm of bilateral patellofemoral instability and its correlation with Grade 2 Knee Gonarthrosis. Bilateral patellofemoral instability, characterized by dysfunctions in the rotational movements of the patella in relation to the femur, is often intertwined with the degenerative processes of knee Gonarthrosis. Examining this association, the article scrutinizes the impact of bilateral patellofemoral instability on the progression of knee gonarthrosis and vice versa. It emphasizes the significance of early diagnosis and accurate assessment of patellofemoral instability, considering its substantial implications on knee joint function and longevity. Based on these investigations, the article advocates for an integrated approach in managing patients with bilateral patellofemoral instability and Grade 2 Knee Gonarthrosis. In conclusion, the article underscores the need for a multidisciplinary approach to efficiently address patients with bilateral patellofemoral instability associated with Grade 2 Knee Gonarthrosis. By comprehending the complexities of these conditions, healthcare professionals can offer tailored solutions and enhance the quality of life for patients.

NIMG-16. ASSESSMENT OF RESPONSE TO LOMUSTINE-TEMOZOLOMIDE CHEMOTHERAPY IN ADDITION TO RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA USING FET PET

Abstract BACKGROUND We examined the value of O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET for early response assessment in patients with newly diagnosed glioblastoma and methylated O6-methylguanine-DNA methyltransferase promoter treated with lomustine-temozolomide chemotherapy in addition to radiotherapy. METHODS Thirty-one patients (29-74 years) were treated according to the CeTeG/NOA-09 phase-3 trial. FET PET and anatomical MRI were performed at baseline and follow-up after the third cycle. We obtained mean and maximum tumor-to-brain ratios (TBR) and metabolic tumor volumes (MTV). Thresholds derived from FET PET were defined using receiver operating characteristic analyses to predict progression-free survival (PFS) of ≥12 months. The predictive value of FET PET parameters was subsequently evaluated using univariate and multivariate survival estimates. MRI response assessment was based on the RANO 1.0 criteria. FET PET data were also used to estimate response according to the PET RANO 1.0 criteria. RESULTS Patients received a median number of 6 cycles of lomustine-temozolomide chemotherapy (3-6 cycles). After treatment initiation, the median follow-up was 17.2 months (7.2-59.4 months). As of April 2024, we confirmed tumor progression according to the RANO 1.0 criteria in 24 patients (77%). After three cycles of lomustine-temozolomide chemotherapy, a reduced mean TBR value by ≥10% predicted a significantly longer PFS (31.0 vs. 10.4 months; P=0.039). In contrast, changes in maximum TBR values, MTV, the RANO 1.0 criteria, and the PET RANO 1.0 criteria were not predictive for response (P>0.05). Multivariate survival analysis revealed that changes in mean TBR values predicted a significantly prolonged PFS independent of age, the extent of resection, and the Karnofsky Performance Status (P=0.036; HR, 3.892; 95% CI, 1.242-17.230). CONCLUSION Our results suggest that FET PET is clinically valuable for identifying responders to lomustine-temozolomide chemotherapy in addition to radiotherapy early after treatment initiation. The evaluation of FET PET’s value in predicting a significantly longer overall survival is ongoing.

