Monitoring Treatment Efficacy Research Articles

Bioelectrical Impedance Vector Analysis, Nutritional Ultrasound®, and Handgrip Strength as Innovative Methods for Monitoring Critical Anorexia Nervosa Physical Recovery: A Pilot Study.

Eating disorders (EDs) manifest as persistent disruptions in eating habits or related behaviors, significantly impacting physical health and psychosocial well-being. Nutritional assessment in ED patients is crucial for monitoring treatment efficacy. While dual-energy X-ray absorptiometry (DEXA) remains standard, interest in alternative methods such as bioelectrical impedance vector analysis (BIVA) and Nutritional Ultrasound® (NU) has risen due to their affordability and portability. Additionally, hand dynamometry offers a user-friendly approach to assessing grip strength (HGS), indicative of nutritional status. A prospective study was carried out to evaluate the utility of BIVA, NU®, and HGS in 43 female AN patients. Measurements were taken at baseline and hospital discharge. A total of 41 patients completed the study. After the intervention, numerous BIVA-related parameters such as fat (3.5 ± 2 kg vs. 5.3 ± 2.7 kg, p < 0.001) and free fat mass (33.9 ± 3.8 kg vs. 37.5 ± 4.1 kg, p < 0.001) were partially restored. Similarly, Nutritional Ultrasound® showed promising results in assessing body composition changes such as total abdominal fat tissue (0.5 ± 0.3 cm vs. 0.9 ± 0.3 cm, p < 0.05). In the same way, rectus femoris cross-sectional area values correlated with clinical outcomes such as free fat mass (0.883, p < 0.05) and appendicular muscle mass (0.965, p < 0.001). HGS reached the normality percentile after the intervention (21.6 ± 9.1 kg vs. 25.9 ± 12.3 kg, p < 0.05), demonstrating a significant association between grip strength and body composition parameters such as free fat mass (0.658, p < 0.001) and appendicular muscle mass (0.482, p < 0.001). Incorporating BIVA-, NU®-, and HGS-enhanced nutritional assessment into the treatment of AN patients offers cost-effective, portable, and non-invasive alternatives to DEXA. These techniques offer valuable insights into changes in body composition and nutritional status, which, in turn, facilitate treatment monitoring and contribute to improved patient outcomes.

Abstract A023: Stratification of bladder cancer patients with the use of flow cytometry is increasing the diagnostic potential of molecular classifiers

Abstract Recent research suggests the potential categorization of bladder cancer (BLCa) patients into molecular subtypes to aid in the selection of appropriate treatment strategies, be it conventional, targeted, or a combination thereof. However, the practical implementation of molecular classifiers has faced obstacles due to the intricate nature of gene regulation, tumor heterogeneity, and challenges related to tumor sampling caused by substantial stromal infiltration and tumor multifocality. Hence, there is a pressing need for more straightforward marker-based methodologies to assist in genomic and transcriptomic subtyping efforts. Our study addressed this gap by establishing and validating a panel of antibodies for application in flow cytometry (FCM) to enhance the stratification of BLCa patients. We curated a set of 17 FCM markers capable of delineating four cell clusters (epithelial, immune, endothelial, and stromal) and defining tumor classification (basal and luminal), immune infiltration, and hot-target expression on BLCa tissue samples. This FCM panel was deployed on ex vivo tissue samples treated with chemotherapy and targeted therapy agents. Initially tested on a cohort of 10 BLCa tissue samples, our validation of the FCM panel revealed correlations between marker expression and clinical-pathological features, such as the presence of metastasis and heightened immune and stromal infiltration. Notably, samples exhibiting lower claudin-4 levels displayed increased immune infiltration, while those with metastases at diagnosis showcased elevated basal marker expression. The translational potential of the FCM panel was demonstrated in ex vivo experiments where tissue slices from six patients were subjected to chemotherapy and targeted therapy agents, leading to observable shifts in marker expression post-treatment, particularly pronounced with chemotherapy. Noteworthy effects included reductions in epithelial cells expressing FGFR3 and EGFR following targeted therapy with erdafitinib or lapatinib, alongside alterations in the basal/luminal cell ratio indicated by increased CD44, CD90, and CD239 marker expressions. Our findings underscore the value of FCM in categorizing BLCa patients based on specific marker expression, supplementing conventional histological analyses to enhance cancer diagnosis, guide personalized therapeutic approaches, and monitor treatment efficacy. Citation Format: Martina Radic, Federico La Manna, Martina Minoli, Panagiotis Chouvardas, George N. Thalmann, Roland Seiler-Blarer, Marianna Kruithof-de Julio, Bernhard Kiss. Stratification of bladder cancer patients with the use of flow cytometry is increasing the diagnostic potential of molecular classifiers [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A023.

