Clinical Perspective Research Articles

Human In Vitro Models of Neuroenergetics and Neurometabolic Disturbances: Current Advances and Clinical Perspectives.

Neurological conditions conquer the world; they are the leading cause of disability and the second leading cause of death worldwide, and they appear all around the world in every age group, gender, nationality, and socioeconomic class. Despite the growing evidence of an immense impact of perturbations in neuroenergetics on overall brain function, only little is known about the underlying mechanisms. Especially human insights are sparse, owing to a shortage of physiologically relevant model systems. With this perspective, we aim to explore the key steps and considerations involved in developing an advanced human in vitro model for studying neuroenergetics. We discuss biological and technological strategies to meet the requirements of a predictive model, aiming at providing a guide and inspiration for future in vitro models of neuroenergetics.

Low-dose aspirin for the prevention of atherosclerotic cardiovascular disease.

During the past 30 years, several developments have occurred in the antiplatelet field, including the role of aspirin in primary prevention of atherosclerotic cardiovascular disease. There have been several attempts to develop antiplatelet drugs more effective and safer than aspirin and a shift in emphasis from efficacy to safety, advocating aspirin-free antiplatelet regimens after percutaneous coronary intervention. Evidence supporting a chemopreventive effect of low-dose aspirin against colorectal (and other digestive tract) cancer has also strengthened. The aim of this article is to revisit the role of aspirin in the prevention of atherothrombosis across the cardiovascular risk continuum, in view of developments in the antiplatelet field. The review will offer a clinical perspective on aspirin's mechanism of action, pharmacokinetics, and pharmacodynamics. This will be followed by a detailed discussion of its clinical efficacy and safety.

Singular entry point technique for forehead and temple filler augmentation: Anatomical and clinical perspectives.

The depressed volume of the forehead and temple is resolved by filler injection. However, the current method has the potential to cause pain and side effects in patients, depending on the skill of the clinician. Therefore, this study proposes a new method for safer and simpler injection using only one injection entry point. Using the novel injection method, the filler was injected into the forehead and temple regions in three unembalmed cadavers and two healthy Korean volunteers. The cannula and filler locations were identified using dissection, ultrasonography, and three-dimensional (3D) scanning. Ultrasonographic images and dissection results showed that the filler injected into the cadavers was in the target layer. The cannula and filler were located on the layer as the supraperiosteal layer on the forehead and the supra deep temporal fascia layer in the temple. Finally, 3D scanning images showed that the filler was injected precisely and effectively into the forehead and temples of the volunteer who underwent the procedure. This method can reduce pain and minimize externally visible wounds caused by injections. The injected filler was naturally connected from the forehead to the temple and maintained for around 3 months. Additionally, it is possible to inject fillers into the forehead and temple at a constant and safe depth without requiring specific skills. It is expected that this method will become a universal method because it minimizes the burden on both patients and clinicians.

Use of Titanium Mesh During Frontal Sinus Setback in Facial Feminization Surgery: Clinical Outcomes and Perspectives.

Brow position, hairline shape, and forehead projection may confer cis-feminine identity, and facial feminization surgery (FFS) can improve gender dysphoria among transfeminine patients. Depending on the Ousterhout classification, burring, osteotomy, anterior frontal sinus setback, and augmentation, with subsequent fixation via metal or bioabsorbable plates, can address forehead projection. However, titanium mesh, often used in frontal sinus fracture repair, has not been described for forehead contouring in FFS. The purpose of this study was to study clinical outcomes associated with the use of titanium mesh for the stabilization of bone following anterior frontal sinus setback. A retrospective cohort study of trans-female and nonbinary patients undergoing primary FFS by our senior author between January 2021 and February 2023 was performed. Variables collected include demographics, Ousterhout classification, operative details, complications, and follow-up duration. Patients with prior FFS or facial trauma were excluded. Data were analyzed using SPSS, (IBM, Armonk, NY). Forty-three transfeminine patients were included for analysis. The cohort had an average age of 33.0±8.7 years and a median follow-up time of 3.0 months (IQR = 1.0-7.0). Among our cohort, 26 patients (60.5%) received titanium mesh and 17 patients (39.5%) underwent burring only for forehead contouring. There were no reported complications (ie, infection, hardware extrusion, or mucocele formation) or a need for forehead revisions among the entire cohort regardless of the frontal sinus reconstruction material utilized. Clinical outcomes were favorable among patients receiving titanium mesh anterior table fixation during FFS. Titanium mesh can be considered as an additional technique for frontal bossing reduction and anterior table fixation in FFS.

