Induced pluripotent stem cells (iPSCs), obtained by reprogramming different somatic cell types, represent a promising tool for the study of drug toxicities, especially in the context of personalized medicine. Indeed, these cells retain the same genetic heritage of the donor, allowing the development of personalized models. In addition, they represent a useful tool for the study of adverse drug reactions (ADRs) in special populations, such as pediatric patients, which are often poorly represented in clinical trials due to ethical issues. Particularly, iPSCs can be differentiated into any tissue of the human body, following several protocols which use different stimuli to induce specific differentiation processes. Differentiated cells also maintain the genetic heritage of the donor, and therefore are suitable for personalized pharmacological studies; moreover, iPSC‐derived differentiated cells are a valuable tool for the investigation of the mechanisms underlying the physiological differentiation processes. iPSCs‐derived organoids represent another important tool for the study of ADRs. Precisely, organoids are in vitro 3D models which better represent the native organ, both from a structural and a functional point of view. Moreover, in the same way as iPSC‐derived 2D models, iPSC‐derived organoids are appropriate personalized models since they retain the genetic heritage of the donor. In comparison to other in vitro models, iPSC‐derived organoids present advantages in terms of versatility, patient‐specificity, and ethical issues. This review aims to provide an updated report of the employment of iPSCs, and 2D and 3D models derived from these, for the study of ADRs.This article is categorized under: Cancer > Stem Cells and Development

1. Severe asthma (SA) is a heterogeneous and debilitating condition, often associated with a high burden of exacerbations, dependence on oral corticosteroids (OCS), and poor quality of life [1–3]. ...

Background: “Remission” is a primary therapeutic goal in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), though definitions vary regarding olfactory function. We evaluated “Dual Remission” kinetics in patients treated with dupilumab over 24 months. Methods: This single-center retrospective study analyzed 28 patients with comorbid severe asthma and CRSwNP. Dual Remission was defined as simultaneous asthma remission (ACT ≥ 20, no exacerbations, no OCS and stable lung function) and CRSwNP remission (SNOT-22 < 40, NPS ≤ 1). We additionally analyzed “Complete Recovery” by applying a stricter composite definition requiring the restoration of normosmia (Sniffin’ Sticks score ≥ 12). Results: At baseline, patients exhibited uncontrolled disease (median ACT 19, NPS 6). Treatment led to rapid asthma remission (85.7% at 12 months, 100% at 24 months). CRSwNP remission was slower but progressive, rising from 57% at 12 months to 88% at 24 months, demonstrating a significant “catch-up” phenomenon. Consequently, Dual Remission rates increased from 54% to 88% by month 24. When applying the stricter “Complete Recovery” criteria requiring normosmia, only 32% met the goal. Conclusion: Dupilumab is highly effective, enabling 88% of patients to achieve Dual Remission after 24 months. However, full olfactory restitution is distinct from structural polyp regression and harder to achieve, likely due to persistent neuroepithelial damage.

Background: "Remission" is a primary therapeutic goal in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), though definitions vary regarding olfactory function. We evaluated "Dual Remission" kinetics in patients treated with dupilumab over 24 months. Methods: This single-center retrospective study analyzed 28 patients with comorbid severe asthma and CRSwNP. Dual Remission was defined as simultaneous asthma remission (ACT ≥ 20, no exacerbations, no OCS) and CRSwNP remission (SNOT-22 < 40, NPS ≤ 1). We additionally analyzed "Complete Recovery" by applying a stricter composite definition requiring the restoration of normosmia (Sniffin’ Sticks score ≥ 12). Results: At baseline, patients exhibited uncontrolled disease (median ACT 19, NPS 6). Treatment led to rapid asthma remission (85.7% at 12 months, 100% at 24 months). CRSwNP remission was slower but progressive, rising from 57% at 12 months to 88% at 24 months, demonstrating a significant "catch-up" phenomenon. Consequently, Dual Remission rates increased from 54% to 88% by month 24. However, when requiring normosmia for "Complete Recovery," only 32% met the criteria, revealing that 56% achieved clinical silence yet remained hyposmic. Conclusion: Dupilumab is highly effective, enabling 88% of patients to achieve Dual Remission after 24 months. However, full olfactory restitution is distinct from structural polyp regression and harder to achieve, likely due to persistent neuroepithelial damage.

Extended anticoagulation is recommended in subjects with cancer-associated thrombosis (CAT). The API-CAT trial showed that reduced-dose apixaban is noninferior to full-dose for preventing recurrent venous thromboembolism (VTE), but the generalizability of these findings to real-world populations remains to be determined. We conducted a multicenter retrospective cohort study including patients with CAT receiving extended direct oral anticoagulants (DOACs) at full or reduced dose, after at least 6 months of anticoagulation. The primary efficacy outcome was recurrent VTE. The primary safety outcome was major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). A total of 603 patients were included, of whom 381 (63.2%) received reduced-dose and 222 (36.8%) full-dose DOACs. During a median follow-up of 335 days, recurrent VTE occurred in 3.9% of patients in the reduced-dose and 2.7% in the full-dose group (p=0.4). MB occurred in 1.0% and 0.9% (p=0.9), and CRNMB in 4.7% and 5.4% (p=0.7), respectively. In adjusted analyses, reduced-dose DOACs were associated with a non-significant increase in VTE recurrence (hazard ratio 1.4, 95% CI 0.5–3.7), with no differences in bleeding outcomes. In this multicenter real-world cohort, reduced-dose DOACs were associated with low rates of recurrent VTE and bleeding, comparable to those observed with full-dose regimens. These findings suggest that reduced-dose anticoagulation may be a feasible option in selected patients with CAT requiring extended treatment, supporting individualized decision-making. Further studies are needed to better define optimal dose selection in this setting.