Clinical Viability Research Articles

Automatic Landmark Detection for Preoperative Planning of High Tibial Osteotomy Using Traditional Feature Extraction and Deep Learning Methods.

Automatic High Tibial Osteotomy (HTO) landmark detection methods promise to improve the effectiveness and standardisation of HTO preoperative planning. Unfortunately, due to the limited number of HTO datasets, existing methods are less robust when dealing with patients with varied deformities than traditional manual planning, severely limiting their clinical viability and application in practical surgical settings. Here, we present a new HTO landmark detection framework using an integration of optimised heatmap-offset aggregation method and traditional feature extraction. Subjective and objective approaches were employed to reflect the final clinical acceptance of our model. Average Mean Absolute Error of prediction results compared to the surgeon's gold standard was 0.35° for the hip-knee-ankle angle. The objective score rated by surgeons reached 4.4 on a scale of 5. The study demonstrated that the automatic detection method has great potential serving as an alternative to manual radiological analysis in practical surgical pre-operative planning.

A leadless power transfer and wireless telemetry solutions for an endovascular electrocorticography.

Endovascular brain-computer interfaces (eBCIs) offer a minimally invasive way to connect the brain to external devices, merging neuroscience, engineering, and medical technology. Currently, solutions for endovascular electrocorticography (ECoG) include a stent in the brain with sensing electrodes, a chest implant to accommodate electronic components to provide power and data telemetry, and a long (tens of centimeters) cable travel through vessels with a set of wires in between. Removing this long cable is the key to the clinical viability of eBCIS as it carries risks and limitations, especially for patients with fragile vasculature. This work introduces a wireless and leadless telemetry and power transfer solution for ECoG. The proposed solution includes an optical telemetry module and a focused ultrasound (FUS) power transfer system. The proposed system can be miniaturised to fit in an endovascular stent, removing the need for long, intrusive cables. The optical telemetry achieves data transmission speeds of over 2 Mbit/s, capable of supporting 41 ECoG channels at a 2 kHz sampling rate with 24-bit resolution. The FUS power transfer system delivers up to 10 mW of power to the implant through the scalp(6mm), skull(10mm), and subdural space(5mm), adhering to safety limits. Testing on bovine tissue (10 mm thick bone, 7 mm thick skin) confirmed the system's efficacy. This leadless and wireless solution eliminates the need for long cables and auxiliary implants, potentially reducing complications and enhancing the clinical applicability of eBCIs. The proposed system represents a step forward in enabling safer and more effective ECoG for a broader range of patients.

Clinical target volume (CTV) automatic delineation using deep learning network for cervical cancer radiotherapy: A study with external validation.

To explore the accuracy and feasibility of a proposed deep learning (DL) algorithm for clinical target volume (CTV) delineation in cervical cancer radiotherapy and evaluate whether it can perform well in external cervical cancer and endometrial cancer cases for generalization validation. A total of 332 patients were enrolled in this study. A state-of-the-art network called ResCANet, which added the cascademulti-scale convolution in the skip connections to eliminate semantic differences between different feature layers based on ResNet-UNet. The atrous spatial pyramid pooling in the deepest feature layer combined the semantic information of different receptive fields without losing information. A total of 236 cervical cancer cases were randomly grouped into 5-fold cross-training (n=189) and validation (n=47) cohorts. External validations were performed ina separate cohort of 54 cervical cancer and 42 endometrial cancer cases. The performances of the proposed network were evaluated by dice similarity coefficient (DSC), sensitivity (SEN), positive predictive value (PPV), 95% Hausdorff distance (95HD), and oncologist clinical score when comparing them with manual delineation in validation cohorts. In internal validation cohorts, the mean DSC, SEN, PPV, 95HD for ResCANet achieved 74.8%, 81.5%, 73.5%, and 10.5mm. In external independent validation cohorts, ResCANet achieved 73.4%, 72.9%, 75.3%, 12.5mm for cervical cancer cases and 77.1%, 81.1%, 75.5%, 10.3mm for endometrial cancer cases, respectively. The clinical assessment score showed that minor and no revisions (delineation time was shortened to within 30min) accountedforabout 85% of all cases in DL-aided automatic delineation. We demonstrated the problem of model generalizability for DL-based automatic delineation. The proposed network can improve the performance of automatic delineation for cervical cancer and shorten manual delineation time at no expense to quality. The network showed excellent clinical viability, which can also be even generalized for endometrial cancer with excellent performance.