Trichoscopic and Clinico-Morphological Evaluation of Tinea Capitis

Abstract Introduction: Tinea capitis (TC) is a common fungal infection of the scalp, especially in children. Trichoscopy is a noninvasive technique that allows rapid and magnified in vivo observation of the hair with the visualization of morphologic features that are often imperceptible to the naked eye. Aim: This study aimed to evaluate the usefulness of trichoscopy in clinical diagnosis and to study various clinico-morphological patterns of TC. Materials and Methods: This cross-sectional, observational study included 140 clinically diagnosed cases of TC seen during a period of 1 year (April 2021 to March 2022). All patients were evaluated using a dermoscope (DermLite DL4 Multispectral 3 Gen, San Juan Capistrano, CA, USA,10×). Results: The prevalence rate of TC in this study was 2.69 per thousand population. The most common clinical variant was gray patch followed by kerion and black dot, and the most common etiological agent was Trichophyton tonsurans. The characteristic trichoscopic features were as follows: comma hairs (80%), followed by corkscrew hairs (68.6%), bent hairs (54.2%), zigzag hairs (35.7%), and morse code-like hairs (15%). Other findings included scaling (89.2%), followed by black dot (67.1%), broken hairs (42.8%), and crusting and pustules (32.1% each). Comma and corkscrew-shaped hairs were most common in the black dot type, whereas zigzag, bent hairs, and morse code hairs were common in the gray patch type of TC. There was a significant association between trichoscopic findings and type of TC. Conclusion: Trichoscopy can be considered a novel tool for rapid diagnosis and selection of the appropriate therapy and in the monitoring of treatment efficacy in TC.

Metabolomics assisted by transcriptomics analysis to reveal metabolic characteristics and potential biomarkers associated with treatment response of neoadjuvant therapy with TCbHP regimen in HER2 + breast cancer

BackgroundThis study aimed to explore potential indicators associated with the neoadjuvant efficacy of TCbHP regimen (taxane, carboplatin, trastuzumab, and pertuzumab) in HER2 + breast cancer (BrCa) patients.MethodsA total of 120 plasma samples from 40 patients with HER2 + BrCa were prospectively collected at three treatment times of neoadjuvant therapy (NAT) with TCbHP regimen. Serum metabolites were analyzed based on LC-MS and GC-MS data. Random forest was used to establish predictive models based on pre-therapeutic differentially expressed metabolites. Time series analysis was used to obtain potential monitors for treatment response. Transcriptome analysis was performed in nine available pre‑therapeutic specimens of core needle biopsies. Integrated analyses of metabolomics and transcriptomics were also performed in these nine patients. qRT-PCR was used to detect altered genes in trastuzumab-sensitive and trastuzumab-resistant cell lines.ResultsTwenty-one patients achieved pCR, and 19 patients achieved non-pCR. There were significant differences in plasma metabolic profiles before and during treatment. A total of 100 differential metabolites were identified between pCR patients and non-pCR patients at baseline; these metabolites were markedly enriched in 40 metabolic pathways. The area under the curve (AUC) values for discriminating the pCR and non-PCR groups from the NAT of the single potential metabolite [sophorose, N-(2-acetamido) iminodiacetic acid, taurine and 6-hydroxy-2-aminohexanoic acid] or combined panel of these metabolites were greater than 0.910. Eighteen metabolites exhibited potential for monitoring efficacy. Several validated genes might be associated with trastuzumab resistance. Thirty-nine altered pathways were found to be abnormally expressed at both the transcriptional and metabolic levels.ConclusionSerum-metabolomics could be used as a powerful tool for exploring informative biomarkers for predicting or monitoring treatment efficacy. Metabolomics integrated with transcriptomics analysis could assist in obtaining new insights into biochemical pathophysiology and might facilitate the development of new treatment targets for insensitive patients.