Dual analysis of IL-8 in non-small cell lung cancer: A clinical perspective on protein and RNA evaluation via imaging mass cytometry.

e15068 Background: The cytokine Interleukin-8 (IL-8) plays a pivotal role in the tumorigenesis and progression of non-small cell lung cancer (NSCLC), influencing both the tumor microenvironment and immune escape mechanisms. Given its significance, accurately assessing IL-8 levels at the protein and RNA levels could provide valuable insights into its prognostic value and inform therapeutic targeting strategies. This study utilizes imaging mass cytometry (IMC) to conduct a comprehensive evaluation of IL-8 expression in NSCLC, integrating both protein presence and gene expression analysis within the spatial context of the tumor microenvironment. Methods: Our approach leverages the capabilities of IMC to simultaneously detect protein and RNA levels of IL-8 in NSCLC tissue samples. For protein analysis, antibodies tagged with heavy metal isotopes specifically target IL-8, allowing for precise quantification and spatial localization within the tumor. Concurrently, RNA detection is achieved through hybridization probes designed for IL-8 mRNA, enabling the direct observation of gene expression patterns. This method provides a unique opportunity to correlate IL-8's protein abundance with its mRNA expression, offering insights into the regulatory mechanisms at play and their impact on the tumor's behavior and patient outcomes. Results: Preliminary data demonstrate a marked heterogeneity in IL-8 distribution at both the protein and RNA levels, with distinct patterns emerging that relate to tumor aggressiveness and immune infiltration. High IL-8 expression, identified through our integrated IMC approach, correlates with poor prognosis and reduced response to standard therapies, underscoring its potential as a biomarker for NSCLC management. Furthermore, the spatial analysis afforded by IMC highlights the microenvironmental niches where IL-8-mediated interactions could drive tumor progression and immune evasion. Conclusions: By employing IMC for the dual analysis of IL-8 protein and RNA in NSCLC, our study provides a comprehensive view of this cytokine's role in lung cancer pathology. The ability to visualize and quantify IL-8 expression within the spatial context of the tumor microenvironment opens new avenues for understanding its biological impact and for developing targeted therapies. Our findings advocate for the inclusion of IL-8 in the biomarker panel for NSCLC, with potential implications for patient stratification and personalized treatment planning. Future research will focus on expanding these observations to a larger cohort and exploring the therapeutic modulation of IL-8 as a strategy for improving NSCLC outcomes.

Generalized Confidence Intervals for Ratios of Standard Deviations Based on Log-Normal Distribution when Times Follow Weibull Distributions.

Modern anesthetic drugs ensure the efficacy of general anesthesia. Goals include reducing variability in surgical, tracheal extubation, post-anesthesia care unit, or intraoperative response recovery times. Generalized confidence intervals based on the log-normal distribution compare variability between groups, specifically ratios of standard deviations. The alternative statistical approaches, performing robust variance comparison tests, give P-values, not point estimates nor confidence intervals for the ratios of the standard deviations. We performed Monte-Carlo simulations to learn what happens to confidence intervals for ratios of standard deviations of anesthesia-associated times when analyses are based on the log-normal, but the true distributions are Weibull. We used simulation conditions comparable to meta-analyses of most randomized trials in anesthesia, and coefficients ofvariation . The estimates of the ratios of standard deviations were positively biased, but slightly, the ratios being 0.11% to0.33% greater than nominal. In contrast, the 95% confidence intervals were very wide (i.e., > 95% of P ≥ 0.05). Although substantive inferentially, the differences inthe confidence limits were small from a clinical or managerial perspective, with amaximum absolute difference inratios of 0.016. Thus, P < 0.05 isreliable, but investigators should plan for TypeII errors atgreater than nominal rates.