Non-invasive brain-machine interface control with artificial intelligence copilots.

Motor brain-machine interfaces (BMIs) decode neural signals to help people with paralysis move and communicate. Even with important advances in the last two decades, BMIs face key obstacles to clinical viability. Invasive BMIs achieve proficient cursor and robotic arm control but require neurosurgery, posing significant risk to patients. Non-invasive BMIs do not have neurosurgical risk, but achieve lower performance, sometimes being prohibitively frustrating to use and preventing widespread adoption. We take a step toward breaking this performance-risk tradeoff by building performant non-invasive BMIs. The critical limitation that bounds decoder performance in non-invasive BMIs is their poor neural signal-to-noise ratio. To overcome this, we contribute (1) a novel EEG decoding approach and (2) artificial intelligence (AI) copilots that infer task goals and aid action completion. We demonstrate that with this "AI-BMI," in tandem with a new adaptive decoding approach using a convolutional neural network (CNN) and ReFIT-like Kalman filter (KF), healthy users and a paralyzed participant can autonomously and proficiently control computer cursors and robotic arms. Using an AI copilot improves goal acquisition speed by up to 4.3 × in the standard center-out 8 cursor control task and enables users to control a robotic arm to perform the sequential pick-and-place task, moving 4 randomly placed blocks to 4 randomly chosen locations. As AI copilots improve, this approach may result in clinically viable non-invasive AI-BMIs.

Oncolytic activity of a coxsackievirus B3 strain in patient-derived cervical squamous cell carcinoma organoids and synergistic effect with paclitaxel

BackgroundCervical squamous cell carcinoma (CSCC) is a prevalent gynecological malignancy worldwide. Current treatments for CSCC can impact fertility and cause long-term complications, underscoring the need for new therapeutic strategies. Oncolytic virotherapy has emerged as a promising option for cancer treatment. Previous research has demonstrated the oncolytic activity of the coxsackievirus B3 strain 2035 A (CVB3/2035A) against various tumor types. This study aims to evaluate the clinical viability of CVB3/2035A for CSCC treatment, focusing on its oncolytic effect in patient-derived CSCC organoids.MethodsThe oncolytic effects of CVB3/2035A were investigated using human CSCC cell lines in vitro and mouse xenograft models in vivo. Preliminary tests for tumor-selectivity were conducted on patient-derived CSCC tissue samples and compared to normal cervical tissues ex vivo. Three patient-derived CSCC organoid lines were developed and treated with CVB3/2035A alone and in combination with paclitaxel. Both cytotoxicity and virus replication were evaluated in vitro.ResultsCVB3/2035A exhibited significant cytotoxic effects in human CSCC cell lines and xenograft mouse models. The virus selectively induced oncolysis in patient-derived CSCC tissue samples while sparing normal cervical tissues ex vivo. In patient-derived CSCC organoids, which retained the immunohistological characteristics of the original tumors, CVB3/2035A also demonstrated significant cytotoxic effects and efficient replication, as evidenced by increased viral titers and presence of viral nucleic acids and proteins. Notably, the combination of CVB3/2035A and paclitaxel resulted in enhanced cytotoxicity and viral replication.ConclusionsCVB3/2035A showed oncolytic activity in CSCC cell lines, xenografts, and patient-derived tissue cultures and organoids. Furthermore, the virus exhibited synergistic anti-tumor effects with paclitaxel against CSCC. These results suggest CVB3/2035A could serve as an alternative or adjunct to current CSCC chemotherapy regimens.

