Lodovica Zullo, Dimitris Filippiadis, Lizza E L Hendriks, Daniel Portik, Jonathan D Spicer, Ignacio I Wistuba, Benjamin Besse
{"title":"Lung metastases.","authors":"Lodovica Zullo, Dimitris Filippiadis, Lizza E L Hendriks, Daniel Portik, Jonathan D Spicer, Ignacio I Wistuba, Benjamin Besse","doi":"10.1038/s41572-025-00642-1","DOIUrl":"https://doi.org/10.1038/s41572-025-00642-1","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"60"},"PeriodicalIF":76.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alessia Argirò, Victoria Parikh, Ruxandra Jurcut, Gherardo Finocchiaro, Juan Pablo Kaski, Eric Adler, Iacopo Olivotto
{"title":"Hypertrophic cardiomyopathy.","authors":"Alessia Argirò, Victoria Parikh, Ruxandra Jurcut, Gherardo Finocchiaro, Juan Pablo Kaski, Eric Adler, Iacopo Olivotto","doi":"10.1038/s41572-025-00643-0","DOIUrl":"10.1038/s41572-025-00643-0","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and represents a leading cause of morbidity and mortality. HCM is a sarcomeric disease characterized by genetically determined defects in sarcomere proteins, leading to left ventricular hypertrophy, hypercontractility and diastolic dysfunction. The phenotypic spectrum of the disease is heterogeneous, ranging from mild forms that can remain stable and asymptomatic for many years, through to childhood-onset, severe cases that can result in progressive heart failure and ventricular arrhythmias. Multi-imaging techniques including echocardiography and cardiac magnetic resonance are pivotal for diagnostic and prognostic assessment in HCM. For decades, therapeutic approaches were limited to invasive septal reduction therapies and nonspecific pharmacological treatment for heart failure. In the last 10 years, however, an in-depth understanding of the pathological mechanisms of HCM has led to the development of targeted therapies, such as myosin inhibitors, which have proven to be safe and effective in improving functional capacity and reducing symptoms. Innovative therapeutic approaches, such as gene therapies that aim to target the genetic variants underpinning the condition, are currently under investigation.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"58"},"PeriodicalIF":76.9,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dean A Fennell, Yoshitaka Sekido, Paul Baas, Aliya N Husain, Alessandra Curioni-Fontecedro, Eric Lim, Isabelle Opitz, Charles B Simone, Fraser Brims, Martin Chi-Sang Wong
{"title":"Pleural mesothelioma.","authors":"Dean A Fennell, Yoshitaka Sekido, Paul Baas, Aliya N Husain, Alessandra Curioni-Fontecedro, Eric Lim, Isabelle Opitz, Charles B Simone, Fraser Brims, Martin Chi-Sang Wong","doi":"10.1038/s41572-025-00640-3","DOIUrl":"10.1038/s41572-025-00640-3","url":null,"abstract":"<p><p>Mesothelioma is a lethal cancer caused by exposure to asbestos, which arises predominantly in the pleural lining of the thoracic cavity or, less commonly, in the peritoneum, pericardium or tunica vaginalis. The incidence of mesothelioma increased globally during the late twentieth century, correlating with the use of asbestos, and it continues to rise in some regions. Asbestos tumorigenesis involves fibre persistence that leads to DNA damage mediated by chronic inflammation. The genomic landscape of mesothelioma is predominantly characterized by tumour suppressor alterations, most frequently occurring in BAP1, CDKN2A, CDKN2B, MTAP, NF2 and TP53. Patients with mesothelioma commonly present with fatigue, dyspnoea and/or cough caused by pleural effusion, pain and reduced appetite with weight loss. Imaging, cytology, histology and immunohistochemistry are used in diagnosis and support tumour staging. Genetic tests are relevant to reveal disease predispositions. Mesotheliomas are classified on the basis of histology into three distinct subtypes: epithelioid (the most common subtype with the best prognosis), biphasic and sarcomatoid (worst prognosis). Chemotherapy has been the standard of care for the past two decades but immune checkpoint inhibition targeting PD1 and CTLA4 is now considered to be the first-line treatment, showing improvement compared with chemotherapy. Few randomized trials have investigated the role of surgery and radiotherapy and none has found a clear benefit over systemic therapies. Mesothelioma is associated with considerable negative effects on quality of life in physical and emotional domains and also substantially affects patients' families and caregivers.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"56"},"PeriodicalIF":76.9,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144799709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Syed Faisal Ahmed, Kate Armstrong, Earl Y Cheng, Martine Cools, Vincent Harley, Berenice B Mendonca, Anna Nordenström, Rodolfo Rey, David E Sandberg, Agustini Utari, Christa E Flück