Total metabolic tumor volume on 18F-FDG PET/CT is a game-changer for patients with metastatic lung cancer treated with immunotherapy

PurposeBecause of atypical response imaging patterns in patients with metastatic non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICPIs), new biomarkers are needed for a better monitoring of...

Memory impairment in Amyloidβ-status Alzheimer's disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T

IntroductionIn Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI). MethodsWe used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidβ-status AD and 18 age-matched controls, with respective age ranges of 60 (42–76) and 62 (52–79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study. ResultsA significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory. DiscussionThis study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy. ClinicalTrials.govID NCT04992975 (Clinicaltrial.gov 2023)

Abstract 5027: Simplified selective electrochemical detection of ctDNA differentiates between cancer progression and regression

Abstract Advanced cancers therapies, including personalized ones, often fail. Rapid evaluation of treatment efficacy is therefore critical to reduce medical and financial side effects and, most importantly, facilitate the implementation of a therapy most appropriate for that individual. Current approaches for evaluating treatment are too slow and expensive to rapidly modify therapy. The previously documented selective affinity of DNA to Au surfaces, albeit cumbersome, unsuitable for point-of-care (PoC) applications and having poor discrimination ability, suggested a solution to this clinically important problem. Methods presented herein potentially solve the problem as first illustrated by a studies of plasma from those with and without cancers. Multiple improvements, most notably optimized buffer conditions dramatically changed and enhanced the difference in adsorption between ctDNA and normal cfDNA drastically improving assay performance. The enhanced sensitivity of this Therascape™ assay was not only able to better detect the difference between healthy and cancer cfDNA but demonstrated potential for the monitoring of cancer treatment efficacy. De-identified clinical samples of the few patients that the Scripps Biorepository and University of Colorado supplied had samples before and after treatment, and were known to have progressed or responded in the interim, were analyzed. This initial group included 6 lymphoma patients and two NSCLC patients (in one case the cfDNA was isolated from urine). One of the patient samples taken before initiating therapy was in the healthy range and considered ineligible for the assay. Ten before and after pairs were then evaluated in a blinded fashion. TheraScape correctly correlated with the change in cancer burden in each pair (10/10 times, p = 0.00016, paired t-test). In some cases the “after” specimen was ~1 month after therapy began. The presentation will include additional patients. The CVs of repeat electrodes were less than 10%, interoperator variability did not increase this. The novel method of detecting cfDNA using disposable electrodes presents a significant advancement in monitoring the efficacy of treatments for advanced cancers, and may be particularly critical for immunotherapy. This approach reduced expenses by 10 to 50 times compared to current reimbursement rates for sequence dependent methods, even more critical is the same day turn around would allow rapid, truly individualized, patient therapy optimization. Citation Format: Matthew Jordan Russo, Kirsten Arnold, Shannon Tunney, Suzin Wright, Floyd Taub, Charles S. Henry. Simplified selective electrochemical detection of ctDNA differentiates between cancer progression and regression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5027.

Abstract 7503: Non-clinical study of circulating tumor cells in humanized mice: Post-xenograft effects in immunodeficient mice