Deep learning-based segmentation for high-dose-rate brachytherapy in cervical cancer using 3D Prompt-ResUNet

Objective.To develop and evaluate a 3D Prompt-ResUNet module that utilized the prompt-based model combined with 3D nnUNet for rapid and consistent autosegmentation of high-risk clinical target volume (HRCTV) and organ at risk (OAR) in high-dose-rate brachytherapy for cervical cancer patients.Approach.We used 73 computed tomography scans and 62 magnetic resonance imaging scans from 135 (103 for training, 16 for validation, and 16 for testing) cervical cancer patients across two hospitals for HRCTV and OAR segmentation. A novel comparison of the deep learning neural networks 3D Prompt-ResUNet, nnUNet, and segment anything model-Med3D was applied for the segmentation. Evaluation was conducted in two parts: geometric and clinical assessments. Quantitative metrics included the Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95%), Jaccard index (JI), and Matthews correlation coefficient (MCC). Clinical evaluation involved interobserver comparison, 4-grade expert scoring, and a double-blinded Turing test.Main results.The Prompt-ResUNet model performed most similarly to experienced radiation oncologists, outperforming less experienced ones. During testing, the DSC, HD95% (mm), JI, and MCC value (mean ± SD) for HRCTV were 0.92 ± 0.03, 2.91 ± 0.69, 0.85 ± 0.04, and 0.92 ± 0.02, respectively. For the bladder, these values were 0.93 ± 0.05, 3.07 ± 1.05, 0.87 ± 0.08, and 0.93 ± 0.05, respectively. For the rectum, they were 0.87 ± 0.03, 3.54 ± 1.46, 0.78 ± 0.05, and 0.87 ± 0.03, respectively. For the sigmoid, they were 0.76 ± 0.11, 7.54 ± 5.54, 0.63 ± 0.14, and 0.78 ± 0.09, respectively. The Prompt-ResUNet achieved a clinical viability score of at least 2 in all evaluation cases (100%) for both HRCTV and bladder and exceeded the 30% positive rate benchmark for all evaluated structures in the Turing test.Significance.The Prompt-ResUNet architecture demonstrated high consistency with ground truth in autosegmentation of HRCTV and OARs, reducing interobserver variability and shortening treatment times.

Data-driven determination of 1H-MRS basis set composition.

Metabolite amplitude estimates derived from linear combination modeling of MR spectra depend upon the precise list of constituent metabolite basis functions used (the "basis set"). The absence of clear consensus on the "ideal" composition or objective criteria to determine the suitability of a particular basis set contributes to the poor reproducibility of MRS. In this proof-of-concept study, we demonstrate a novel, data-driven approach for deciding the basis-set composition using Bayesian information criteria (BIC). We have developed an algorithm that iteratively adds metabolites to the basis set using iterative modeling, informed by BIC scores. We investigated two quantitative "stopping conditions", referred to as max-BIC and zero-amplitude, and whether to optimize the selection of basis set on a per-spectrum basis or at the group level. The algorithm was tested using two groups of synthetic in-vivo-like spectra representing healthy brain and tumor spectra, respectively, and the derived basis sets (and metabolite amplitude estimates) were compared to the ground truth. All derived basis sets correctly identified high-concentration metabolites and provided reasonable fits of the spectra. At the single-spectrum level, the two stopping conditions derived the underlying basis set with 77-87% accuracy. When optimizing across a group, basis set determination accuracy improved to 84-92%. Data-driven determination of the basis set composition is feasible. With refinement, this approach could provide a valuable data-driven way to derive or refine basis sets, reducing the operator bias of MRS analyses, enhancing the objectivity of quantitative analyses, and increasing the clinical viability of MRS.

Complement-targeted therapeutics: Are we there yet, or just getting started?