Operative Management of Y-Shaped Metatarsal with Biphalangeal Sixth Toe.

In the literature, there is no consensus regarding the surgical management of postaxial polydactyly, and few cases of polymetatarsia with polydactyly have been reported. Treatment of the complete deformity will prevent further foot and gait disorders. To identify literature relevant to the operative management of Y-shaped metatarsal with biphalangeal sixth toe and related skin and wound care to improve surgical treatment protocols from a clinical experience perspective. The authors searched several electronic databases in December 2022 for articles related to postaxial polysyndactyly in the feet and polymetatarsia. Databases searched included PubMed, SciELO, ScienceDirect, Cochrane Database of Systematic Reviews, and Google Scholar gray literature. Two independent researchers conducted the searches and read the article titles and abstracts. Studies were included if they were narrative reviews, case studies, or observational studies; written in English or Spanish; and published between 2012 and 2022. Nonhuman studies were excluded. Studies that met the inclusion criteria were fully evaluated. Disagreements between reviewers were resolved by consensus, and when there was no consensus, a senior researcher was consulted. The following data were extracted from the included studies using a standardized form: author and year of publication, study type, number of participants, sex, polydactyly location, polymetatarsia, type of polydactyly, participants' history of hereditary associated diseases or malformations, treatment, removal criteria, and timing of surgery. Authors evaluated 11 studies of postaxial polydactyly that included a total of 153 participants (64 men, 89 women). They also document their clinical experience with a surgical technique used in cases of bilateral postaxial polydactyly of the foot with a Y-shaped metatarsal with biphalangeal sixth toe. Surgical correction with lateral removal of the sixth toe is a resolutive treatment to improve the functionality of the foot, its aesthetic appearance, and the patient's quality of life. Case-specific treatment should be applied and tailored to meet the individual needs. The biomechanics of gait and shoe problems in these patients improve with surgical treatment, without presenting secondary aesthetic problems in skin care.

Multidimensional assessment of social cognition using non-immersive virtual reality in dementia with Lewy bodies and Alzheimer’s disease: an exploratory study

ABSTRACT Introduction Few studies have focused on social cognition in dementia with Lewy bodies (DLB), even though some brain structures being well known as underlying social cognitive processes are directly impacted in this disease. Furthermore, social cognition processes have been mostly studied independently using evaluations with poor ecological validity. We aimed at studying the ability of a new naturalistic and multidimensional social cognition task to reveal impairments in DLB patients. We chose to compare the profile of these patients with that of Alzheimer’s disease (AD) patients, for which social cognition is better preserved. Method Fifteen patients (DLB: n = 7; AD: n = 8) and 28 healthy controls underwent the REALSoCog task. They encountered several social situations (e.g. control versus transgressions) in a non-immersive virtual city environment allowing the assessment of moral cognition, cognitive and affective theory of mind (ToM), emotional empathy and behavioral intentions. Results The main results showed (i) a lower ability to detect transgressions in DLB patients, particularly conventional ones, whereas moral cognition seemed better preserved in AD patients; (ii) a cognitive ToM impairment in both DLB and AD patients, while affective ToM is impaired only in DLB patients; (iii) a decreased emotional empathy specifically observed in DLB patients; (iv) more inappropriate behavioral intentions, mainly in DLB patients, but also in some AD patients. Conclusions This study suggests the feasibility and potential interest of the REALSoCog task in revealing social cognition deficits, particularly for DLB patients by showing different social patterns as compared to AD patients. These results offer interesting clinical perspectives to develop more naturalistic tasks in such populations and for clinical differential diagnosis. Limitations and future perspectives are discussed.

