Therapy For Disease Research Articles

Consensus Statements on Assessments and Vaccinations Prior to Commencement of Advanced Therapies for the Treatment of Inflammatory Bowel Diseases.

Given the introduction of new advanced therapies for inflammatory bowel diseases (IBDs), expanded risk mitigation strategies are essential. To create a comprehensive set of statements on assessment procedures and vaccinations before starting monoclonal antibodies, Janus kinase (JAK) inhibitors or sphingosine-1-phosphate (S1P) modulators for IBD. We examined literature, guidelines and drug product information regarding vaccination and assessment recommendations for initiating advanced IBD therapies. Using a modified Delphi approach, delegates voted anonymously on the acceptability of these statements prior to and following consensus discussion. We developed eight statements on the domains of infectious diseases screening, vaccinations and assessments prior to commencing JAK inhibitors and S1P modulators. Six statements received agreement. Pre-advanced therapy screening for infectious diseases was established, and the vaccination protocol was revised. Malignancy, cardiovascular and thromboembolic risk assessments are necessary before initiating JAK inhibitors. Those starting S1P modulators need cardiac and ophthalmic assessments. These consensus statements combine vaccination and assessments on the currently available advanced therapies for IBD as a single comprehensive document that may reduce IBD complications associated with use of advanced therapies. Knowledge gaps identified during the consensus process will provide further research opportunities.

Investigation of local stimulation effects of embedding PGLA at Zusanli (ST36) acupoint in rats based on TRPV2 and TRPV4 ion channels

IntroductionAcupoint Catgut Embedding (ACE) is an extended and developed form of traditional acupuncture that serves as a composite stimulation therapy for various diseases. However, its local stimulation effects on acupoints remain unclear. Acupuncture can activate mechanically sensitive calcium ion channels, TRPV2 and TRPV4, located on various cell membranes, promoting Ca2+ influx in acupoint tissues to exert effects. Whether ACE can form mechanical physical stimulation to regulate these channels and the related linkage effect requires validation.MethodsThis study investigates the influence of TRPV2 and TRPV4 ion channels on the local stimulation effects of ACE by embedding PGLA suture at the Zusanli (ST36) acupoint in rats and using TRPV2 and TRPV4 inhibitors. Flow cytometry, immunofluorescence, Western blot, and Real-time quantitative PCR were employed to detect intracellular Ca2+ fluorescence intensity, the expression of macrophage (Mac) CD68 and mast cell (MC) tryptase, as well as the protein and mRNA expression of TRPV2 and TRPV4 in acupoint tissues after PGLA embedding.ResultsThe results indicate that ACE using PGLA suture significantly increases the mRNA and protein expression of TRPV2 and TRPV4, Ca2+ fluorescence intensity, and the expression of Mac CD68 and MC tryptase in acupoint tissues, with these effects diminishing over time. The increasing trends are reduced after using inhibitors, particularly when both inhibitors are used simultaneously. Furthermore, correlation analysis shows that embedding PGLA suture at the ST36 acupoint regulates Mac and MC functions through Ca2+ signaling involving not only TRPV2 and TRPV4 but multiple pathways.DiscussionThese results suggest that embedding PGLA suture at the ST36 acupoint generates mechanical physical stimulation and regulates TRPV2 and TRPV4 ion channels, which couple with Ca2+ signaling to form a linkage effect that gradually weakens over time. This provides new reference data for further studies on the stimulation effects and clinical promotion of ACE.