Abstract Circulating tumor cells (CTCs) possess the potential to serve as innovative markers in clinical trials, contributing to the understanding of cancer metastasis mechanisms, diagnosis, prognosis, the development of personalized treatment strategies, and enabling the monitoring of treatment efficacy. NSG mice, which are a strain of immunodeficient mice frequently utilized as a non-clinical model for cancer research, exhibit diminished levels of natural killer (NK) cells and abnormal monocytes in their bloodstream. In a previous study, a positive correlation was observed between the duration of injection and the levels of white blood cells (WBC) in mice that were injected with various cancer cell lines derived from humans. To evaluate the correlation among the primary tumor and circulating tumor cells (CTCs), as well as the impact on immune cells, we assessed changes in immune cell composition, primary tumor size, and enumeration of CTCs in xenografted mice over a period of time. This investigation was carried out using CytoGen's Smart Biopsy™ systems. The results, which were obtained using equipment including CytoGen's Smart Biopsy™ Systems, showed that the distribution of white blood cell (WBC) components exhibited variations based on age, primary tumor burden, and circulating tumor cell (CTC) count following injection. A notable association was observed between the augmentation of immune cells and the quantity of circulating tumor cells (CTCs) present in the bloodstream. Therefore, alterations in immune cells may potentially impact the potential to affect the ability to influence the efficacy of cancer immunotherapy, metabolic therapy, and anti-metastatic therapy. When conducting non-clinical investigations with the objective of developing cancer treatment protocols, it is crucial to meticulously select humanized or immunodeficient mice that are appropriate for the study. Therefore, it is advisable to perform regular monitoring of murine blood samples in order to observe any variations in the counts of circulating tumor cells (CTCs), while considering a standardized blood volume per individual. In the immunodeficient mouse model, the existence of circulating tumor cells (CTCs) results in an increase in the quantity of cells present in the bloodstream. The observed rise in circulating tumor cells (CTCs) is found to be concurrent with the progression and development of the primary tumor. The consideration of this aspect is of utmost importance in the formulation of non-clinical studies aimed at the development of cancer treatment protocols. Citation Format: Sehyung Pak, Hajin Pak, Hee Jin Yoo, Sra Min, Hui Ji Kim, JaeYoon Lee, Min-Ji Song, Jaesung Choi, Aejin Jeong, Hanbyeol Kim, Jung Won Kim, Hai-Chon Lee. Non-clinical study of circulating tumor cells in humanized mice: Post-xenograft effects in immunodeficient mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7503.

Abstract 3637: Ultrasensitive assays for combined detection of CEA+ extracellular vesicles and soluble CEA

Abstract Colorectal cancer (CRC) is the third most common cancer worldwide and is the second leading cause of cancer death in the United States. Carcinoembryonic antigen (CEA) is a biomarker commonly used in the management of CRC. It is typically present at low levels in the blood of healthy adults but is elevated in CRC samples and some other cancers. CEA is most commonly used to monitor treatment efficacy and as a critical part of post-treatment surveillance for residual disease, recurrence, and/or progression/metastasis. The CRC recurrence rate averages &amp;gt;25%, and liver metastasis occurs in 25-30% of cases. Improved CEA assays could enable earlier determination of treatment failure, detection of lower levels of minimal residual disease (MRD) after treatment, or earlier detection of recurrence. CEA is a GPI-linked membrane protein secreted from CRC cells mainly by enzymatic cleavage of its GPI anchor. However, we have identified alternative secretion of CEA in association with extracellular vesicles (EVs). We hypothesized that the soluble CEA produced by canonical shedding and the alternatively secreted CEA may provide distinct information about the tumor or its microenvironment and serve as independent but complementary biomarkers of CRC. We developed ultrasensitive, multi-marker electrochemiluminescence (ECL) immunoassays for measuring intact EVs presenting CEA, CD73, or both in human plasma. We observed that plasma levels of CEA+EVs and CD73+EVs were elevated in some late-stage CRC samples compared to controls. CEA and CD73 double-positive EV (CEA+CD73+EVs) levels were also elevated in the same samples, exhibiting a 3-fold improved separation of these samples with CRC from controls, compared to detection of CEA+EVs. Additionally, approximately 25% of stage IV CRC samples had elevated CEA+EV and CEA+CD73+EV levels while exhibiting low soluble CEA. We confirmed this result in an independent sample set that included samples across all CRC stages, and also identified a few earlier-stage samples that exhibited high CEA+EVs and CEA+CD73+EVs without elevated soluble CEA. Since CEA+CD73+EVs and soluble CEA assays identified different subsets of samples, we combined the two assays into a single classifier for late stage CRC and controls, yielding improved receiver operator characteristic (ROC) with area under the curve (AUC) of 0.975 versus 0.927 for the standard soluble CEA assay or 0.788 for CEA+CD73+EVs alone. These results suggest that assaying EVs presenting multiple surface markers can increase specificity for the detection of tumor-derived EVs relative to a single marker and that assaying both soluble and EV-associated forms of CEA in plasma may improve the value of CEA measurement in CRC. Citation Format: Lucie Hebert, Misk Al-Ameen, Talis Spriggs, Collin Nelson, Evan A. Gizzie, Jeffrey L. Franklin, Robert J. Coffey, David A. Routenberg, Jacob N. Wohlstadter. Ultrasensitive assays for combined detection of CEA+ extracellular vesicles and soluble CEA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3637.