Therapeutic interventions in the complement system, a key immune-inflammatory mediator and contributor to a broad range of clinical conditions, have long been considered important yet challenging or even unfeasible to achieve. Almost 20 years ago, a spark was lit demonstrating the clinical and commercial viability of complement-targeted therapies. Since then, the field has experienced an impressive expansion of targeted indications and available treatment modalities. Currently, a dozen distinct complement-specific therapeutics covering several intervention points are available in the clinic, benefiting patients suffering from eight disorders, not counting numerous clinical trials and off-label uses. Observing this rapid rise of complement-targeted therapy from obscurity to mainstream with amazement, one might ask whether the peak of this development has now been reached or whether the field will continue marching on to new heights. This review looks at the milestones of complement drug discovery and development achieved so far, surveys the currently approved drug entities and indications, and ventures a glimpse into the future advancements yet to come.

Computational Modeling Approach to Profile Hemodynamical Behavior in a Healthy Aorta.

Cardiovascular diseases (CVD) remain the leading cause of mortality among older adults. Early detection is critical as the prognosis for advanced-stage CVD is often poor. Consequently, non-invasive diagnostic tools that can assess hemodynamic function, particularly of the aorta, are essential. Computational fluid dynamics (CFD) has emerged as a promising method for simulating cardiovascular dynamics efficiently and cost-effectively, using increasingly accessible computational resources. This study developed a CFD model to assess the aorta geometry using tetrahedral and polyhedral meshes. A healthy aorta was modeled with mesh sizes ranging from 0.2 to 1 mm. Key hemodynamic parameters, including blood pressure waveform, pressure difference, wall shear stress (WSS), and associated wall parameters like relative residence time (RRT), oscillatory shear index (OSI), and endothelial cell activation potential (ECAP) were evaluated. The performance of the CFD simulations, focusing on accuracy and processing time, was assessed to determine clinical viability. The CFD model demonstrated clinically acceptable results, achieving over 95% accuracy while reducing simulation time by up to 54%. The entire simulation process, from image construction to the post-processing of results, was completed in under 120 min. Both mesh types (tetrahedral and polyhedral) provided reliable outputs for hemodynamic analysis. This study provides a novel demonstration of the impact of mesh type in obtaining accurate hemodynamic data, quickly and efficiently, using CFD simulations for non-invasive aortic assessments. The method is particularly beneficial for routine check-ups, offering improved diagnostics for populations with limited healthcare access or higher cardiovascular disease risk.

Innovations in Bioink Materials and 3D Bioprinting for Precision Tissue Engineering

The progress in bioink materials and 3D bioprinting techniques has created new opportunities in tissue engineering. The goal is to develop cellular implants that closely resemble native tissues in structure, function, and microenvironment, addressing challenges such as nutrient transport and mechanical support for tissue regeneration. This literature review evaluates current trends in bioink development and 3D bioprinting methodologies, assessing their effectiveness for enhancing tissue-engineered constructs for clinical applications. Recent studies were comprehensively analyzed, focusing on novel bioink formulations, optimization of 3D bioprinting processes, and evaluate on of printed constructs' mechanical and biological properties. Various fabrication techniques and their implications for tissue integration were examined. The review shows significant progress in bioink compositions that enhance cell viability and nutrient diffusion within printed scaffolds. Constructs demonstrated improved mechanical properties and biological functionality, enabling better integration with host tissues. In vivo studies highlighted the potential of these bioprinted tissues to support cellular activity and regeneration, signifying significant advancements in clinical viability. The findings emphasize the crucial role of bioink materials and bioprinting technology in advancing tissue engineering. Continual innovation in bioink formulation and printing techniques is essential to overcome current limitations and achieve widespread clinical application. Future research should focus on personalized bioink development and expanding the range of tissues that can be effectively engineered, ultimately improving patient outcomes in regenerative medicine.

Integration of hyperthermic intraperitoneal chemotherapy with cytoreductive surgery for ovarian cancer in Iraq: Navigating challenges in a resource-limited setting

In Iraq, the application of hyperthermic intraperitoneal chemotherapy combined with cytoreductive surgery is a novel therapeutic strategy for ovarian cancer with peritoneal carcinomatosis. This study at the Arby Private Hospital represents the pioneering use of this modality in a resource-limited setting. It evaluates procedural effectiveness, elucidates the systemic challenges within the healthcare framework, and identifies the imperatives for medical training enhancement. The findings illuminate the clinical viability and outline necessary strategies for broader integration of advanced therapies into the Iraqi health-care paradigm, emphasizing a pressing need for policy and infrastructural reforms to elevate oncologic care.