Application of novel CAR technologies to improve treatment of autoimmune disease

Chimeric antigen receptor (CAR) T cell therapy has become an important treatment for hematological cancers, and its success has spurred research into CAR T cell therapies for other diseases, including solid tumor cancers and autoimmune diseases. Notably, the development of CAR-based treatments for autoimmune diseases has shown great progress recently. Clinical trials for anti-CD19 and anti-BCMA CAR T cells in treating severe B cell-mediated autoimmune diseases, like systemic lupus erythematosus (SLE), have shown lasting remission thus far. CAR T cells targeting autoreactive T cells are beginning clinical trials for treating T cell mediated autoimmune diseases. Chimeric autoantigen receptor (CAAR) T cells specifically target and eliminate only autoreactive B cells, and they have shown promise in treating mucosal pemphigus vulgaris and MuSK myasthenia gravis. Regulatory CAR T cells have also been developed, which show potential in altering autoimmune affected areas by creating a protective barrier as well as helping decrease inflammation. These new treatments are only the beginning of potential CAR T cell applications in treating autoimmune disease. Novel CAR technologies have been developed that increase the safety, potency, specificity, and efficacy of CAR T cell therapy. Applying these novel modifications to autoimmune CARs has the potential to enhance the efficacy and applicability of CAR therapies to autoimmune disease. This review will detail several recently developed CAR technologies and discuss how their application to autoimmune disease will improve this emerging field. These include logic-gated CARs, soluble protein-secreting CARs, and modular CARs that enable CAR T cell therapies to be more specific, reach a wider span of target cells, be safer for patients, and give a more potent cytotoxic response. Applying these novel CAR technologies to the treatment of autoimmune diseases has the potential to revolutionize this growing application of CAR T cell therapies.

A phase III, open-label clinical trial evaluating pegunigalsidase alfa administered every 4 weeks in adults with Fabry disease previously treated with other enzyme replacement therapies.

Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

Invasive Fungal Infections in Immunocompromised Conditions: Emphasis on COVID-19.

The COVID-19 pandemic caused death of 6 million lives globally, primarily from respiratory failure, but also a significant number from invasive fungal co-infections in these patients, owing to the immune dysfunction in hospitalized patients. Such complications occurred more often in critically ill, hospitalized patients particularly those admitted in intensive care units and were reported as the major reason associated with a high mortality rate worldwide. Fungal pathogens most commonly associated with COVID-19 patients comprise members of the Mucorales (such as Rhizopus, Mucor, and Lichtheimia), as well as genera Aspergillus and Candida. In India, the prevalence rate of mucormycosis is relatively high than aspergillosis and candidiasis, and the predisposing risk factors associated with such infections included uncontrolled diabetes, underlying lung disease, leukopenia, neutropenia, malignancies and prolonged steroid therapy. However, co-infection with other fungi, including Alternariaand Scedosporium was also sporadically reported. These devastating invasive fungal infections are associated with differential mortality (high-low) and morbidity rates even after active management. The diagnosis of such infections is often challenging due to lack of sensitivity in contemporary diagnostic methods and poses an enormous challenge to healthcare experts. Thus, the role of early and accurate diagnosis, and management of such fungal infections, is vital in preventing life-threatening situations. Hence, this review focusses primarily on the epidemiology, predisposing risk factors, host environment, diagnosis and treatment of the most common medically important invasive fungal infections in immunocompromised conditions associated with COVID-19.

DNA logic gate for cancer cells identification, detection, and modulation of cell–cell interactions

The precise detection of cancer cells and modulation of cell–cell interactions would be highly desired for noninvasive and nontoxic cancer treatments but it remains challenging due to the existence of biomarkers on both normal and tumor cells. In this work, we engineered a logic-gated DNA molecular machine incorporating a membrane protein aptamer and an extracellular acid responsive split i-motif for the precise identification and detection of cancer cells, as well as the mediation of cell–cell interactions. In this system, only in the presence of both the membrane protein and protons, the logic-gated DNA molecular machine is activated to perform the “AND” logic operation to induce catalytic hairpin assembly (CHA) on the electrode, leading to the formation of G-quadruplex/hemin and the generation of an amplified electrochemical signal. On the other hand, the formed “AND” logic could hybridize with the DNA fragment on T-cell, effectively shorting the distance between T-cell and cancer cells. Benefiting from the DNA logic gate and CHA, this strategy could not only precisely identify cancer cells, but also show a sensitive analysis of cancer cells with a detection limit of 15 cells/mL. The logic-gated DNA molecular machine achieved the identification of cancer cells and modulation of intercellular interactions, providing a new idea for precise disease diagnosis and therapy.