Highlights of the 2023 Bethesda System for Reporting Thyroid Cytopathology, 3rd Edition

The Bethesda System for Reporting Thyroid Cytopathology (TBSRCT) is crucial for cytopathologists to use a standardized, category-based reporting system for thyroid fine needle aspirations and is effective for clear communication with the referring physicians. The new Bethesda System for Reporting Thyroid Cytopathology, the third edition in 2023, provides several key updates. The most important update is the assignment of only single name for each of the six diagnostic categories: (I) nondiagnostic; (II) benign; (III) atypia of undetermined significance; (IV) follicular neoplasm; (V) suspicious for malignancy; and (VI) malignant. An implied risk of malignancy (ROM) for each of six categories has been updated based on extensively published data since the second edition of TBSRTC in 2017 and offers both an average ROM for each category and the expected range of cancer risk. Estimated final ROM after excluding “Noninvasive Follicular Thyroid Neoplasm with Papillary Like Nuclear Features (NIFTP)” for each of six categories has been updated based on the reported mean decreases in the ROM if excluding NIFTP. For atypia of undetermined significance (AUS) category, the subcategorization is simplified and more formalized into 2 subgroups, AUS-nuclear atypia or AUS-other, based on the implied ROM and molecular profiling. For the pediatric thyroid disease, pediatric ROMs and management algorithms are newly added for the same six reporting categories for this age group. New or revised disease nomenclatures including high-grade follicular-derived carcinoma has been updated according to the recently published 2022 World Health Organization Classification of Thyroid Neoplasms. Brand new two chapters are added including clinical perspectives and imaging studies (Chap. 13) and the use of molecular and other ancillary tests (Chap. 14). The atlas is updated with new images to illustrate more effectively for new disease entity and diagnostic criteria.

Understanding How Pre- and Probiotics Affect the Gut Microbiome and Metabolic Health.

The gut microbiome, a complex assembly of microorganisms, significantly impacts human health by influencing nutrient absorption, the immune system, and disease response. These microorganisms form a dynamic ecosystem that is critical to maintaining overall well-being. Prebiotics and probiotics are pivotal in regulating gut microbiotacomposition. Prebiotics nourish beneficial bacteria, and promote their growth, while probiotics help maintain balance within the microbiome. This intricate balance extends to several aspects of health, including maintaining the integrity of the gut barrier, regulating immune responses, and producing metabolites crucial for metabolic health. Dysbiosis, or an imbalance in the gut microbiota, has been linked to metabolic disorders such as type 2 diabetes, obesity, and cardiovascular disease. Impaired gut barrier function, endotoxemia, and low-grade inflammation are associated with toll-like receptors influencing pro-inflammatory pathways. Short-chain fatty acids derived from microbial fermentation modulate anti-inflammatory and immune system pathways. Prebiotics positively influence gut microbiota, while probiotics, especially Lactobacillus and Bifidobacterium strains, may improve metabolic outcomes, such as glycemic control in diabetes. It is important to consider strain-specific effects and study variability when interpreting these findings, highlighting the need for further research to optimize their therapeutic potential. The aim of this report is therefore to review the role of the gut microbiota in metabolic health and disease and the effects of prebiotics and probiotics on the gut microbiome and their therapeutic role, integrating a broad understanding of physiological mechanisms with a clinical perspective.

Postoperative tumor treatment strategies: From basic research to clinical therapy

AbstractDespite progression in advanced treatments for malignant tumors, surgery remains the primary treatment intervention, which removes a large portion of firm tumor tissues; however, the postoperative phase poses a possible risk for provincial tumor recurrence and metastasis. Consequently, the prevention of tumor recurrence and metastasis has attracted research attention. In this review, we summarized the postoperative treatment strategies for various tumors from both basic research and clinical perspectives. We delineated the underlying factors contributing to the recurrence of malignant tumors with a substantial prevalence rate, related molecular mechanisms of tumor recurrence post‐surgery, and related means of monitoring recurrence and metastasis after surgery. Furthermore, we described relevant therapeutic approaches for postoperative tumor recurrence, including chemotherapy, radiation therapy, immunotherapy, targeted therapy, and photodynamic therapy. This review focused on the emerging technologies used for postoperative tumor treatment in recent years in terms of functional classification, including the prevention of postoperative tumor recurrence, functional reconstruction, and monitoring of recurrence. Finally, we discussed the future development and deficiencies of postoperative tumor therapy. To understand postoperative treatment strategies for tumors from clinical treatment and basic research and further guide the research directions for postoperative tumors.