Innovative Digital Learning

This poster highlights the effective use of learning technologies like animation, generative AI tools, and immersive reality to create digital learning and assessment artifacts for university nursing students. The purpose is to deliver a high-quality digital learning experience aligned with the university's pedagogy and education plan. It also showcases accessible, inclusive digital artifacts and early evaluations of their impact on learning. Animation technology is at the forefront of creating engaging educational content. By using animation, complex concepts can be shown in a visually appealing and easily digestible manner, making learning more engaging for students (Liu & Elms, 2019). It also allows for dynamic storytelling and the illustration of abstract ideas, which can be particularly beneficial in concepts that are challenging to visualize (Rasmusson & Bourne, 2017). Generative AI plays a pivotal role in developing scripts for these educational animations. Leveraging AI, we generate content tailored to learners' needs and optimized for clarity and engagement. Though AI-generated, our academic team thoroughly edits and revises the scripts to be clinically representative of the topic covered. This AI-driven script development ensures efficient collaboration with academics, resulting in accurate, relevant, and pedagogically sound material. (ProQuest LLC, 2024). Using cutting-edge animation and generative AI technologies can create impactful nursing education materials that boost student engagement. (White, Huang, & Campanale, 2023) and facilitate learning outcomes (Huang et al., 2020). These activities are anchored in the university’s signature pedagogy—active, applied, and authentic—immersing students in educational content and inspiring them to apply their knowledge and skills in real-world scenarios presented through animated learning activities. In addition, immersive reality technologies, including Virtual Reality (VR) and Augmented Reality (AR), further enhance the educational experience. By incorporating AR and VR as additional resources to complement the animations, we create immersive environments where students can interact with the material in a hands-on manner. This not only can make learning more engaging but can also help students better understand and retain complex concepts through experiential learning (Tene et al., 2024). A digital learning developer collaborated with the academic team to create an augmented reality-based artifact for nursing students. Integrated into Canvas our institution’s learning management system this artifact presented difficult topics in three dimensions with the aim of effectively explaining concepts and enhancing student engagement. While animation and immersive technologies can boost engagement, they can also present inclusivity and accessibility challenges for some students. To facilitateinclusivity and accessibility, we followed digital accessibility guidelines and universal design principles (Ismailov & Chiu, 2022). We evaluated tools like animation, AR/VR, and interactive modules for accessibility, offering alternatives when needed. This approach accommodated diverse learning preferences, making education accessible and inclusive for all students. The environmental impact of adopting these technologies is a significant consideration. Digital tools can reduce the need for physical materials and decrease travel-related emissions, making education more sustainable. The early assessment of the digital learning materials, incorporating animation, AI, and immersive learning technologies, reveals promising results in enhancing student engagement. These materials cater to various learning preferences reflecting insights from the academic team.

THE IMPACT OF EXOGENOUS AND ENDOGENOUS FACTORS ON VASCULAR WALL ELASTICITY AND POTENTIAL CLINICAL EFFECTS (Review Article)

Vascular aging is associated with profound changes in the structural properties of the arterial wall. Arterial hypertension, diabetes mellitus, and chronic kidney disease are the primary determinants of the loss of elasticity and reduced compliance of the vascular wall. Arterial stiffness is a key parameter for assessing the elasticity of the arterial wall and can be easily evaluated using non-invasive methods such as pulse wave velocity. Early assessment of arterial stiffness is critical, as its changes may precede the clinical manifestations of cardiovascular disease. With age, arterial walls become stiffer, leading to an increase in systolic blood pressure and an increased risk of cardiovascular events such as stroke, myocardial infarction, or heart failure. The gradual decrease in vascular elasticity is accompanied by remodeling of their structure, an increase in collagen fibers, and a decrease in elastin, which exacerbates the problem. In addition, the mechanical stress on the vascular wall, which increases with age, worsens its condition, provoking the formation of atherosclerotic plaques. Arterial stiffness, as an important biomarker of vascular aging, is also an indicator of increased cardiovascular risk, independent of other factors such as blood pressure or the presence of comorbidities. Therefore, timely diagnosis of arterial stiffness can help prevent serious complications and adjust treatment for patients at risk. Important are also preventive measures, including a healthy lifestyle, physical activity, and control of the underlying diseases that contribute to the acceleration of vascular aging processes. Moreover, the influence of endogenous and exogenous factors, such as diet, the presence of chronic diseases, and bad habits (in particular, smoking), contribute to the acceleration of these processes. Innovative diagnostic methods, such as magnetic resonance imaging (MRI) or ultrasound, allow detecting these changes at early stages and, accordingly, adapting treatment.

TMOD-02. PATIENT-DERIVED GLIOBLASTOMA ORGANOIDS AS REAL-TIME AVATARS FOR ASSESSING RESPONSES TO CLINICAL CAR-T CELL THERAPY