Valence-engineered catalysis-selectivity regulation of molybdenum oxide nanozyme for acute kidney injury therapy and post-cure assessment.

The optimization of the enzyme-like catalytic selectivity of nanozymes for specific reactive oxygen species (ROS)-related applications is significant, and meanwhile the real-time monitoring of ROS is really crucial for tracking the therapeutic process. Herein, we present a mild oxidation valence-engineering strategy to modulate the valence states of Mo in Pluronic F127-coated MoO3-x nanozymes (denoted as MF-x, x: oxidation time) in a controlled manner aiming to improve their specificity of H2O2-associated catalytic reactions for specific therapy and monitoring of ROS-related diseases. Experimentally, MF-0 (Mo average valence 4.64) and MF-10 (Mo average valence 5.68) exhibit exclusively optimal catalase (CAT)- or peroxidase (POD)-like activity, respectively. Density functional theory (DFT) calculations verify the most favorable reaction path for both MF-0- and MF-10-catalyzed reaction processes based on free energy diagram and electronic structure analysis, disclosing the mechanism of the H2O2 activation pathway on the Mo-based nanozymes. Furthermore, MF-0 poses a strong potential in acute kidney injury (AKI) treatment, achieving excellent therapeutic outcomes in vitro and in vivo. Notably, the ROS-responsive photoacoustic imaging (PAI) signal of MF-0 during treatment guarantees real-time monitoring of the therapeutic effect and post-cure assessment in vivo, providing a highly desirable non-invasive diagnostic approach for ROS-related diseases.

Surge in Eye Drop Safety Concerns and Interest in Alternative Dry Eye Disease Therapy Following Eye Drop Recalls: A Cross-Sectional Google Trends Analysis.

Beginning in January 2023, numerous eye drops were recalled following reports of contamination. To investigate hesitancy in topical therapies for dry eye disease (DED), we analyzed trends in Internet search traffic for alternative DED therapies and eye drop safety concerns following initial recalls. Google Trends (GT) was used to measure the popularity of specific search terms during a given time period. The main GT output metric for gauging interest in a search term is the Search Volume Index (SVI). We collected worldwide SVI data for terms "dry eye vitamin," "are eye drops safe," "stop eye drops," "lipiflow," "ilux treatment," "dry eye mask," "dry eye warm compress," "omega-3 for dry eyes," "dry eye plugs," "dry eye humidifier," "itear," and "IPL dry eye" from April 24, 2022, to October 29, 2023. Statistical analysis was performed with Microsoft Excel v.16.77.1, and comparisons between groups were performed using paired t tests. A significant increase in SVI was observed for most keywords. When comparing the 40-week period before and after the initial recall, 7/10 alternative DED therapies demonstrated a statistically significant surge in Internet search traffic after recall (P < 0.05). Furthermore, 2/2 keywords pertaining to eye drop safety concerns demonstrated an increase in SVI (P < 0.0001). We identified a significant surge in Internet search activity for eye drop safety and alternative DED therapies following eye drop recalls. Public health agencies and physicians may find this information valuable while attempting to address safety concerns and navigating noncompliance of routine eye drop therapy.

Interpreting modern randomized controlled trials of medical therapy in inflammatory bowel disease.

Treatment options for the medical management of inflammatory bowel disease (IBD) have expanded substantially over the past decade. Multiple classes of advanced therapies, including both monoclonal antibodies and novel oral small molecules, are now available for the treatment of moderately-to-severely active Crohn's disease and ulcerative colitis, highlighted by the approvals of the first IL23p19 antagonists, selective Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. These advances have been accompanied by the identification of novel targets and the rapid growth in both the number and size of IBD clinical trials. Over a dozen landmark randomized controlled trials (RCTs) have been completed in the past 5 years, including the first head-to-head biologic trials, the first combination biologic studies, and multiple phase III registrational trials of novel compounds with new co-primary and composite end points that will change the treatment landscape for years to come. Importantly, the methodology of RCTs in IBD has evolved substantially, with new trial designs, evaluation of unique patient populations, and different types of efficacy and safety end points being key innovations. In this Review, we provide a comprehensive evaluation of how modern RCTs of IBD medical therapies have evolved and the implications for their appraisal that will help guide the application of these data to clinical practice.

