Scott C Howard, Anna Avagyan, Biruh Workeneh, Ching-Hon Pui
{"title":"Tumour lysis syndrome.","authors":"Scott C Howard, Anna Avagyan, Biruh Workeneh, Ching-Hon Pui","doi":"10.1038/s41572-024-00542-w","DOIUrl":"10.1038/s41572-024-00542-w","url":null,"abstract":"<p><p>Tumour lysis syndrome (TLS) represents a critical oncological emergency characterized by extensive tumour cell breakdown, leading to the swift release of intracellular contents into the systemic circulation, outpacing homeostatic mechanisms. This process results in hyperuricaemia (a by-product of intracellular DNA release), hyperkalaemia, hyperphosphataemia, hypocalcaemia and the accumulation of xanthine. These electrolyte and metabolic imbalances pose a significant risk of acute kidney injury, cardiac arrhythmias, seizures, multiorgan failure and, rarely, death. While TLS can occur spontaneously, it usually arises shortly after the initiation of effective treatment, particularly in patients with a large cancer cell mass (defined as ≥500 g or ≥300 g/m<sup>2</sup> of body surface area in children). To prevent TLS, close monitoring and hydration to improve renal perfusion and urine output and to minimize uric acid or calcium phosphate precipitation in renal tubules are essential. Intervention is based on the risk of a patient of having TLS and can include rasburicase and allopurinol. Xanthine, typically enzymatically converted to uric acid, can accumulate when xanthine oxidases, such as allopurinol, are administered during TLS management. Whether measurement of xanthine is clinically useful to optimize the use of allopurinol or rasburicase remains to be determined.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"10 1","pages":"58"},"PeriodicalIF":76.9,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142036447","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}
Carine E Hamo, Colette DeJong, Nick Hartshorne-Evans, Lars H Lund, Sanjiv J Shah, Scott Solomon, Carolyn S P Lam
{"title":"Heart failure with preserved ejection fraction.","authors":"Carine E Hamo, Colette DeJong, Nick Hartshorne-Evans, Lars H Lund, Sanjiv J Shah, Scott Solomon, Carolyn S P Lam","doi":"10.1038/s41572-024-00540-y","DOIUrl":"https://doi.org/10.1038/s41572-024-00540-y","url":null,"abstract":"<p><p>Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and has a prevalence that is expected to rise with the growing ageing population. HFpEF is associated with significant morbidity and mortality. Specific HFpEF risk factors include age, diabetes, hypertension, obesity and atrial fibrillation. Haemodynamic contributions to HFpEF include changes in left ventricular structure, diastolic and systolic dysfunction, left atrial myopathy, pulmonary hypertension, right ventricular dysfunction, chronotropic incompetence, and vascular dysfunction. Inflammation, fibrosis, impaired nitric oxide signalling, sarcomere dysfunction, and mitochondrial and metabolic defects contribute to the cellular and molecular changes observed in HFpEF. HFpEF impacts multiple organ systems beyond the heart, including the skeletal muscle, peripheral vasculature, lungs, kidneys and brain. The diagnosis of HFpEF can be made in individuals with signs and symptoms of heart failure with abnormality in natriuretic peptide levels or evidence of cardiopulmonary congestion, facilitated by the use of HFpEF risk scores and additional imaging and testing with the exclusion of HFpEF mimics. Management includes initiation of guideline-directed medical therapy and management of comorbidities. Given the significant impact of HFpEF on quality of life, future research efforts should include a particular focus on how patients can live better with this disease.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"10 1","pages":"55"},"PeriodicalIF":76.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982796","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}
Marcus A Mall, Pierre-Régis Burgel, Carlo Castellani, Jane C Davies, Matthias Salathe, Jennifer L Taylor-Cousar
{"title":"Cystic fibrosis.","authors":"Marcus A Mall, Pierre-Régis Burgel, Carlo Castellani, Jane C Davies, Matthias Salathe, Jennifer L Taylor-Cousar","doi":"10.1038/s41572-024-00538-6","DOIUrl":"10.1038/s41572-024-00538-6","url":null,"abstract":"<p><p>Cystic fibrosis is a rare genetic disease caused by mutations in CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). The discovery of CFTR in 1989 has enabled the unravelling of disease mechanisms and, more recently, the development of CFTR-directed therapeutics that target the underlying molecular defect. The CFTR protein functions as an ion channel that is crucial for correct ion and fluid transport across epithelial cells lining the airways and other organs. Consequently, CFTR dysfunction causes a complex multi-organ disease but, to date, most of the morbidity and mortality in people with cystic fibrosis is due to muco-obstructive lung disease. Cystic fibrosis care has long been limited to treating symptoms using nutritional support, airway clearance techniques and antibiotics to suppress airway infection. The widespread implementation of newborn screening for cystic fibrosis and the introduction of a highly effective triple combination CFTR modulator therapy that has unprecedented clinical benefits in up to 90% of genetically eligible people with cystic fibrosis has fundamentally changed the therapeutic landscape and improved prognosis. However, people with cystic fibrosis who are not eligible based on their CFTR genotype or who live in countries where they do not have access to this breakthrough therapy remain with a high unmet medical need.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"10 1","pages":"53"},"PeriodicalIF":76.9,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907083","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}
Omid Seidizadeh, Jeroen C J Eikenboom, Cécile V Denis, Veronica H Flood, Paula James, Peter J Lenting, Luciano Baronciani, James S O'Donnell, David Lillicrap, Flora Peyvandi