Uncertainty quantification in multi-class segmentation: Comparison between Bayesian and non-Bayesian approaches in a clinical perspective.

Automatic segmentation techniques based on Convolutional Neural Networks (CNNs) are widely adopted to automatically identify any structure of interest from a medical image, as they are not time consuming and not subject to high intra- and inter-operator variability. However, the adoption of these approaches in clinical practice is slowed down by some factors, such as the difficulty in providing an accurate quantification of their uncertainty. This work aims to evaluate the uncertainty quantification provided by two Bayesian and two non-Bayesian approaches for a multi-class segmentation problem, and to compare the risk propensity among these approaches, considering CT images of patients affected by renal cancer (RC). Four uncertainty quantification approaches were implemented in this work, based on a benchmark CNN currently employed in medical image segmentation: two Bayesian CNNs with different regularizations (Dropout and DropConnect), named BDR and BDC, an ensemble method (Ens) and a test-time augmentation (TTA) method. They were compared in terms of segmentation accuracy, using the Dice score, uncertainty quantification, using the ratio of correct-certain pixels (RCC) and incorrect-uncertain pixels (RIU), and with respect to inter-observer variability in manual segmentation. They were trained with the Kidney and Kidney Tumor Segmentation Challenge launched in 2021 (Kits21), for which multi-class segmentations of kidney, RC, and cyst on 300 CT volumes are available. Moreover, they were tested considering this and other two public renal CT datasets. Accuracy results achieved large differences across the structures of interest for all approaches, with an average Dice score of 0.92, 0.58, and 0.21 for kidney, tumor, and cyst, respectively. In terms of uncertainties, TTA provided the highest uncertainty, followed by Ens and BDC, whereas BDR provided the lowest, and minimized the number of incorrect certain pixels worse than the other approaches. Again, large differences were seen across the three structures in terms of RCC and RIU. These metrics were associated with different risk propensity, as BDR was the most risk-taking approach, able to provide higher accuracy in its prediction, but failing to assign uncertainty on incorrect segmentation in every case. The other three approaches were more conservative, providing large uncertainty regions, with the drawback of giving alert also on correct areas. Finally, the analysis of the inter-observer segmentation variability showed a significant variation among the four approaches on the external dataset, with BDR reporting the lowest agreement (Dice = 0.82), and TTA obtaining the highest score (Dice = 0.94). Our outcomes highlight the importance of quantifying the segmentation uncertainty and that decision-makers can choose the approach most in line with the risk propensity degree required by the application and theirpolicy.

Screening embryos for polygenic disease risk: a review of epidemiological, clinical, and ethical considerations.

