Human iPSC-derived 3D cardiac models for cardiomyopathies: organoids, spheroids, and engineered heart tissues as translational platforms.

Fatigue is one of the most prevalent and disabling symptoms reported by patients with inflammatory rheumatic diseases (IRDs). In rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren’s disease (SjD; historically referred to as Sjögren’s syndrome) and related inflammatory arthritides, fatigue affects physical activity, cognitive performance, social participation, work capacity and quality of life [–]. Patients frequently describe fatigue as qualitatively different from ordinary tiredness: it may be unpredictable, disproportionate to exertion and only partially relieved by rest. The traditional explanatory model has linked fatigue to systemic inflammation. This model is biologically plausible because cytokines can induce sickness behaviour, alter neurotransmitter function and reduce motivation during acute immune activation [–]. However, routine clinical experience and longitudinal research show that fatigue often persists despite normalized C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), low composite disease activity scores or clinical remission [–, , , ]. Conversely, some patients with objectively active disease report only modest fatigue. This imperfect coupling between inflammation and symptom burden is a major reason why fatigue remains an unmet need in rheumatology. The clinical importance of fatigue extends beyond symptom reporting. Fatigue contributes to impaired physical health, reduced work participation, disability, psychological distress and patient dissatisfaction with care [–]. It also influences how patients interpret disease activity and treatment success. In SLE, for example, fatigue may mediate a substantial proportion of the effect of flares and depression on physical health impairment [, ]. Therefore, fatigue is not merely a secondary complaint but a central patient-reported outcome (PRO) that requires direct assessment and targeted management.