{"title":"Differences of sex development.","authors":"Syed Faisal Ahmed, Kate Armstrong, Earl Y Cheng, Martine Cools, Vincent Harley, Berenice B Mendonca, Anna Nordenström, Rodolfo Rey, David E Sandberg, Agustini Utari, Christa E Flück","doi":"10.1038/s41572-025-00637-y","DOIUrl":"https://doi.org/10.1038/s41572-025-00637-y","url":null,"abstract":"<p><p>Differences of sex development (DSD) represent a group of congenital conditions that affect human sex development and maturation owing to discrepancies of chromosomal, gonadal and phenotypic sex. The Chicago consensus classifies DSD as sex chromosome DSD, 46,XY DSD and 46,XX DSD, with subclassifications according to gonadal determination into testes and ovaries and hormone-dependent differentiation of Müllerian and Wolffian embryonic structures into female-typical or male-typical internal and external sex organs. DSD may occur as an isolated condition or as part of a complex syndrome. Diagnosis is based on clinical characteristics, imaging studies, hormonal measurements and genetic investigations. Management includes lifelong psychosocial support, hormonal treatments and surgical interventions that require personalization for each case as DSD encompasses a wide variety of aetiologies and presentations. This personalization must also consider individual values and preferences to ensure that clinical care is tailored to meet the unique needs and circumstances of each person, ideally provided by a care team with diverse specialities. This care involves psycho-educational counselling on the condition and its consequences, considering family and cultural norms. Additional efforts are needed to bridge gaps in knowledge related to diagnosis, management and long-term outcomes. Enhancing our understanding of the distinctions between sex and gender in societies is essential as greater awareness will inform and enrich public debates.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"54"},"PeriodicalIF":76.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differences of sex development.","authors":"","doi":"10.1038/s41572-025-00644-z","DOIUrl":"https://doi.org/10.1038/s41572-025-00644-z","url":null,"abstract":"","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"55"},"PeriodicalIF":76.9,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144760535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elton Dajti, Valeria Tripodi, Yayi Hu, Maria Cecilia Estiù, Dan Shan, Giuseppe Mazzella, Francesco Azzaroli
{"title":"Intrahepatic cholestasis of pregnancy.","authors":"Elton Dajti, Valeria Tripodi, Yayi Hu, Maria Cecilia Estiù, Dan Shan, Giuseppe Mazzella, Francesco Azzaroli","doi":"10.1038/s41572-025-00633-2","DOIUrl":"https://doi.org/10.1038/s41572-025-00633-2","url":null,"abstract":"<p><p>Intrahepatic cholestasis of pregnancy is the most common pregnancy-related liver disease, manifesting typically during the third trimester of pregnancy with pruritus and elevated serum bile acids. This condition is associated with increased fetal morbidity and mortality, and its pathogenesis is still incompletely understood, but is most likely multifactorial, involving ethnicity, genetics, hormones and environmental factors. Available evidence covering the pathophysiology of both maternal and fetal manifestations, and potential new areas of interest such as microbiota and the environment, have been reviewed, as well as available biomarkers that can be used particularly with regard to genetics, multiomics and the possible use of machine learning algorithms to predict intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid is still the mainstay of therapy with limited alternative options; however, a new class of drugs inhibiting intestinal bile acid transport might be on the horizon. Intrahepatic cholestasis of pregnancy is still not completely understood, warranting a critical appraisal of its epidemiology, pathogenesis, diagnosis and management.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"11 1","pages":"51"},"PeriodicalIF":76.9,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
求助内容：
应助结果提醒方式：