Glucocorticoid chrono-pharmacology promotes glucose metabolism in heart through a cardiomyocyte-autonomous transactivation program.

Circadian time-of-intake gates the cardioprotective effects of glucocorticoid administration in both healthy and infarcted hearts. The cardiomyocyte-specific glucocorticoid receptor (GR) and its co-factor, Krüppel-like factor (Klf15), play critical roles in maintaining normal heart function in the long-term and serve as pleiotropic regulators of cardiac metabolism. Despite this understanding, the cardiomyocyte-autonomous metabolic targets influenced by the concerted epigenetic action of GR-Klf15 axis remain undefined. Here, we demonstrate the critical roles of the cardiomyocyte-specific GR and Klf15 in orchestrating a circadian-dependent glucose oxidation program within the heart. Combining integrated transcriptomics and epigenomics with cardiomyocyte-specific inducible ablation of GR or Klf15, we identified their synergistic role in the activation of adiponectin receptor expression (Adipor1) and the mitochondrial pyruvate complex (Mpc1/2), thereby enhancing insulin-stimulated glucose uptake and pyruvate oxidation. Furthermore, in obese diabetic (db/db) mice exhibiting insulin resistance and impaired glucose oxidation, light-phase prednisone administration, as opposed to dark-phase prednisone dosing, effectively restored cardiomyocyte glucose oxidation and improved diastolic function towards control-like levels in a sex-independent manner. Collectively, our findings uncover novel cardiomyocyte-autonomous metabolic targets of the GR-Klf15 axis. This study highlights the circadian-dependent cardioprotective effects of glucocorticoids on cardiomyocyte glucose metabolism, providing critical insights into chrono-pharmacological strategies for glucocorticoid therapy in cardiovascular disease.

Under-Prescription of Drugs in the Elderly Population of Western Romania: An Analysis Based on STOPP/START Version 2 Criteria

Background/Objectives: Numerous European countries, including Romania, are facing the concern of rapid ageing of their populations. Moreover, Romania’s life expectancy ranks among the lowest in the European Union. In light of this, it is imperative that the assessment of medication-related harm be given national priority in order to secure and enhance pharmacotherapy and the medical act. In this study, we sought to describe and evaluate the under-prescribing practices among the Romanian elderly population. Methods: We conducted a cross-sectional study in urban areas of two counties in Western Romania (Timis and Arad) from November 2017 to February 2019. We collected chronic electronic prescriptions issued for elderly patients (&gt;65 years old) with chronic conditions. The medication was prescribed by generalist or specialist physicians for periods ranging between 30 and 90 days. To assess inappropriate prescribing behaviours, a multidisciplinary team of specialists applied the Screening Tool of Older Persons’ Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) v.2 criteria to the collected prescriptions. Results: Within the 1498 prescriptions included in the study, 57% were issued to females, the mean age was 74.1 ± 6.95, and the average number of medicines per prescription was 4.7 ± 1.51. The STOPP criteria most commonly identified were the (1) long treatment duration (23.6%) and (2) prescription of neuroleptics (14.6%) or zopiclone (14.0%) as medications that increase the risk of falls. According to START criteria, the following medicines were under-prescribed: (1) statins (47.4%), (2) beta-blockers (24.5%), (3) antiresorptive therapy (10.0%), and (4) β2-agonists and muscarinic antagonists for chronic obstructive pulmonary disease (COPD) (4.5%). Within our study group, the prevalence of potentially inappropriate medications was 18.58%, whereas the prevalence of potential prescribing omissions was 49.2%. Conclusions: To decrease medication-related harm and morbid-mortality, and to increase the quality of life for elderly people in Romania, immediate actions are needed from national authorities. These actions include reinforcing primary care services, providing periodic training for physicians, implementing medication review services by pharmacists, and utilising electronic health records at their full capacity.