Clinical and biochemical responses to treatment of uncomplicated severe acute malnutrition: a multicenter observational cohort from the OptiDiag study

BackgroundSevere acute malnutrition (SAM) can be diagnosed using weight-for-height Z-score (WHZ) and/or mid-upper arm circumference (MUAC). Although some favor using MUAC alone, valuing its presumed ability to identify children at greatest need for nutritional care, the functional severity and physiological responses to treatment in children with varying deficits in WHZ and MUAC remain inadequately characterized. ObjectiveWe aimed to compare clinical and biochemical responses to treatment in children with 1) both low MUAC and low WHZ, 2) low MUAC-only, and 3) low WHZ-only. MethodsA multicenter, observational cohort study was conducted in children aged 6–59 mo with nonedematous, uncomplicated SAM in Bangladesh, Burkina Faso, and Liberia. Anthropometric measurements and critical indicators were collected 3 times during treatment; metrics included clinical status, nutritional status, viability, and serum leptin, a biomarker of mortality risk in SAM. ResultsChildren with combined MUAC and WHZ deficits had greater increases in leptin levels during treatment than those with low MUAC alone, showing a 34.4% greater increase on the second visit (95% confidence interval [CI]: 7.6%, 43.6%; P = 0.02) and a 34.3% greater increase on the third visit (95% CI: 13.2%, 50.3%; P = 0.01). Similarly, weight gain velocity was higher by 1.56 g/kg/d in the combined deficit group (95% CI: 0.38, 2.75; P = 0.03) compared with children with low MUAC-only. Children with combined deficits had higher rates of iron deficiency and wasting while those with low WHZ alone and combined deficits had higher rates of tachypnea and pneumonia during treatment. ConclusionsGiven the comparable treatment responses of children with low WHZ alone and those with low MUAC alone, and the greater vulnerability at admission and during treatment in those with combined deficits, our findings support retaining WHZ as an independent diagnostic and admission criterion of SAM, alongside MUAC.This trial was registered at www.clinicaltrials.gov/study/NCT03400930 as NCT03400930.

Delivery vehicle and route of administration influences self-amplifying RNA biodistribution, expression kinetics, and reactogenicity

Self-amplifying RNA (saRNA) is a next-generation RNA platform derived from an alphavirus that enables replication in host cytosol, offering a promising shift from traditional messenger RNA (mRNA) therapies by enabling sustained protein production from minimal dosages. The approval of saRNA-based vaccines, such as the ARCT-154 for COVID-19 in Japan, underscores its potential for diverse therapeutic applications, including vaccine development, cancer immunotherapy, and gene therapy. This study investigates the role of delivery vehicle and administration route on saRNA expression kinetics and reactogenicity. Employing ionizable lipid-based nanoparticles (LNPs) and polymeric nanoparticles, we administered saRNA encoding firefly luciferase to BALB/c mice through six routes (intramuscular (IM), intradermal (ID), intraperitoneal (IP), intranasal (IN), intravenous (IV), and subcutaneous (SC)), and observed persistent saRNA expression over a month. Our findings reveal that while LNPs enable broad route applicability and stability, pABOL (poly (cystamine bisacrylamide-co-4-amino-1-butanol)) formulations significantly amplify protein expression via intramuscular delivery. Notably, the disparity between RNA biodistribution and protein expression highlight the nuanced interplay between administration routes, delivery vehicles, and therapeutic outcomes. Additionally, our research unveiled distinct biodistribution profiles and inflammatory responses contingent upon the chosen delivery formulation and route. This research illuminates the intricate dynamics governing saRNA delivery, biodistribution and reactogenicity, offering essential insights for optimizing therapeutic strategies and advancing the clinical and commercial viability of saRNA technologies.

