Nature Reviews Disease Primers最新文献

Peripheral artery disease (PAD) is characterized by blockage of the arteries that supply the lower extremities, often occurring as a result of atherosclerosis and thrombosis. PAD affects approximately 230 million people worldwide, with a growing prevalence owing to population ageing and concomitant cardiovascular risk factors, including smoking, diabetes mellitus, hypertension and dyslipidaemia. Patients with PAD have an increased risk of major cardiovascular and limb events, and substantially poorer walking performance compared with those without PAD. The screening and identification of PAD involves clinical and imaging assessments of disease extent and severity and stratification of individual risk to ensure appropriate management. Patients with PAD should be treated with guideline-directed medical therapy (GDMT), including antithrombotic, lipid-lowering, glucose-lowering and anti-hypertensive therapies, and exercise therapies that aim to improve function as well as cardiovascular and limb outcomes. For patients with compromised limb viability, such as acute and chronic limb-threatening ischaemia, or severe functional impairment that does not improve with exercise training, lower extremity revascularization is recommended. Given the complexity of PAD management, a multidisciplinary vascular team is required to achieve the best individualized treatment. Further research efforts should focus on reducing ischaemic events and health disparities and on optimizing the implementation of GDMT and exercise therapy, as well as improving the quality of life in patients with PAD.

Autoimmune encephalitis (AE) is a treatable neuro-inflammatory disorder that is increasing in incidence. AE can be associated with malignancy (paraneoplastic), but in many patients no tumour is present. The disease presentation of AE can be heterogeneous depending on the type of antibody involved. AE is often caused by neuronal antibodies that bind to extracellular autoantigens (that is, N-methyl-D-aspartate receptor (NMDAR) and LGI1). Binding of these antibodies causes dysfunction of synaptic receptors, which leads to neurological symptoms. In these patients, treatment with immunosuppressive therapies is believed to decrease inflammation and deplete antibodies, and is essential for recovery. AE can also occur in patients with antibodies against intracellular antigens (such as Hu and Ri), often in the setting of malignancy. In these patients, tumour treatment is essential for stabilization or improvement. The most frequent symptoms of AE are cognitive problems, behavioural changes and seizures. Rapid recognition of AE syndromes is essential as earlier treatment of AE leads to better outcomes. For a definite diagnosis, the identification of an autoantibody is essential; however, some patients have seronegative AE. Most patients are severely affected during the acute disease stage, but long-term functional recovery is often good, particularly for patients without cancer. Nevertheless, residual anxiety, fatigue and cognitive problems can considerably affect quality of life. Research focuses on improving the understanding of pathophysiological processes, establishing patient-tailored outcome measures, optimizing treatment prediction models and studying different therapeutic regimens, all aiming to improve treatment and long-term outcomes.

Diabetic retinopathy is a complication of diabetes mellitus that is clinically characterized by changes in retinal microvasculature. Diabetic retinopathy is now better defined as diabetic retinal disease (DRD), as diabetes mellitus affects not only the retinal microvasculature but the whole retina, including neurons and glia. A global concerted effort to study preclinical and clinical signs of DRD and their association with visual acuity and patient-reported vision-related quality of life, and the integration of these features with systemic health and biochemical milieu in people with diabetes mellitus is underway. The Diabetic Retinopathy Clinical Research Retina Network trials and other researchers have provided substantial robust evidence on the current management of vision-threatening diabetic retinopathy that includes proliferative diabetic retinopathy and diabetic macular oedema. Progress is also being made to develop, evaluate and implement cost-effective strategies for personalized screening, treatment and monitoring, incorporating artificial intelligence as clinical decision support tools, where appropriate. In addition, novel therapies and modes of delivery are being evaluated to increase durability of interventions and improve affordability to improve vision-related quality of life and reduce the global burden of blindness owing to DRD.

Up to 50% of patients with metastatic cancer develop lung metastases during their disease course. Lung metastases are linked to poor prognosis across various cancer types and might impair the quality of life of patients, causing dyspnoea, cough, haemoptysis and pain, potentially diminishing physical, functional and emotional well-being. Lung metastases arise from a complex interplay of tumour-secreted factors such as VEGF, TGFβ and CCL2, which drive vascular remodelling, immune cell recruitment and extracellular matrix reprogramming. Additionally, tumour-derived exosomes and microparticles contribute to organotropism and immunosuppression by altering the lung microenvironment. The ensemble of these modifications creates a pre-metastatic niche conducive to tumour cell colonization and outgrowth. Lung metastases are primarily diagnosed through imaging; histological confirmation is sometimes required to distinguish them from primary lung cancer. The size and number of lung metastases, timing of primary cancer treatment, histology, and the patient's clinical condition are all considered to determine the most appropriate treatment. When a locoregional approach is not possible, histology-based, molecular-driven systemic therapy is the choice. No systemic treatment is currently available specifically for lung metastases. Advances in understanding the distinct stages of pre-metastatic niche formation and lung metastasis outgrowth might lead to the development of prevention strategies and tailored treatments.