The genetic composition of embryos generated by in vitro fertilization (IVF) can be examined with preimplantation genetic testing (PGT). Until recently, PGT was limited to detecting single-gene, high-risk pathogenic variants, large structural variants, and aneuploidy. Recent advances have made genome-wide genotyping of IVF embryos feasible and affordable, raising the possibility of screening embryos for their risk of polygenic diseases such as breast cancer, hypertension, diabetes, or schizophrenia. Despite a heated debate around this new technology, called polygenic embryo screening (PES; also PGT-P), it is already available to IVF patients in some countries. Several articles have studied epidemiological, clinical, and ethical perspectives on PES; however, a comprehensive, principled review of this emerging field is missing. This review has four main goals. First, given the interdisciplinary nature of PES studies, we aim to provide a self-contained educational background about PES to reproductive specialists interested in the subject. Second, we provide a comprehensive and critical review of arguments for and against the introduction of PES, crystallizing and prioritizing the key issues. We also cover the attitudes of IVF patients, clinicians, and the public towards PES. Third, we distinguish between possible future groups of PES patients, highlighting the benefits and harms pertaining to each group. Finally, our review, which is supported by ESHRE, is intended to aid healthcare professionals and policymakers in decision-making regarding whether to introduce PES in the clinic, and if so, how, and to whom. We searched for PubMed-indexed articles published between 1/1/2003 and 1/3/2024 using the terms 'polygenic embryo screening', 'polygenic preimplantation', and 'PGT-P'. We limited the review to primary research papers in English whose main focus was PES for medical conditions. We also included papers that did not appear in the search but were deemed relevant. The main theoretical benefit of PES is a reduction in lifetime polygenic disease risk for children born after screening. The magnitude of the risk reduction has been predicted based on statistical modelling, simulations, and sibling pair analyses. Results based on all methods suggest that under the best-case scenario, large relative risk reductions are possible for one or more diseases. However, as these models abstract several practical limitations, the realized benefits may be smaller, particularly due to a limited number of embryos and unclear future accuracy of the risk estimates. PES may negatively impact patients and their future children, as well as society. The main personal harms are an unindicated IVF treatment, a possible reduction in IVF success rates, and patient confusion, incomplete counselling, and choice overload. The main possible societal harms include discarded embryos, an increasing demand for 'designer babies', overemphasis of the genetic determinants of disease, unequal access, and lower utility in people of non-European ancestries. Benefits and harms will vary across the main potential patient groups, comprising patients already requiring IVF, fertile people with a history of a severe polygenic disease, and fertile healthy people. In the United States, the attitudes of IVF patients and the public towards PES seem positive, while healthcare professionals are cautious, sceptical about clinical utility, and concerned about patient counselling. The theoretical potential of PES to reduce risk across multiple polygenic diseases requires further research into its benefits and harms. Given the large number of practical limitations and possible harms, particularly unnecessary IVF treatments and discarded viable embryos, PES should be offered only within a research context before further clarity is achieved regarding its balance of benefits and harms. The gap in attitudes between healthcare professionals and the public needs to be narrowed by expanding public and patient education and providing resources for informative and unbiased genetic counselling.

BRAFV600E Metastatic Melanoma Journey: A Perspective from a Patient and his Oncologist.

This article is co-authored by a patient with BRAFV600E metastatic melanoma and his treating oncologist. The patient describes how he coped with his diagnosis and treatment. He details the pathway of his melanoma treatment, which has spanned over 10 years, including surgical interventions, medical treatment, and participation in clinical trials. He relates his experience of living with the disease-and the adverse effects of treatment-in the long term. The clinical perspective of his treating oncologist reviews the diagnostic process and explains how the therapeutic options were selected for and with the patient. The oncologist also addresses the integration of the patient into clinical trials involving programmed death-1 (PD-1) inhibitors and BRAF/MEK inhibitors. Challenges related to the adverse effects that occurred and the personalised treatment of the patient are also discussed. Finally, the article evaluates current advances in treatment and future therapeutic approaches. This case highlights the challenges of identifying which therapeutic options are most appropriate for individual patients with BRAFV600E metastatic melanoma.

Emergent bilingual children during the silent period: A scoping review of their communication strategies and classroom environments.

This scoping review aimed to investigate the communication strategies utilized by children who acquire a minority language (L1) and subsequently learn a community language (L2) during what is commonly referred to as the "silent period." Electronic database searches were conducted using keywords such as "silent period" and "bilingual children," resulting in the inclusion of 40 studies in the review. The findings revealed that emergent bilingual children utilize various communication strategies, including nonverbal communication, private speech, and their L1, to communicate within classroom environments. The findings shed light on the adaptability of emergent bilingual children during early stage of L2 acquisition. Furthermore, our review provides information about the classroom contexts such as teacher support and peer interactions where children develop their L2 skills. From a clinical perspective, recognizing these strategies and classroom contexts could significantly enhance the screening process for emergent bilingual children.

Nurse-sensitive quality and benchmarking in hospitals striving for Magnet® or Pathway® designation: A qualitative study.