The Role of Gut Microbiota in the Efficacy and Side Effect Profile of Biologic Therapies for Autoimmune Diseases

The Role of Gut Microbiota in the Efficacy and Side Effect Profile of Biologic Therapies for Autoimmune Diseases

Current Capacity for Diagnosing Alzheimer's Disease in Germany and Implications for Wait Times.

Amyloid-targeting therapies for Alzheimer's disease (AD) might become available in Germany soon. The combination of a large pool of prevalent cases and a complex diagnostic process to determine eligibility for these treatments is likely to challenge health systems' capacity. To analyze Germany's healthcare system capacity to identify treatment-eligible patients in a timely and equitable manner. We modeled patients' diagnostic journey and projects wait times due to capacity constraints for AD specialist visits and PET scans from 2024 to 2043. Model parameters were derived from published data and expert input. Wait times would be ∼50 months over the model horizon, if patients were referred to specialists based on a brief cognitive assessment in primary care. Wait times for patients with social health insurance are projected to be 1.9 times those of patients with private insurance, with peak wait times of around 76 and 40 months, respectively. Adding a blood test for the AD pathology as additional triage step would reduce wait times to below 24 months. In spite of having a well-resourced health system, Germany is projected to be unable to cope with the demand for biomarker-based AD diagnosis, if a disease-modifying AD treatment were introduced. As these treatments might become available by the end of 2024, decisive action, in particular dissemination of high-performing AD blood tests for triage in primary care, will be needed to prevent delays in access and potentially avoidable and inequitable disease progression.

Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis.

The rise of induced pluripotent stem cells (iPSCs) technology has ushered in a landmark shift in the study of hereditary diseases. However, there is a scarcity of reports that offer a comprehensive and objective overview of the current state of research at the intersection of iPSCs and hereditary diseases. Therefore, this study endeavors to categorize and synthesize the publications in this field over the past decade through bibliometric methods and visual knowledge mapping, aiming to visually analyze their research focus and clinical trends. The English language literature on iPSCs and hereditary diseases, published from 2014 to 2023 in the Web of Science Core Collection (WoSCC), was examined. The CiteSpace (version 6.3.R1) software was utilized to visualize and analyze country/region, institution, scholar, co-cited authors, and co-cited journals. Additionally, the co-occurrence, clustering, and bursting of co-cited references were displayed. Analysis of 347 articles that met the inclusion criteria revealed a steady increase in the number of published articles and citation frequency in the field over the past decade. With regard to the countries/regions, institutions, scholars, and journals where the articles were published, the highest numbers were found in the USA, the University of California System, Suren M. Zakian, and Stem Cell Research, respectively. The current research is focused on the construction of disease models, both before and after correction, as well as drug target testing for single-gene hereditary diseases. Chromosome transplantation genomic therapy for hereditary diseases with abnormal chromosome structures may emerge as a future research hotspot in this field.

Increased CD14+HLA-DR-/low myeloid-derived suppressor cells can be regarded as a biomarker on disease severity and response to therapy in acute coronary syndrome