Synergistic Gold Nanorod‐based Chemo‐Photothermal Therapy: A Promising Nanoparticle Approach for Refractory Multidrug‐Resistant Cancer

AbstractMultidrug resistance (MDR) remains a formidable challenge in cancer treatment, necessitating innovative strategies to enhance therapeutic outcomes. This review explores the potential of a synergistic gold nanorod (GNR) therapy (SGNRT) utilizing GNRs as multifunctional platforms for co‐delivering chemotherapy and thermal therapies. The rational design of SGNRT systems enables targeted payload delivery, circumvention of Adenosine triphosphate (ATP)‐binding cassette drug efflux transporters, and hyperthermia‐induced chemo sensitization. In vitro studies demonstrate the synergistic impact of SGNRT in overcoming MDR, emphasizing its potential for enhanced antitumor efficacy. However, further in vivo investigations are essential to assess the clinical viability of this nanoparticle (NP)‐directed approach against advanced multidrug‐resistant malignancies. The integration of SGNRT holds promise for advancing precision cancer therapies and addressing the intricate challenges of drug resistance in clinical settings.

Tractography from T1-weighted MRI: empirically exploring the clinical viability of streamline propagation without diffusion MRI

Abstract Over the last few decades, diffusion MRI (dMRI) streamline tractography has emerged as the dominant method for in vivo estimation of white matter (WM) pathways in the brain. One key limitation to this technique is that modern tractography implementations require high angular resolution diffusion imaging (HARDI). However, HARDI can be difficult to collect clinically, limiting the reach of tractography analyses to research cohorts and thus limiting many WM investigations to certain populations and pathologies. As such, a clinically viable tractography solution applicable to wider patient populations scanned as a part of routine care would be of key significance in broadening WM analyses to underfunded or rarer diseases and to the clinical setting. Such a solution would require the ability to perform arbitrary tractography analyses, use only clinical imaging for input, and be open source and widely accessible and implementable. Thus, here we evaluate our recently developed, containerized and open-source, T1-weighted (T1w) MRI-based deep learning model for streamline propagation. We empirically assess its performance against traditional dMRI-based and established atlas-based approaches in a healthy young population, an aging one, and in those with epilepsy, depression, and brain cancer. In the healthy young population, we find slightly increased error compared to traditional tractography with the deep learning model that falls within the bounds attributable to dMRI variability and is considerably less than the atlas-based approach. Further, seeking to replicate previously published dMRI tractography effects in the remaining cohorts as an initial assessment of clinical viability, we find this model successfully does so in some key cases—particularly in applications that rely on long-range streamlines including those not captured by the atlas-based approach—but importantly not all. These results suggest a deep learning-based approach to tractography with T1w MRI demonstrates promise within the limitations of our definition of clinical viability and especially over atlas-based approaches but requires refinement and more robust consideration of out-of-distribution effects prior to widespread clinical use. We also find these results raise additional questions regarding the differences in image content between dMRI and T1w MRI and their relationship to tractography. Further investigation of these questions will improve the field’s understanding of which features of the brain influence measured tractography effects.

Intelligent ankle–foot prosthesis based on human structure and motion bionics

The ankle–foot prosthesis aims to compensate for the missing motor functions by fitting the motion characteristics of the human ankle, which contributes to enabling the lower-limb amputees to take care of themselves and improve mobility in daily life. To address the problems of poor bionic motion of the ankle–foot prosthesis and the lack of natural interaction among the patient, prosthesis, and the environment, we developed a complex reverse-rolling conjugate joint based on the human ankle–foot structure and motion characteristics, the rolling joint was used to simulate the rolling-sliding characteristics of the knee joint. Meanwhile, we established a segmental dynamics model of the prosthesis in the stance phase, and the prosthetic structure parameters were obtained with the optimal prosthetic structure dimensions and driving force. In addition, a carbon fiber energy-storage foot was designed based on the human foot profile, and the dynamic response of its elastic strain energy at different thicknesses was simulated and analyzed. Finally, we integrated a bionic ankle–foot prosthesis and experiments were conducted to verify the bionic nature of the prosthetic joint motion and the energy-storage characteristics of the carbon fiber prosthetic foot. The proposed ankle–foot prosthesis provides ambulation support to assist amputees in returning to social life normally and has the potential to help improve clinical viability to reduce medical rehabilitation costs.