To examine if and how selected German hospitals use nurse-sensitive clinical indicators and perspectives on national/international benchmarking. Qualitative study. In 2020, 18 expert interviews were conducted with key informants from five purposively selected hospitals, being the first in Germany implementing Magnet® or Pathway®. Interviews were analyzed using content analysis with deductive-inductive coding. The study followed the COREQ guideline. Three major themes emerged: first, limited pre-existence of and necessity for nurse-sensitive data. Although most interviewees reported data collection for hospital-acquired pressure ulcers and falls with injuries, implementation varied and interviewees highlighted the necessity to develop additional nurse-sensitive indicators for the German context. Second, the theme creating an enabling data environment comprised building clinicians' acceptance, establishing a data culture, and reducing workload by using electronic health records. Third, challenges and opportunities in establishing benchmarking were identified but most interviewees called for a national or European benchmarking system. The need for further development of nurse-sensitive clinical indicators and its implementation in practice was highlighted. Several actions were suggested at hospital level to establish an enabling data environment in clinical care, including a nationwide or European benchmarking system. Involving nurses in data collection, comparison and benchmarking of nurse-sensitive indicators and their use in practice can improve quality of patient care. Nurse-sensitive indicators were rarely collected, and a need for action was identified. The study results show research needs on nurse-sensitive indicators for Germany and Europe. Measures were identified to create an enabling data environment in hospitals. An initiative was started in Germany to establish a nurse-sensitive benchmarking capacity. Clinical practitioners and nurse/clinical managers were interviewed.

A cross-sectional survey of clinical trials knowledge, participation, and perspectives in an underserved community of Washington, DC.

The inclusion of participants from underrepresented and underserved groups is lagging in dermatology clinical trials. Through dissemination of a pilot survey at a community skin health fair, knowledge, participation, and perspectives of clinical trials were evaluated in an urban, medically underserved community in Washington, DC. Clinical trial-related questions were derived from the Health Information National Trends Survey 5 Cycle 4. This cross-sectional survey analyzed responses from 39/55 attendees (71% response rate). Most respondents were female (23/37 [62.2%]), between the ages of 25 and 54 (19/38, [50.0%]), and self-identified as non-white (35/39 [89.7%]) with a majority self-identifying as Black (16/31 [41%]). Most respondents self-reported knowing "little" to "nothing" about clinical trials (26/35 [74.3%]), and even more were unaware of the federal resource clinicaltrials.gov (30/37 [81.1%]). Few respondents discussed clinical trials as a treatment option with their healthcare provider (8/35 [22.9%]), yet having a discussion was significantly correlated with clinical trial participation (p = 0.0302). Self-reported level of knowledge was not significantly associated with participation in a clinical trial (p = 0.3035). Healthcare providers were the preferred first source of clinical trial information, followed by an internet search. Respondents rarely cited mistrust or skepticism as a barrier to participation (2/34 [5.9%]). Subjective positive healthcare experiences were significantly correlated to positive expectations with clinical trial participation (p = 0.0242). The findings of this study suggest the essential role healthcare providers, including dermatologists, play in clinical trial education and recruitment of underrepresented populations, and that patient mistrust may be present but is a rarely cited barrier to clinical trial participation.

Serum Organophosphorus compound levels as a surrogate marker for severity assessment and management in Acute Organophosphorus Poisoning − A novel approach

Organophosphorus (OP) compounds are the most extensively used pesticides’ class worldwide; cause most self‑poisoning deaths especially in India. Thus, it is utmost important for early identification and aggressive management of OP poisoning from the clinical perspective to prevent serious complications by using sophisticated LC-MS/MS approach. This was a prospective study involving 103 patients of OP cases admitted to Karnataka Institute of Medical Sciences from June 2022 to May 2023, based on the inclusion and exclusion criteria patients were subjected to study. On admission, venous blood was collected from patient with Malathion and Profenofos OP poisoning history and subjected to serum biomarker and to LC-MS/MS analysis. Out of the 103 patients, 68 patients consumed Profenofos (66%) and 35 patients consumed Malathion (34%). Pseudocholinesterase levels among the of OP cases revealed that the 33 patients had mild toxicity, 40 patients had moderate toxicity and 30 patients had severe toxicity of OP poisoning. Subsequently LC-MS/MS analysis showed that the results obtained are not in correlation with indirect serum marker pseudocholinesterase levels. On the other side, LC-MS/MS results are in correlation with the clinical outcome of the patients with respect to morbidity and mortality. Thus, LC-MS/MS approach to assess the OP levels in patients could be used as potential diagnostic and prognostic marker for the absolute quantification of OP compounds compared to indirect OP levels estimation.