Abstract Patient-derived tumor organoids have been increasingly leveraged for disease modeling and preclinical studies, but rarely in real-time to aid with the interpretation of patient treatment responses in the clinical setting. Whether tumor organoids can be applied to mirror clinical activity in patients and even to predict responses for personalized medicine remains uncertain. We recently demonstrated promising early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor T cells (EGFR-IL13Rα2 CAR-T cells) in patients with recurrent glioblastoma (clinical trial identifier: NCT05168423). Determination of meaningful clinical efficacy, in particular for CAR-T cell therapy, may take months to manifest. Given this challenge, real-time analysis of patient-derived glioblastoma organoids (GBOs) could help to provide early assessment of clinical efficacy and guide patient management. We analyzed six sets of GBOs generated on the same timeline as the production of patients’ CAR-T cell products. GBOs demonstrated the presence and retention of both targeted tumor-associated antigens EGFR and IL13Rα2 by immunohistochemistry. These GBOs were then treated with the same autologous CAR-T cell products received by patients in our phase 1 study in parallel with patient treatment. CAR-T cell treatment led to target antigen reduction assessed by immunohistochemistry and flow cytometry. Furthermore, we confirmed cytolysis of tumor cells in GBOs by cleaved caspase-3 immunostaining and by co-culture in the Axion Maestro Cellular Impedance platform. Importantly, the degree of cytolysis ex vivo significantly correlated with CAR-T cell engraftment detected in patients’ cerebrospinal fluid (CSF) for all six patients. Furthermore, cytotoxic activity of CAR-T cells as measured by TNFα, IL-2, and IFNγ release kinetics in GBOs mirrored cytokine levels in patient CSF samples over time. Our findings highlight a unique trial design and suggest GBOs as a valuable platform for real-time assessment of CAR-T cell bioactivity and for insights into immunotherapy efficacy.

Nutritional disorders and nutrition-related conditions: an underestimated clinical problem in systemic sclerosis

Nutritional disorders are significant but often underestimated complications in patients with systemic sclerosis (SSc). The most prevalent nutritional disorders in SSc are malnutrition, affecting up to 62.5% of patients, and sarcopenia, with a frequency of up to 42%. Thus, clinical vigilance is recommended for the detection of eating disorders in SSc patients, particularly those with gastrointestinal involvement, cardiopulmonary complications, an advanced disease stage, and high disease activity. Nutritional treatment should be carefully tailored to the patients’ clinical condition to ensure that it effectively addresses their specific needs. Studies focusing on enteral nutrition in SSc patients demonstrate its effectiveness in stabilizing or improving nutritional status in malnourished patients. In severe cases, parenteral nutrition offers viable options to support patient health. The findings highlight the importance of early nutritional assessment and intervention in improving patient outcomes and suggest that individualized nutritional therapy can be a critical component of comprehensive care for SSc patients.

Mental Health Identification System

In an era where technology's reach extends to the intricacies of human well- being, "Mental Health Identification" emerges as a thought-provoking narrative that explores the convergence of innovation, ethics, and mental health. Relationships strain under the weight of newfound possibilities, underscoring. Developing an AI-Enabled Mental Health Identification for Early Intervention This project introduces an innovative AI-enabled mental health identification designed to revolutionize the early identification of mental health conditions. The project’s goal is to create a valuable tool that contributes to improved mental health awareness and support. The abstract provides a concise overview of the project. It highlights the development of an artificial intelligence-based mental health identification that utilizes cutting- edge machine learning algorithms to analyze face patterns, facial expressions, and textual inputs. The project’s focus is on creating an automated and non-intrusive tool for early detection and assessment of mental health conditions, aiming to contribute to improved mental health awareness and support. Mental health disorders have become one of the leading causes of disability worldwide, affecting millions of individuals. The early identification of mental health conditions is crucial for effective treatment and prevention. This paper presents a Mental Health Identification System that utilizes machine learning algorithms to predict and identify common mental health disorders based on a questionnaire dataset. The model is designed to focus on anxiety, depression, and stress disorders, using classification techniques to analyze user inputs

Temporal Bone Gunshot Wounds: A Multi-institutional Retrospective Study.