Hypericum perforatum-derived exosomes-like nanovesicles for adipose tissue photodynamic therapy

BackgroundRecent investigations underscore the capacity of photodynamic therapy (PDT) to induce adipocyte apoptosis, thereby mitigating obesity. Nonetheless, extant synthetic photosensitizers manifest limitations that hinder their clinical viability. PurposeIn the current study, we used Hypericum perforatum-derived exosomes-like nanovesicles (HPExos) as a novel photosensitizer, and investigated its PDT effects in adipose tissue during obesity. MethodHPExos-were administered to high fat diet mice via intraperitoneal injection, followed by targeted irradiation with specialized LED lights. Mass spectrometric analysis was analyzed in adipose tissues. CCK8 assay and Oil Red O staining were used to investigate lipid accumulation in 3T3-L1 cells to clarify adipocyte differentiation. The expression levels of related markers associated with adipogenesis and lipogenesis were assessed by RT-PCR. Apoptosis analysis was performed by TUNEL staining of and western blotting. ResultsHPExos combined with PDT accumulated in visceral white adipose tissues results in a reduced body weight and improved insulin sensitivity. HPExos combined with PDT induced apoptosis by driving high levels of ROS. In addition, HPExos combined with PDT significantly downregulated the expression of transcription factors, PPARγ, C/EBPα, and SREBP and lipogenesis protein FABP4 both in vitro and in vivo, associated with a decreased FFA levels. ConclusionThese findings suggest that HPExos could act as an effective photosensitizer in regulating glucose hemostasis by inhibiting adipocyte differentiation and lipogenesis, offering a promising approach for obesity treatment.

P-262 Clinical viability of oocytes with micronuclei at fertilisation

Abstract Study question Does the presence of micronuclei at fertilisation impact on embryo potential? Summary answer Embryos displaying micronuclei at fertilisation exhibit decreased utilisation rates and lower euploidy rates, however are capable of resulting in clinical pregnancies. What is known already The appearance of two pronuclei defines normal fertilisation. With advances in imaging techniques, a range of pronuclei phenotypes can now be identified in more detail, including additional micronuclei. Micronuclei are smaller satellite structures appearing around the pronuclei. Previous studies have determined that embryos containing two primary pronuclei and one micronuclei are generally diploid and can develop to blastocyst stage. However, these studies were limited in sample size, did not have consistent imaging techniques and assessed only the presence or absence of micronuclei, not their size or number. Study design, size, duration Retrospective cohort analysis in a single, large IVF centre including all oocytes entering culture between January 2022 and December 2023 (n = 33,237). All embryos were cultured in Embryoscope+ using Vitrolife sequential media at 6% CO2 and 5% O2. ICSI and naturally inseminated oocytes were included. All embryos were cultured to day 5/6 before determining suitability for transfer, freezing and/or genetic testing. Participants/materials, setting, methods During routine daily annotation, embryologists assessed fertilised oocytes for the presence of micronuclei. This study re-examined all embryos annotated as displaying micronuclei and further assessed: number of micronuclei, their position (‘apposed’ or ‘distant’ from the pronuclei, and in the case of > 1 micronuclei ‘clustered’ or ‘spread’) along with the area (μm2) of the two largest micronuclei and area (μm2) of primary pronuclei using Embryoscope+ software. Clinical pregnancy was defined as presence of a gestational sac. Main results and the role of chance Micronuclei were observed in 0.45% (n = 149/33,237) of all oocytes assessed. The majority of these presented as one additional nuclei 92.60% (n = 138), 7.38% (n = 11) showed two additional nuclei and 0.67%(n = 1) had multiple (more than 2) micronuclei. All micronuclei appeared apposing a primary pronucleus. In the event of multiple micronuclei, 82% were clustered whereas 9% was spread throughout the around the primary pronuclei. The average area of the largest micronuclei in each oocyte was 80.33μm2 ± 26.81.The mean area of all micronuclei was 76.80μm2, approximately 16% of the size of primary pronuclei measured, 465.09μm2. The utilisation rates of embryos derived from micronuclei fertilisation were 28.18% (N = 42) compared to 49%, n = 4118 of 2PN derived embryos. All but one of these presented two primary pronuclei and one additional micronuclei, with the remaining embryo displaying two micronuclei. Twelve of these embryos were transferred (in a fresh stimulated cycle (n = 5) or a subsequent frozen embryo transfer cycle (n = 7), resulting in four clinical pregnancies, however only one ongoing clinical pregnancy. PGT testing was performed on 19 embryos, with only two, 6.67% returning a euploid results, 68.42% resulting an aneuploid, of the remaining four embryos, 2 achieved a mosaic result and 2 received a no result. Limitations, reasons for caution As the occurrence of micronuclei is rare, only a limited number of embryos were available for analysis. Furthermore, this study was conducted in a large single laboratory and can not account for differences in culture conditions between laboratories. Inter-operator variability among initial fertilisation annotations could not be excluded. Wider implications of the findings By creating a definition of the micronuclei measurement, it provides safeguard for micronuclei to be assessed in culture. The data presented here can help guide clinical decisions where micronuclei are present. Trial registration number not applicable