Purpose This study aimed to investigate the dynamic changes in monocytic myeloid-derived suppressor cells (M-MDSCs) and their implications in the pathogenesis of acute coronary syndrome (ACS), shedding light on potential therapeutic targets. Experimental Design Peripheral blood samples were collected from 68 ACS patients, 35 stable angina pectoris (SAP) patients, and 30 healthy controls (HC). Multi-parameter flow cytometry was employed for analysis of M-MDSCs, explored with disease characteristics and progression. Results ACS patients exhibited an increased frequency of circulating M-MDSCs compared to SAP patients and HC. M-MDSCs levels demonstrated associations with ACS type, coronary artery lesions, multi-vessel disease, and cardiac dysfunction severity. Higher M-MDSCs levels were found in obese patients. Notably, therapy led to a significant decrease in M-MDSCs frequency. Furthermore, ACS patients exhibited elevated levels of interleukin (IL)-6, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-α (TNF-α) in the cytokine profile associated with M-MDSCs. Increased expression of arginase-1(Arg-1) was observed in ACS patients, with positive correlations between M-MDSCs levels and IL-6, GM-CSF, and Arg-1 expression. The diagnostic performance of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and M-MDSCs levels varied in predicting the severity of coronary artery stenosis, with TG showing higher specificity, HDL-C displaying higher sensitivity, and M-MDSCs levels demonstrating balanced sensitivity and specificity. Conclusions Assessment of M-MDSCs frequency holds promise as a predictive marker for disease progression and therapy response of coronary artery stenosis. The elevated presence of M-MDSCs suggests their potential role in modulating ACS-related inflammation.

Supervised Exercise Therapy for Peripheral Artery Disease

This Teachable Moment discusses a woman in her 60s with hypertension, hyperlipidemia, coronary artery disease, and smoking history who presented with bilateral, aching leg pain triggered by walking and relieved by rest.

Management of COVID-19 patients of CT Severity 15/25 and above with Ayurveda drugs as add-on therapy – A Case Series

Ayurveda, which is the oldest life science in the world, has yet to be fully accepted as the only or even an additional therapy for severe diseases. It is a common perception that Ayurveda has a significant role in the preventive aspect of diseases, and the drugs of Ayurveda are more effective in chronic ailments. Most publications are also limited to these areas only, as use of Ayurveda in acute or severe cases is not yet justified scientifically because of the lack of significant scientific clinical data as very few case reports are published about the use of Ayurveda in acute cases. Here we present a case series of treatment of five COVID-19 patients with CT Severity 15/25 and above with Ayurveda drugs as add-on therapy admitted to tertiary care, a Level-3 COVID-19 treatment hospital. These five patients sought Ayurveda opinion and consented to Ayurveda treatment along with the ongoing treatment regime. All the patients showed improvement with Ayurveda treatment as an add-on therapy, and none of the patients needed ICU, and all patients were discharged when they started maintaining oxygen saturation at room air. This report addresses the clinical effectiveness of Ayurveda drugs as add-on therapy in severe cases of COVID -19. It also attempts to invite the attention of researchers towards the use of Ayurveda concepts and drugs in severe or acute cases of diseases.

Micro/Nanorobots for Advanced Light‐Based Biosensing and Imaging

AbstractSensing and imaging of biomolecules are crucial to disease diagnosis, prognosis, and therapy where optical techniques have essential utility. Untethered and remotely controlled micro/nanorobots have shown promising sensing and imaging capabilities, especially in complex biological environments. In this review, how micro/nanorobots are used for optical biosensing and imaging while highlighting the significant developments in the field is discussed. Starting is done by exploring colorimetric biosensing methods enabled by micro/nanorobots. Significant advancements in surface‐enhanced Raman spectroscopy‐integrated micro/nanorobots are reviewed. Further, state‐of‐the‐art optical bio‐imaging applications by micro/nanorobots at in vitro intracellular level are highlighted. Novel in vivo bio‐imaging assisted by optical micro/nanorobot sensors is examined. Furthermore, innovations in micro/nanorobots are assessed where motion augmentation is used as a detection mechanism, with applications in point‐of‐care molecular diagnostics. Finally, the challenges associated with micro/nanorobots‐assisted advanced optical biosensing and imaging while discussing insights about potential research directions for this rapidly progressing field are summarized.