To investigate management practices and outcomes in a retrospective cohort of patients who have sustained temporal bone gunshot wounds (TBGSW). Retrospective chart review. Five participating hospitals. Twenty-two patients met inclusion criteria: experienced a TBGSW, survived ≥30 days following the injury, and were evaluated and managed by a neurotologist between 2019 and 2023. No specific interventions were performed for the purposes of this study. Characteristics, evaluation, management, and outcomes of TBGSW survivors. Patients were found to have a mean age of 33 ± 18 years and were predominantly male (18/22, 81.8%). Majority of patients (17/22, 77.3%) had mastoid injury. Most patients (14/22, 63.6%) had some evidence for vascular injury, most frequently the internal carotid artery (9/22, 40.9%). Almost three-quarters (17/22, 77.3%) of patients had clinical exam findings of facial nerve injury, which was the most common indication for surgery. Otologic surgery was performed in 72.7% (16/22), with delayed adverse events most commonly including cholesteatoma and external auditory canal stenosis. Though evidence for hearing impairment was clinically present in at least 15 of 22 patients (68.2%), hearing rehabilitation was pursued in only two patients. With increasing numbers of TBGSW survivors, there is a growing need for practicing neurotologists to be familiar with the wide spectrum of injury patterns and possible complications to inform clinical management in these patients. Early neurotologic assessment and follow-up beyond the acute period is crucial to minimize morbidity in this high-risk cohort.

Cell Painting and Chemical Structure Read-Across Can Complement Each Other for Rat Acute Oral Toxicity Prediction in Chemical Early Derisking.

Early derisking decisions in the development of new chemical compounds enable the identification of novel chemical candidates with improved safety profiles. In vivo studies are traditionally conducted in the early assessment of acute oral toxicity of crop protection products to avoid compounds, which are considered "very acutely toxic", with an in vivo lethal dose of 50% (LD50) ≤ 60 mg/kg body weight. Those studies are lengthy and costly and raise ethical concerns, catalyzing the use of nonanimal alternatives. The objective of our analysis was to assess the predictive efficacy of read-across approaches for acute oral toxicity in rats, comparing the use of chemical structure information, in vitro biological data derived from the Cell Painting profiling assay on U2OS cells, or the combination of both. Our findings indicate that the classification of compounds as very acute oral toxic (LD50 ≤ 60 mg/kg) or not is possible using a read-across approach, with chemical structure information, morphological profiles, or a combination of both. When classifying compounds structurally similar to those in the training set, the chemical structure was more predictive (balanced accuracy of 0.82). Conversely, when the compounds to be classified were structurally different from those in the training set, the morphological profiles were more predictive (balanced accuracy of 0.72). Combining the two models allowed for the classification of compounds structurally similar to those in the training set to slightly improve the predictions (balanced accuracy of 0.85).

SPECT/CT in Early Response Assessment of Patients with Metastatic Castration-Resistant Prostate Cancer Receiving 177Lu-PSMA-617.

177Lu-PSMA-617 (LuPSMA) is a newly established treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), but survival outcomes vary widely, and predictors of treatment responses are needed. This study investigated the role of total tumor volumes (TTVs) and new lesions (NLs) determined by LuPSMA SPECT/CT in early cycles to predict subsequent outcomes in a real-world practice setting. Methods: Between June and December 2022, consecutive patients with mCRPC who received at least 2 administrations of LuPSMA with SPECT/CT 24 h after treatment were retrospectively reviewed. We evaluated associations between TTVs and the appearance of NLs at cycles 2 and 3 with subsequent prostate-specific antigen (PSA) progression-free survival and overall survival (OS) using multivariate Cox regression. All analyses were adjusted for changes in PSA level relative to baseline. Results: Sixty-six mCRPC patients (median age, 74 y) received a median of 4 (interquartile range, 3-5) cycles of LuPSMA. Median follow-up starting at cycle 2 was 42 wk (interquartile range, 33-48 wk), with 24 of 66 patients deceased at the time of the analysis. Changes in TTV measured at the start of cycles 2 and 3 relative to baseline correlated significantly with corresponding changes in PSA level (r = 0.55 and 0.56), but absolute TTVs did not correlate significantly (r = 0.00 and 0.18). Patients with a higher absolute TTV at the start of cycle 2 had worse PSA progression-free survival and OS (hazard ratio [HR], 1.4 [95% CI, 1.1-1.8] and 2.1 [95% CI, 1.5-2.9]), with consistent results at the start of cycle 3 (HR, 2 [95% CI, 1.4-2.9] and 2 [95% CI, 1.2-3.2]). NLs were identified in 13 of 66 and 11 of 51 patients at the start of cycles 2 and 3. NLs at the start of cycle 2 were associated with worse OS (HR, 5.8 [95% CI, 1.9-17.5]), with consistent results at the start of cycle 3 (HR, 4.9 [95% CI, 1.3-18.6]). In multivariate analysis, a higher TTV and the appearance of NLs at the start of cycles 2 and 3 were independently associated with poorer OS. Conclusion: Higher TTVs and NLs on LuPSMA SPECT/CT at the start of cycles 2 and 3 were independently associated with higher risk of death. These measures provided prognostic information independent of changes in PSA. Development of prognostic and predictive models including TTV, NLs, and PSA changes is warranted.