Approach to Renovascular Hypertension

ABSTRACT The article describes the case of a 68-year-old man with poorly controlled hypertension, diabetes, and coronary artery disease, highlighting potential underlying causes of his condition, particularly secondary hypertension due to renal artery stenosis. His clinical evaluation reveals risk factors such as prolonged smoking, obesity, and peripheral vascular disease. Clinical examinations indicate significant blood pressure discrepancies between limbs and the presence of renal bruits, leading to the suspicion of renovascular hypertension. Resistant hypertension can often stem from renal causes, specifically atherosclerotic renal artery disease. Diagnostic approaches are detailed, including various imaging techniques and criteria for assessing renal artery stenosis. Management options are discussed, exploring both medical and interventional therapies. Although recent trials like ASTRAL, CORAL, and STAR showed limited benefits of revascularisation over medical management, selected patients may still benefit from intervention. The case underscores the importance of individualised patient evaluation for managing secondary hypertension and renovascular disease, considering both clinical presentation and renal parenchymal viability.

Evaluation of nanocellulose-based anthraquinone from marine fungi Penicillium flavidorsum as an alternative therapy for skin wound healing: histopathological and immunohistochemical evidences from a rat model

BackgroundWound healing represents a complex clinical challenge, necessitating the selection of appropriate wound dressings to facilitate an efficient healing process. This study aims to explore an effective approach to enhance wound healing by investigating the therapeutic potential of a nanocellulose-based anthraquinone derived from marine fungi.Forty male Wistar rats were divided into five groups, including a control group and various four treatment groups. The wound healing process was assessed by measuring the wound area at different time points.ResultsThe results showed promising outcomes in terms of wound healing progression. The group treated with anthraquinone and nanocellulose demonstrated the most favorable results, with normal epidermal architecture, marked hyperkeratosis, and minimal dermal edema. This study provides comprehensive evidence supporting the efficacy of this novel alternative therapy through histopathological and immunohistochemical analyses conducted on a rat model.ConclusionBy addressing the limitations associated with conventional wound dressings, our research contributes to the development of innovative strategies for optimizing wound healing outcomes. The findings presented herein underscore the potential of nanocellulose-based anthraquinone as a promising therapeutic option for promoting skin wound healing. Further investigations are warranted to elucidate the underlying mechanisms and establish the clinical viability of this alternative therapy.