Cell‐free DNA‐associated multi‐feature applications in cancer diagnosis and treatment

AbstractMalignant tumours pose significant challenges in terms of high morbidity and mortality rates, primarily due to the lack of large‐scale applicable screening methods and efficient treatment strategies. However, the development of liquid biopsies, particularly circulating cell‐free DNA (cfDNA), offers promising solutions characterised by their non‐invasiveness and cost‐effectiveness, providing comprehensive tumour information on a global scale. The release of cfDNA is predominantly associated with cell death and turnover, while its elimination occurs through nuclease digestion, renal excretion into the urine and uptake by the liver and spleen. Extensive research into the biological properties of cfDNA has led to the identification of novel applications, including non‐invasive cancer screening, cancer subtype classification, tissue‐of‐origin detection and monitoring of treatment efficacy. Additionally, emerging fields such as methylation‐omics, fragment‐omics and nucleosome‐omics show immense potential as tissue‐ and disease‐specific markers. Therefore, this review aims to comprehensively introduce the latest detection techniques of cfDNA, along with detailed information on its characteristics and applications, providing valuable insights for cancer diagnosis and monitoring, which will assist us in purposefully enhancing relevant features for a more comprehensive application in clinical practice.

Complement Blockade, a New Therapeutic Approach in Malignant Hypertension

Abstract Atypical hemolytic uremic syndrome (aHUS) represents a major challenge due to its rare nature and severe impact on patients, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. This paper describes the case of a 41-year-old patient diagnosed with aHUS in the context of malignant arterial hypertension and severe renal impairment, manifested by anuria and significant azotemic retention syndrome. The complex management of the case, including the use of Eculizumab, a complement inhibitor, highlighted significant therapeutic benefits, especially in improving hematological parameters. Despite a positive response, challenges related to dosing, monitoring treatment efficacy, and maintaining remission without relapses emphasize the need for adapted therapeutic strategies and a deeper understanding of the disease mechanisms. This case also highlights the importance of individualized approaches and consideration of the possible benefits of dose adjustments based on specific clinical and pharmacological parameters, as well as continuous evaluation of treatment efficacy and safety, in the context of such a variable and potentially devastating syndrome as aHUS.

Hyperpolarized Xenon-129 Chemical Exchange Saturation Transfer (HyperCEST) Molecular Imaging: Achievements and Future Challenges.

Molecular magnetic resonance imaging (MRI) is an emerging field that is set to revolutionize our perspective of disease diagnosis, treatment efficacy monitoring, and precision medicine in full concordance with personalized medicine. A wide range of hyperpolarized (HP) 129Xe biosensors have been recently developed, demonstrating their potential applications in molecular settings, and achieving notable success within in vitro studies. The favorable nuclear magnetic resonance properties of 129Xe, coupled with its non-toxic nature, high solubility in biological tissues, and capacity to dissolve in blood and diffuse across membranes, highlight its superior role for applications in molecular MRI settings. The incorporation of reporters that combine signal enhancement from both hyperpolarized 129Xe and chemical exchange saturation transfer holds the potential to address the primary limitation of low sensitivity observed in conventional MRI. This review provides a summary of the various applications of HP 129Xe biosensors developed over the last decade, specifically highlighting their use in MRI. Moreover, this paper addresses the evolution of in vivo applications of HP 129Xe, discussing its potential transition into clinical settings.