Validity of the Chronic Pain Grade Scale in nonspecific chronic low back pain

Higher pain grades are associated with high psychological burden and increase the risk for the persistence of chronic low back pain (CLBP). Previous results on the criterion validity of the Chronic Pain Grade Scale (CPGS) have been extended to the context of inpatient multidisciplinary orthopedic rehabilitation (MOR) and have been supplemented with additional psychosocial and work-related measures. In this multicenter study, psychological, work- and pain-related outcomes were examined among 1010 individuals with nonspecific CLBP (ICD-10: M51/53/54) prior to the beginning of an inpatient MOR stratified by pain grade (I-IV). Additionally, frequency distributions of scores regarding pain-specific self-efficacy, depression, and subjective prognosis of gainful employment by pain grade in patients were investigated. The CPGS differed between all pain grades in the psychological, work- and pain-related outcomes in the expected direction. In post hoc pairwise comparisons, gradeIV was significantly different from the lower grades. Patients with higher pain grades showed unfavorable levels in psychosocial parameters and more frequently scores in the clinical range than expected. These results confirm the criterion validity of the CPGS. The psychosocial risk pattern observed in higher pain grades supports the importance of conducting early pain-related and psychological diagnostic assessments and implementing systematic allocation to needs-based interdisciplinary multimodal treatments.

Relationship between lactate levels and 28-day mortality in pediatric sepsis: results from the pediatric intensive care database

ObjectiveThis study aimed to investigate the relationship between serum lactate levels at admission to the intensive care unit (ICU) and the clinical outcomes of children with sepsis.MethodsWe used the Pediatric Intensive Care (PIC) database to identify 288 pediatric patients with sepsis. We analyzed the relationship between lactate levels and hospital and ICU mortality in sepsis by establishing a segmented multivariable Cox regression model. We also conducted subgroup analysis as well as analyzed the restricted cubic spline curves.ResultsAfter adjusting for all potential confounding factors, an increase of 1 mmol/L in lactate levels was found to be associated with an 17% rise in the 28-day hospital mortality risk among sepsis patients (HR: 1.17, 95% CI: 1.08–1.27, P = 0.0002). When considering lactate as a categorical variable, the mortality risk of patients with lactate levels ≥ 2.2 mmol/L was significantly increased (HR: 3.61, 95% CI: 1.24–10.54, P = 0.0189). The restricted cubic spline curve analysis revealed a nonlinear correlation between lactate and 28-day mortality, with an inflection point at 2.2 mmol/L. Similar findings were also observed in the assessment of secondary outcomes.ConclusionsOur study demonstrates a non-linear correlation between lactate levels and 28-day mortality in pediatric sepsis, with a critical threshold of 2.2mmol/l for lactate levels in septic patients. Early assessment of lactate levels is recommended for children with sepsis to facilitate prompt intervention and mitigate the risk of fatality.

Systemic immune inflammatory response index (SIIRI) in acute myocardial infarction.

Different treatment approaches exist for non-ST elevation acute coronary syndrome (ACS) patients. This study assessed the systemic immune inflammatory response index (SIIRI) for its prognostic value and incremental clinical utility in determining optimal timing for percutaneous coronary intervention (PCI) in non-ST elevation myocardial infarction (NSTEMI) patients, particularly when troponin levels are initially negative. This study included 1270 ACS patients: 437 STEMI, 422 NSTEMI, and 411 unstable angina. Patients were stratified by SIIRI levels measured at admission, and coronary artery disease severity was evaluated using the SYNTAX score. The primary endpoint was major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, stroke, and revascularization. Secondary endpoints encompassed individual MACE components and heart failure hospitalisations. The mean age was 54.93 years (83% male). SIIRI levels were significantly higher in STEMI patients (6.83 ± 6.43 × 105) compared to NSTEMI (4.5 ± 5.39 × 105) and unstable angina (3.48 ± 2.83 × 105) (P < 0.001). Area under the curve for SIIRI distinguished NSTEMI and unstable angina from STEMI (0.81 and 0.80), with optimal cut-off points of 4.80 × 105 and 4.25 × 105. In NSTEMI, 24.6% presented within 2 h of symptom onset, were troponin-negative, yet had elevated SIIRI. Post-PCI, SIIRI > 4.93 × 105 correlated with increased MACE at 1 year (17.2% vs 5%). NSTEMI and unstable angina patients with SIIRI values >4.80 × 105 and 4.25 × 105 respectively, may require urgent intervention (<2 h). SIIRI can be of significant utility in patients of NSTEMI who present earlier with negative troponins. SIIRI can also aid in identifying high-risk individuals post-PCI, providing a valuable tool for early and accurate assessment.

