In silico trials of acute ischemic stroke: predicting the total potential for improvement to patient functional outcomes

Claire M. Miller; Raymond Padmos; Praneeta Konduri; Tamás István Józsa; Yidan Xue; Nerea Arrarte Terreros; Max van der Kolk; Stephen Payne; Henk Marquering; Charles Majoie Alfons Hoekstra

arXiv · 2511.02088

In silico trials of acute ischemic stroke: predicting the total potential for improvement to patient functional outcomes

Claire M. Miller·Raymond Padmos·Praneeta Konduri·Tamás István Józsa·Yidan Xue·Nerea Arrarte Terreros·Max van der Kolk·Stephen Payne·Henk Marquering·Charles Majoie Alfons Hoekstra

View original source ↗Read source document ↗Export metadata ↓

Abstract

This study uses in silico trials (ISTs) to quantify the potential for benefit due to improved recanalisation outcomes and shorter time to treatment for acute ischaemic stroke (AIS) patients. We use an IST framework to run trials on cohorts of virtual patients with early and late treatment after stroke onset, and with successful (full) and unsuccessful (no) recanalisation outcomes. Using a virtual population of AIS patients, and in silico models of blood flow, perfusion, and tissue death, we predict the functional independence of each patient at 90 days using the modified Rankin Scale (mRS). Results predict 57% of the virtual population achieve functional independence with full recanalisation and a treatment time of 4 hours or less, compared to 29% with no recanalisation and more than 4 hours to treatment. Successful recanalisation was more beneficial than faster treatment: the best-case common odds ratio (improved mRS) due to recanalisation was 2.7 compared to 1.6 for early treatment. This study provides a proof-of-concept for a novel use-case of ISTs: quantifying the maximum potential for improvement to patient outcomes. This would be useful during early stages of therapy development, to determine the target populations and therapy goal with the greatest potential for population improvements.

Explore related subjects

q-bio.TO

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

Claire M. Miller, Raymond Padmos, Praneeta Konduri, Tamás István Józsa, Yidan Xue, Nerea Arrarte Terreros, Max van der Kolk, Stephen Payne, Henk Marquering, Charles Majoie Alfons Hoekstra. 2025-11-03. In silico trials of acute ischemic stroke: predicting the total potential for improvement to patient functional outcomes. https://arxiv.org/abs/2511.02088

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

arXiv2026

Simulation and Analysis of Solute Transport in Multi-Lymphangion Lymphatic Vessels

The lymphatic system (LS), a body-wide network of vessels and lymphoid organs governing fluid homeostasis and immune surveillance, has so far not been investigated as a domain for diagnostic and therapeutic molecular communications (MC) applications, despite several properties that make it a promising, complementary alternative to the cardiovascular system. These favorable properties include slower flow, simpler and less dense molecular fluid composition, and direct anatomical access to lymph nodes. Realizing this potential, however, requires a quantitative understanding of how solutes propagate through the LS, a problem that, unlike lymph flow itself, remains largely unaddressed in the literature. As a first step towards narrowing this gap, we develop a particle-based simulation (PBS) framework of solute transport through a three-dimensional chain of valve-separated, concatenated vessel segments, called lymphangions. We simulate the spatiotemporal evolution of solute concentration and qualitatively validate the resulting transport dynamics against existing in vivo measurements of fluorescent tracer propagation in multi-lymphangion lymphatic vessels. Our simulations show that the valve-gated nature of solute transport in lymphatic vessels leads to bursty solute concentrations over time, a characteristic that can also be observed in vivo. Additionally, we find that, within one pumping period, peak timing is dictated by the valves' synchronizing effect rather than the particle release time, while diffusivity and receiver placement determine peak sharpness. Overall, the proposed PBS framework provides a first quantitative basis for solute transport modeling in the LS and several concrete application scenarios for MC in this underexplored domain. Supplementary video material illustrating the PBS is publicly available on Zenodo [DOI: 10.5281/zenodo.21888066].

q-bio.TO↗

arXiv2026

A Combined ODE Model of Carbohydrate Fermentation and Colorectal Cancer

We formulate and analyze a system of non-linear ordinary differential equations that describe key metabolic and immunological interactions between butyrate produced by fiber-fermenting gut microbiota, colorectal cancer cells and host cell populations. The model is studied both independently and in conjunction with a pre-existing carbohydrate fermentation model. The parameter space is explored through sensitivity analyses. Simulation experiments are conducted to illustrate the emergence of varying dynamical behaviour driven by butyrate availability. Our model predicts that butyrate production is driven by fiber consumption and further supported by probiotics in the case of microbial dysbiosis. It also suggests that butyrate may help in suppressing tumour growth. We also show that by adding noise with sufficiently high intensity, cancer elimination occurs almost surely in infinite time and that this threshold level of noise intensity decreases with increasing butyrate concentrations.

q-bio.TO↗

arXiv2026

Intestinal villi and crypt density robustly maximizes nutrient absorption

The villi and crypts of the gastrointestinal tract increase the effective surface area of the intestinal mucosa, potentially enhancing nutrient absorption. It is commonly assumed that this is their primary function, and that a higher villi density necessarily leads to improved absorption. However, when villi are packed too closely together, diffusion can be hindered, potentially offsetting this benefit. In this work, we investigate quantitatively the relationship between the density of these structures and the overall efficiency of absorption. In three different simplified geometries, approximating leaf-like villi, finger-like villi, and colonic crypts, we calculate analytically the concentration profile and the absorption flux, assuming that there is only diffusion between these structures while the lumen is well mixed. When plotting the absorption flux per unit of gut length as a function of the structures' density, we observe that there is a density maximizing absorption. We study numerically this optimum. We find that it is robust to the nutrient absorption properties: a geometry optimal for one nutrient is close to optimum for another nutrient. Physiological data from various animal species fall within this predicted optimal range, consistent with the hypothesis that structure density is shaped by selection for efficient nutrient uptake.

q-bio.TO↗