Diagnostic and prognostic value of biomarkers in atopic dermatitis for assessing its endotypes, phenotypes, and treatment efficacy

Atopic dermatitis is a highly heterogeneous disease that usually requires a tailored approach to therapy. Recent studies have described a variety of biomarkers linked to diverse pathophysiological aspects of atopic dermatitis. Furthermore, they have provided encouraging evidence supporting high clinical importance of these biomarkers as promising tools for personalized diagnosis, assessment of disease severity, and monitoring of treatment efficacy. This review aims to provide a comprehensive summary of research progress on atopic dermatitis biomarkers, their diagnostic and prognostic value, as well as the benefits they might potentially offer not only for determining the disease endotype, but also for developing novel management strategies. The implementation of easily accessible and simple methods to measure atopic dermatitis biomarkers into clinical practice is an ambitious task for allergologists and dermatologists. A detailed overview of currently available data will allow us to identify the most important trajectories for future research in this area that will promote the concept of personalized atopic dermatitis therapy, reduce the disease burden, and improve the quality of life of patients.

Molecular monitoring of treatment efficacy in human visceral leishmaniasis.

Focused efforts of the visceral leishmaniasis elimination program have led to a drastic decline in cases, and the present challenge is disease monitoring, which this study aimed to assess. A Leishmania kinetoplastid-targeted qPCR quantified parasite load at disease presentation, and following treatment completion (n=49); an additional 80 cases were monitored after completion of treatment. The parasite load at disease presentation was 13 461.00 (2560.00-37764.00)/µg gDNA, which upon completion of treatment reduced in 47 of 49 cases to 1(1-1)/µg gDNA, p<0.0001. In 80 cases that presented >2 months post-treatment, their parasite burden similarly decreased to 1(1-1)/µg gDNA except in 6 of 80 cases, which were qPCR positive. In 129 cases of visceral leishmaniasis, qPCR by quantification of parasite burden proved effective for monitoring treatment.

Evaluating an EEG-based tool for assessing acute clinical and cognitive changes in adult outpatients with MDD treated with open-label, flexible-dose vortioxetine: A pilot study

BackgroundIdentifying neurological biomarkers to aid with diagnoses and treatment effect evaluation of mood and cognitive symptoms in major depressive disorder (MDD) is an unmet need. This study explores the Brain Network Analytics (BNA) tool, which provides information on cortical patterns compared to a healthy normative group, for improving MDD management. MethodsBNA was used to extract event-related potentials (ERPs) from high-density EEG, and its clinical utility to assess the effects of vortioxetine on depression and cognition was evaluated. Twenty-five MDD subjects (20–65 years old) with cognitive dysfunction underwent an 8-week open-label treatment using vortioxetine. ERP data, generated during cognitive tasks, were collected at pre-treatment, two weeks and eight weeks into treatment. Correlations with MDD symptoms and cognitive functioning were investigated. Exploratory analyses assessed the differences in baseline and endpoint ERP characteristics between MDD subjects and matched controls (N = 41). ResultsCompared to controls, MDD subjects exhibited increased baseline latencies of P200 and P3b ERP components, which normalized at treatment endpoint. P200 and P300 in the MDD group were correlated with clinical assessments, and indicated a pro-cognitive effect of vortioxetine independent of its antidepressant effect. LimitationsThis study was limited by a small sample size and lack of a placebo condition. ConclusionsOur results suggest that the application of BNA can potentially support MDD diagnosis and monitor treatment efficacy across various symptom and functional domains. Further studies are warranted to explore the role of BNA in clinical research and practice.

Machine Learning in the Parkinson’s disease smartwatch (PADS) dataset

The utilisation of smart devices, such as smartwatches and smartphones, in the field of movement disorders research has gained significant attention. However, the absence of a comprehensive dataset with movement data and clinical annotations, encompassing a wide range of movement disorders including Parkinson’s disease (PD) and its differential diagnoses (DD), presents a significant gap. The availability of such a dataset is crucial for the development of reliable machine learning (ML) models on smart devices, enabling the detection of diseases and monitoring of treatment efficacy in a home-based setting. We conducted a three-year cross-sectional study at a large tertiary care hospital. A multi-modal smartphone app integrated electronic questionnaires and smartwatch measures during an interactive assessment designed by neurologists to provoke subtle changes in movement pathologies. We captured over 5000 clinical assessment steps from 504 participants, including PD, DD, and healthy controls (HC). After age-matching, an integrative ML approach combining classical signal processing and advanced deep learning techniques was implemented and cross-validated. The models achieved an average balanced accuracy of 91.16% in the classification PD vs. HC, while PD vs. DD scored 72.42%. The numbers suggest promising performance while distinguishing similar disorders remains challenging. The extensive annotations, including details on demographics, medical history, symptoms, and movement steps, provide a comprehensive database to ML techniques and encourage further investigations into phenotypical biomarkers related to movement disorders.