7959 Combination Therapy Of Multi-Targeted Tyrosine Kinase Inhibitors And Immune Checkpoint Inhibitors In Advanced Adrenocortical Carcinoma

Abstract Disclosure: F. Yaylaci Mert: None. V. Balderrama Brondani: None. L.P. Marcal: None. M. Campbell: None. C. Jimenez: None. J. Varghese: None. A. Shah: None. M.A. Habra: None. Background: Adrenocortical carcinoma (ACC) is a rare cancer with limited response to systemic chemotherapies. Monotherapy with multi-targeted tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs) in ACC patients has limited efficacy. Combining TKIs with ICIs increased response rates in other malignancies but the efficacy of this approach in ACC is still unknown. This retrospective study aims to evaluate the efficacy and safety of the combined use of TKIs and ICIs in patients with advanced ACC. Methods: A single-center, retrospective cohort study in patients with advanced ACC treated with the combination of TKIs and ICIs. Response rates, progression-free survival (PFS), overall survival (OS) calculated from the time of combination, disease control rate (DCR), and safety profile were the main study objectives. Results: Seventeen patients were treated with combination therapy of TKI (lenvatinib or cabozantinib) and ICI (pembrolizumab) between January 2017 and December 2023. Eleven patients were women, the median age was 43.4 years (range 21.9-66.6), and 8 (47.1%) patients presented cortisol-producing tumors. All patients had prior systemic therapy, median of 3 (range 1-9) lines of therapy. The median duration of TKI+ICI therapy was 7.1 months (range 0.7-69.7). The treatment was discontinued in one patient due to a grade 3 adverse event (gastrointestinal fistula) after 1.6 months of treatment. Best overall responses were as follows: partial response 2 (13%), stable disease 8 (53%), and progressive disease 5 (34%). DCR was 58.8%. Median PFS was 7.1 months (range 0.7-66.4). One death occurred during the study due to disease progression. The median OS was 21.3 months (range 3.3-70.3). At the time of this report, 7 patients (41%) were still alive. Conclusion: The combined use of TKIs and ICIs in heavily treated ACC patients is associated with occasional durable responses and has a predictable and manageable side effect profile. This combination is worthy of a prospective clinical trial to validate the findings and establish new lines of therapy for this rare disease. Presentation: 6/2/2024

7824 Orbital Lymphoma masquerading as Thyroid Eye Disease

Abstract Disclosure: S. Ganawa: None. S. Joseph: None. C. Anshuman: None. D. Luciane L: None. A. Sajid: None. C. Anne: None. S. Dhage: None. Thyroid eye disease (TED) is the most common extrathyroidal manifestation in Graves’ disease (GD). In this case report, we present a case of a 64 years old lady, who was initially diagnosed with thyroid eye disease about 9 years ago. However, she was clinically and biochemically euthyroid. She was offered an orbital decompression surgery by local ophthalmology team. Patient wasn’t keen on the surgery at this stage.Recently she experienced increased swelling of her eyes, with conjunctival redness, oedema, and diplopia bilaterally, more evident on the left side. She was initiated on intravenous methylprednisolone (IVMP) weekly, by local ophthalmology team and was referred to our specialist thyroid eye clinic for further management.On presentation to us, her clinical activity score (CAS) was 5/7, but she was euthyroid clinically and biochemically. She was continued on weekly IVMP and oral mycophenolate mofetil (MMF) was added on as per the latest EUGOGO guidelines published in 2021. Her treatment was reviewed after the anti thyroperoxidase (TPO) and anti-Thyroid Stimulating Hormone receptor (TSH) antibodies were reported as negative and her eyes worsened despite the treatment with IVMP and MMF.Her repeat MR orbit at this stage showed possible orbital lymphoma. Her immunosuppressive medications were discontinued at this stage. After further discussions at regional thyroid eye MDT and radiology MDT, an orbital biopsy was arranged for, which confirmed Extra nodal Marginal Zone lymphoma, with no high-grade component. She has been referred to the oncology unit for further assessment and management.This case highlights the importance of considering alternative differential diagnosis in certain patients with atypical features or those who are non-responders to the first line immunosuppressive therapies for thyroid eye disease. Details of this case and relevant literature will be reviewed in this report. Presentation: 6/3/2024