Ethical implications of artificial intelligence in skin cancer diagnostics: use-case analyses.

Skin cancer is the most common cancer worldwide. Early diagnosis is crucial for improving patient survival and morbidity. Artificial intelligence (AI)-assisted smartphone applications (apps) for skin cancer potentially offer accessible, early risk assessment of suspicious skin lesions. However, the integration of novel technologies into dermatology pathways raises ethical concerns. Although ethical principles for AI governance are well known, how these principles should be applied to real-life AI apps readily available for public use is less well understood. We conducted an ethical use-case analysis of commercially available skin cancer apps to better understand the ethical issues arising from their development and use in a real-world context. Established methods for ethical analysis of clinical AI applications were applied to two popular skin cancer apps in the UK: SkinVision and Scanoma. Systematic searches of published literature, regulatory documents, and websites were conducted to review the evidence regarding app development, effectiveness, and use. Screening for inclusion was undertaken by two researchers independently. Ethical concerns were identified with reference to previously described ethical concerns and principles for AI-assisted healthcare. By conceptualising ethical principles within the use-context of skin cancer apps, we identified specific ethical issues arising throughout the AI lifecycle of both apps. One company provided extensive detail regarding algorithm development and decision-making, this information was insufficiently reported for the other app. Other concerns identified related to number, quality, and consistency of studies assessing algorithm efficacy. Limited efforts to address potential skin tone biases and exclusion of individuals with darker skin tones as target users by one app risks perpetuating existing inequalities. Inadequate regulatory oversight was identified. Findings from our ethical use-case analysis of two patient-facing AI-assisted skin cancer apps suggest inadequate incorporation of bioethical norms such as justice, responsibility and transparency into the development and deployment of both apps. Improved regulation should increase accountability. Ensuring ethics by design through integration between technology developers, dermatologists, ethicists, and the public is urgently needed to prevent the potential benefits of AI-assisted skin cancer apps being overshadowed by potential ethical harms.

Analysis of Reflectance Confocal Microscopy and Dermoscopic Imaging Features in Diagnosis and Treatment Evaluation of Extramammary Paget’s Disease: A Single-Center Retrospective Study

Objective: Extramammary Paget’s disease (EMPD) is often misdiagnosed as chronic dermatitis or eczema of the scrotum because of its clinical manifestations, leading to delayed diagnosis and treatment. Reflectance confocal microscopy (RCM) and dermoscopy are widely used in clinical practice, enabling early diagnosis and treatment assessment of skin lesions, particularly skin tumors. This study aimed to summarize the RCM and dermoscopic features of EMPD and evaluate treatment outcomes. Methods: We conducted a retrospective analysis of 104 skin lesions from 34 patients diagnosed with EMPD, confirmed through histopathological examination. These patients were treated at our outpatient clinic between January 2022 and December 2023. The analysis focused on typical changes, such as blood vessel patterns and background color under dermoscopy, as well as cellular morphology under RCM. Count data were presented as constituent ratios. Results: Among the 34 patients, 28 were male and 6 were female, and 104 skin lesions were identified. The lesions were classified into three types: 36 red patches, 41 dark red erosive patches, and 27 brown pigmented patches. Dermoscopic examination of EMPD revealed characteristic features, including milky white globules (90.4%, 94/104), irregular shiny white streaks (91.3%, 95/104), dotted blood vessels (91.3%, 95/104), and glomerular-like vessels (88.5%, 92/104). RCM demonstrated epidermal structural disorganization (100%, 104/100), vacuolated cells in the epidermis (94.2%, 98/104), and Paget cells, either scattered or clustered (88.5%, 92/104). The red macular lesions predominantly contained isolated vacuolated cells in the epidermis, the dark red erosive lesions exhibited Paget cell nests in the basal layer, and the brown pigmented lesions contained numerous dendritic cells. These findings are crucial for clinical assessment, ensuring complete tumor removal, and guiding postoperative follow-up. Conclusion: This study identified characteristic dermoscopic and RCM features in patients with EMPD, providing a foundation for non-invasive auxiliary diagnosis. These features facilitate earlier diagnosis and treatment. Additionally, RCM characteristics of different lesion morphologies can help physicians more accurately assess surgical margins, leading to more precise surgical treatment options.