MONITORING IN VITRO AND EX VIVO INFLAMMATION USING SINGLE-WALLED CARBON NANOTUBES (SWCNTS) SENSOR TECHNOLOGY

Osteoarthritis (OA) is a degenerative joint disease affecting millions worldwide. Early detection of OA and monitoring its progression is essential for effective treatment and for preventing irreversible damage. Although sensors have emerged as a promising tool for monitoring analytes in patients, their application for monitoring the state of pathology is currently restricted to specific fields (such as diabetes). In this study, we present the development of an optical sensor system for real-time monitoring of inflammation based on the measurement of nitric oxide (NO), a molecule highly produced in tissues during inflammation.Single-walled carbon nanotubes (SWCNT) were functionalized with a single-stranded DNA (ssDNA) wrapping designed using an artificial intelligence approach and tested using S-nitroso-N-acetyl penicillamine (SNAP) as a standard released-NO marker. An optical SWIR reader with LED excitation at 650 nm, 730 nm and detecting emission above 1000 nm was developed to read the fluorescence signal from the SWCNTs. Finally, the SWCNT was embedded in GelMa to prove the feasibility of monitoring the release of NO in bovine chondrocyte and osteochondral inflamed cultures (1–10 ng/ml IL1β) monitored over 48 hours. The stability of the inflammation model and NO release was indirectly validated using the Griess and DAF-FM methods. A microfabricated sensor tag was developed to explore the possibility of using ssDNA-SWCNT in an ex vivo anatomic set-up for surgical feasibility, the limit of detection, and the stability under dynamic flexion.The SWCNT sensor was sensitive to NO in both in silico and in vitro conditions during the inflammatory response from chondrocyte and osteochondral plug cultures. The fluorescence signal decreased in the inflamed group compared to control, indicating increased NO concentration. The micro-tag was suitable and stable in joints showing a readable signal at a depth of up to 6 mm under the skin.The ssDNA-SWCNT technology showed the possibility of monitoring inflammation continuously in an in vitro set-up and good stability inside the joint. However, further studies in vivo are needed to prove the possibility of monitoring disease progression and treatment efficacy in vivo.Acknowledgments: The project was co-financed by Innosuisse (grant nr. 56034.1 IP-LS)

Clinical associations of corneal neuromas with ocular surface diseases.

Corneal neuromas, also termed microneuromas, refer to microscopic, irregularly-shaped enlargements of terminal subbasal nerve endings at sites of nerve damage or injury. The formation of corneal neuromas results from damage to corneal nerves, such as following corneal pathology or corneal or intraocular surgeries. Initially, denervated areas of sensory nerve fibers become invaded by sprouts of intact sensory nerve fibers, and later injured axons regenerate and new sprouts called neuromas develop. In recent years, analysis of corneal nerve abnormalities including corneal neuromas which can be identified using in vivo confocal microscopy, a non-invasive imaging technique with microscopic resolution, has been used to evaluate corneal neuropathy and ocular surface dysfunction. Corneal neuromas have been shown to be associated with clinical symptoms of discomfort and dryness of eyes, and are a promising surrogate biomarker for ocular surface diseases, such as neuropathic corneal pain, dry eye disease, diabetic corneal neuropathy, neurotrophic keratopathy, Sjögren's syndrome, bullous keratopathy, post-refractive surgery, and others. In this review, we have summarized the current literature on the association between these ocular surface diseases and the presentation of corneal microneuromas, as well as elaborated on their pathogenesis, visualization via in vivo confocal microscopy, and utility in monitoring treatment efficacy. As current quantitative analysis on neuromas mainly relies on manual annotation and quantification, which is user-dependent and labor-intensive, future direction includes the development of artificial intelligence software to identify and quantify these potential imaging biomarkers in a more automated and sensitive manner, allowing it to be applied in clinical settings more efficiently. Combining imaging and molecular biomarkers may also help elucidate the associations between corneal neuromas and ocular surface diseases.