#2379 Acute kidney injury as a key predictor of major adverse cardiovascular events in chronic kidney disease patients

Abstract Background and Aims Chronic kidney disease (CKD) significantly raises cardiovascular event risks. The influence of acute-on-chronic kidney incidents is less understood. This study examines the link between acute kidney injury (AKI) episodes and subsequent Major Adverse Cardiovascular Events (MACE) in CKD patients. Method From 2013 to 2016, the CKD-REIN cohort enrolled 3033 adults with CKD stages 3-5 (average age 67; 66% male; mean eGFR 33 mL/min/1.73m²) from 40 French outpatient nephrology clinics, reflecting national geographic and legal diversity. During a 5-year follow-up, all AKI episodes, whether inpatient or outpatient, were identified, confirmed, and categorized per KDIGO-AKI standards by an expert panel. Cardiovascular events were evaluated using clinical trial Cardiovascular and Stroke Endpoint Definitions. MACE cumulative incidences (myocardial infarction, stroke, heart failure hospitalization, cardiovascular death) post-AKI were calculated using Aalen-Johansen methods, accounting for kidney failure and death risks. The impact of the first AKI episode on MACE risk was analyzed using a multivariable Cox model, treating AKI as a time-variable and stratifying by characteristics (in/outpatient status, AKI stage, pre-renal causes, renal recovery at discharge). Factors like demographics, cardiovascular risks, CKD severity, and treatments were considered. Interaction and sensitivity analyses were performed, excluding those with prior AKI or cardiovascular disease. Results During a median follow-up of 5.2 years, 530 patients experienced an incident AKI episode. The cumulative incidence of MACE at 1 year following this initial episode of AKI was 8.1% [95% confidence interval, 6.1; 10.8], with a median time to occurrence of 6.7 months after AKI. After adjustment for multiple confounders, we observed a substantial increased hazard of MACE associated with a first episode of AKI (HR = 5.99 [4.63; 7.76], p &amp;lt; 0.001), and this association remained significant for each MACE component (Fig. 1A). A dose-response relationship was observed, with higher risks in more severe AKI cases (KDIGO grades 2-3) and among hospitalized versus non-hospitalized patients (Fig. 1B). This association was also observed across all subgroups, without any interaction with age, sex, nor major comorbidities (diabetes, history of AKI, or cardiovascular events), as well as in various sensitivity analyses. Overall, we estimated an attributable risk fraction of 18.1% [13.6; 22.4] for MACE associated with AKI episodes within this population. Conclusion Our study highlights a strong dose-response relationship between incident AKI events and the risk of subsequent major cardiovascular events in CKD patients. These findings suggest that AKI may not only be a marker of increased cardiovascular risk but also a potential mediator of this risk. From a clinical perspective, these results underscore the importance of close monitoring and management of AKI in CKD patients to reduce the risk of MACE. This study improves our understanding of the interplay between renal and cardiovascular health, emphasizing the need for integrated care approaches in this high-risk population.

Near-Infrared-II Nanomaterials for Activatable Photodiagnosis and Phototherapy.

Near-Infrared-II (NIR-II) spans wavelengths between 1,000 to 1,700 nanometers, featuring deep tissue penetration and reduced tissue scattering and absorption characteristics, providing robust support for cancer treatment and tumor imaging research. This review explores the utilization of activatable NIR-II photodiagnosis and phototherapy based on tumor microenvironments (e. g., reactive oxygen species, pH, glutathione, hypoxia) and external stimulation (e. g., laser, ultrasound, photothermal) for precise tumor treatment and imaging. Special emphasis is placed on the advancements and advantages of activatable NIR-II nanomedicines in novel therapeutic modalities like photodynamic therapy, photothermal therapy, and photoacoustic imaging. This encompasses achieving deep tumor penetration, real-time monitoring of the treatment process, and obtaining high-resolution, high signal-to-noise ratio images even at low material concentrations. Lastly, from a clinical perspective, the challenges faced by activatable NIR-II phototherapy are discussed, alongside potential strategies to overcome these hurdles.