Profiling Plasma Extracellular Vesicle Metabotypes and miRNAs: An Unobserved Clue for Predicting Relapse in Patients with Early-Stage NSCLC

Background and Objective: Lung cancer, the second most prevalent cancer globally, poses significant challenges in early detection and prognostic assessment. Despite advancements in targeted therapies and immunotherapy, the timely identification of relapse remains elusive. Blood-based liquid biopsy biomarkers, including circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), circulating-free RNAs (cfRNAs), and extracellular vesicles (EVs)/exosomes, offer promise for non-invasive monitoring. Methods: We employ a comprehensive approach integrating miRNA/lncRNA/metabolomic datasets, following a mixed-methods content analysis, to identify candidate biomarkers in NSCLC. NSCLC-associated miRNA/gene/lncRNA associations were linked to in silico-derived molecular pathways. Results: For data validation, mass spectrometry-based untargeted metabolomics of plasma EVs highlighted miRNA/lncRNA/metabotypes, linking “glycerophospholipid metabolism” to lncRNA H19 and “alanine, aspartate and glutamate metabolism” to miR-29a-3p. Prognostic significance was established for miR-29a-3p, showing lower expression in NSCLC patients with disease progression compared to stable disease (p = 0.004). Kaplan–Meier survival analysis indicated that patients with miR-29a-3p under-expression had significantly shorter overall survival (OS) (p = 0.038). Despite the expression of lncRNA H19 in plasma EVs being undetected, its expression in plasma cfRNAs correlated significantly with disease progression (p = 0.035). Conclusions: Herein, we showcase the potential of plasma EV-derived miR-29a-3p as a prognostic biomarker and underscore the intricate interplay of miRNAs, lncRNAs, and metabolites in NSCLC biology. Our findings offer new insights and avenues for further exploration, contributing to the ongoing quest for effective biomarkers in early-stage NSCLC.

HIF-1Α IN SALIVA: A PROMISING BIOMARKER FOR EARLY DIAGNOSIS OF ORAL SUBMUCOUS FIBROSIS AND ITS MALIGNANT POTENTIAL

Oral submucous fibrosis (OSF) is a chronic condition with a high risk of transforming into oral squamous cell carcinoma (OSCC). Identifying reliable biomarkers for early diagnosis and monitoring of OSF is crucial for malignancy prevention. Objective: This study evaluates the expression of Hypoxia Inducible Factor-1α (HIF-1α) in saliva as a potential biomarker for OSF. Methods: Study was a cross-sectional study conducted in Karachi. The study was completed in 6 months from July 2023 to December 2023 and Sixty-five OSF patients participated in the study, providing saliva samples analyzed for HIF-1α expression using immunohistochemically (IHC). Clinic pathological features, including age, gender, body mass index (BMI), and etiological factors (tobacco, smoking, areca nut), were documented. Relationships between clinical symptoms (burning sensation, pain, ulceration, and dry mouth), fibrosis severity, and HIF-1α staining intensity in blood vessels and fibroblasts were assessed. Results: The study population included 68.3% males and 31.7% females, with a mean age of 32.56±4.12 years. Tobacco use (47.7%) was the most common etiology. HIF-1α expression was significantly elevated in fibroblasts compared to blood vessels, with mild staining in 54.2% of blood vessels and 49.8% of fibroblasts. Increased HIF-1α expression correlated with more severe OSF symptoms, indicating a higher risk of malignant transformation. Conclusion: HIF-1α is a promising biomarker for early diagnosis and assessment of malignant potential in OSF. Early detection and monitoring could improve clinical management and reduce OSCC risk, warranting further research for validation and therapeutic targeting.