Does Speckle Tracking Transthoracic Echocardiography Indicate Subtle Changes in Left Ventricular Function in Heart Failure Patients with Reduced Ejection Fraction Treated by Sacubitril-valsartan?

Abstract Background: In heart failure patients and reduced ejection fraction (HFrEF), assessing subtle changes in left ventricle (LV) function is crucial for monitoring treatment efficacy. This study aims to determine the effect of valsartan/sacubitril on LV ejection fraction (EF) assessed by two-dimensional (2D) transthoracic echocardiography (TTE) in comparison to that assessed by 2D TTE speckle tracking in patients with HFrEF ≤35% after 6 months of treatment. Patients and Methods: A prospective study will be conducted on 200 heart failure patients with reduced EF (HFrEF) undergoing sacubitril-valsartan treatment. Each participant underwent a comprehensive evaluation, including physical examination, history taking, serial 12-lead electrocardiogram, and 2D echo to evaluate cardiac parameters. In addition, 2D speckle tracking echocardiography (STE) assessments were conducted before and after 6 months of valsartan/sacubitril treatment. Results: The enrolled patients had an average age of 48 years with 63% females. At the beginning of the study, 9 (4.5%) patients were classified as New York Heart Association (NYHA) FC I, 120 (60%) as NYHA FC II, 64 (32%) as NYHA FC III, and 7 (3.5%) as FC IV. Following treatment, 82 (41%) patients improved to NYHA FC I, and 118 (59%) were in NYHA FC II. Notably, 82 (41%) patients showed improved left ventricular EF (LVEF), detected either by traditional TTE or STE, whereas 118 (59%) showed no improvement in EF through traditional TTE. In addition, 74 (37%) patients demonstrated improvement detected by STE. In contrast, 44 (22%) patients demonstrated no improvement in EF detected by either TTE or STE. Conclusion: STE was a more reliable diagnostic method for seeing early LVEF improvement in patients with HFrEF receiving valsartan/sacubitril treatment not seen by conventional TTE.

Nanomedicine as a multimodal therapeutic paradigm against cancer: on the way forward in advancing precision therapy.

Recent years have witnessed dramatic improvements in nanotechnology-based cancer therapeutics, and it continues to evolve from the use of conventional therapies (chemotherapy, surgery, and radiotherapy) to increasingly multi-complex approaches incorporating thermal energy-based tumor ablation (e.g. magnetic hyperthermia and photothermal therapy), dynamic therapy (e.g. photodynamic therapy), gene therapy, sonodynamic therapy (e.g. ultrasound), immunotherapy, and more recently real-time treatment efficacy monitoring (e.g. theranostic MRI-sensitive nanoparticles). Unlike monotherapy, these multimodal therapies (bimodal, i.e., a combination of two therapies, and trimodal, i.e., a combination of more than two therapies) incorporating nanoplatforms have tremendous potential to improve the tumor tissue penetration and retention of therapeutic agents through selective active/passive targeting effects. These combinatorial therapies can correspondingly alleviate drug response against hypoxic/acidic and immunosuppressive tumor microenvironments and promote/induce tumor cell death through various multi-mechanisms such as apoptosis, autophagy, and reactive oxygen-based cytotoxicity, e.g., ferroptosis, etc. These multi-faced approaches such as targeting the tumor vasculature, neoangiogenic vessels, drug-resistant cancer stem cells (CSCs), preventing intra/extravasation to reduce metastatic growth, and modulation of antitumor immune responses work complementary to each other, enhancing treatment efficacy. In this review, we discuss recent advances in different nanotechnology-mediated synergistic/additive combination therapies, emphasizing their underlying mechanisms for improving cancer prognosis and survival outcomes. Additionally, significant challenges such as CSCs, hypoxia, immunosuppression, and distant/local metastasis associated with therapy resistance and tumor recurrences are reviewed. Furthermore, to improve the clinical precision of these multimodal nanoplatforms in cancer treatment, their successful bench-to-clinic translation with controlled and localized drug-release kinetics, maximizing the therapeutic window while addressing safety and regulatory concerns are discussed. As we advance further, exploiting these strategies in clinically more relevant models such as patient-derived xenografts and 3D organoids will pave the way for the application of precision therapy.