{"title":"von Willebrand disease.","authors":"Omid Seidizadeh, Jeroen C J Eikenboom, Cécile V Denis, Veronica H Flood, Paula James, Peter J Lenting, Luciano Baronciani, James S O'Donnell, David Lillicrap, Flora Peyvandi","doi":"10.1038/s41572-024-00536-8","DOIUrl":"10.1038/s41572-024-00536-8","url":null,"abstract":"<p><p>von Willebrand disease (VWD) is the most common inherited bleeding disorder. The disorder is characterized by excessive mucocutaneous bleeding. The most common bleeding manifestations of this condition include nosebleeds, bruising, bleeding from minor wounds, menorrhagia or postpartum bleeding in women as well as bleeding after surgery. Other less frequent symptoms include gastrointestinal bleeding, haematomas or haemarthroses. VWD pathophysiology is complex and results from defects in von Willebrand factor (VWF) glycoprotein. Quantitative deficiencies are responsible for type 1 VWD with a partial decrease of VWF and type 3 with the complete absence of VWF. Qualitative abnormalities cause type 2 VWD, being further divided into types 2A, 2B, 2M and 2N. Although common, VWD is at risk of misdiagnosis, overdiagnosis and underdiagnosis owing to several factors, including complex diagnosis, variability of bleeding symptoms, presence of external variables (blood groups and other physiological modifiers such as exercise, thyroid hormones, oestrogens, and ageing), and lack of disease awareness among non-specialist health-care providers. Establishing the correct VWD diagnosis requires an array of specialized phenotypic assays and/or molecular genetic testing of the VWF gene. The management of bleeding includes increasing endogenous VWF levels with desmopressin or infusion of exogenous VWF concentrates (plasma-derived or recombinant). Fibrinolytic inhibitors, topical haemostatic agents and hormonal therapies are used as effective adjunctive measures.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"10 1","pages":"51"},"PeriodicalIF":76.9,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759885","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}
Dusan Hirjak, Jonathan P Rogers, Robert Christian Wolf, Katharina Maria Kubera, Stefan Fritze, Jo Ellen Wilson, Fabio Sambataro, Gregory Fricchione, Andreas Meyer-Lindenberg, Gabor S Ungvari, Georg Northoff
{"title":"Catatonia.","authors":"Dusan Hirjak, Jonathan P Rogers, Robert Christian Wolf, Katharina Maria Kubera, Stefan Fritze, Jo Ellen Wilson, Fabio Sambataro, Gregory Fricchione, Andreas Meyer-Lindenberg, Gabor S Ungvari, Georg Northoff","doi":"10.1038/s41572-024-00534-w","DOIUrl":"https://doi.org/10.1038/s41572-024-00534-w","url":null,"abstract":"<p><p>Catatonia is a neuropsychiatric disorder characterized by motor, affective and cognitive-behavioural signs, which lasts from hours to days. Intensive research over the past two decades has led to catatonia being recognized as an independent diagnosis in the International Classification of Diseases, 11th Revision (ICD-11) since 2022. Catatonia is found in 5-18% of inpatients on psychiatric units and 3.3% of inpatients on medical units. However, in an unknown number of patients, catatonia remains unrecognized and these patients are at risk of life-threatening complications. Hence, recognizing the symptoms of catatonia early is crucial to initiate appropriate treatment to achieve a favourable outcome. Benzodiazepines such as lorazepam and diazepam, electroconvulsive therapy, and N-methyl-D-aspartate antagonists such as amantadine and memantine, are the cornerstones of catatonia therapy. In addition, dopamine-modulating second-generation antipsychotics (for example, clozapine and aripiprazole) are effective in some patient populations. Early and appropriate treatment combined with new screening assessments has the potential to reduce the high morbidity and mortality associated with catatonia in psychiatric and non-psychiatric settings.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"10 1","pages":"49"},"PeriodicalIF":76.9,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141724011","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}
Paul K. H. Tam, Rebecca G. Wells, Clara S. M. Tang, Vincent C. H. Lui, Maria Hukkinen, Carlos D. Luque, Paolo De Coppi, Cara L. Mack, Mikko Pakarinen, Mark Davenport
{"title":"Biliary atresia","authors":"Paul K. H. Tam, Rebecca G. Wells, Clara S. M. Tang, Vincent C. H. Lui, Maria Hukkinen, Carlos D. Luque, Paolo De Coppi, Cara L. Mack, Mikko Pakarinen, Mark Davenport","doi":"10.1038/s41572-024-00533-x","DOIUrl":"https://doi.org/10.1038/s41572-024-00533-x","url":null,"abstract":"<p>Biliary atresia (BA) is a progressive inflammatory fibrosclerosing disease of the biliary system and a major cause of neonatal cholestasis. It affects 1:5,000–20,000 live births, with the highest incidence in Asia. The pathogenesis is still unknown, but emerging research suggests a role for ciliary dysfunction, redox stress and hypoxia. The study of the underlying mechanisms can be conceptualized along the likely prenatal timing of an initial insult and the distinction between the injury and prenatal and postnatal responses to injury. Although still speculative, these emerging concepts, new diagnostic tools and early diagnosis might enable neoadjuvant therapy (possibly aimed at oxidative stress) before a Kasai portoenterostomy (KPE). This is particularly important, as timely KPE restores bile flow in only 50–75% of patients of whom many subsequently develop cholangitis, portal hypertension and progressive fibrosis; 60–75% of patients require liver transplantation by the age of 18 years. Early diagnosis, multidisciplinary management, centralization of surgery and optimized interventions for complications after KPE lead to better survival. Postoperative corticosteroid use has shown benefits, whereas the role of other adjuvant therapies remains to be evaluated. Continued research to better understand disease mechanisms is necessary to develop innovative treatments, including adjuvant therapies targeting the immune response, regenerative medicine approaches and new clinical tests to improve patient outcomes.</p>","PeriodicalId":18910,"journal":{"name":"Nature Reviews Disease Primers","volume":"38 1","pages":""},"PeriodicalIF":81.5,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141588384","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}
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