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Annual Review of Medicine - Volume 76, 2025
Volume 76, 2025
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The Genetic Basis of Sudden Cardiac Death: From Diagnosis to Emerging Genetic Therapies
Vol. 76 (2025), pp. 283–299More LessSudden cardiac death (SCD) is an abrupt, tragic manifestation of a number of cardiovascular diseases, primarily ion channelopathies and heritable cardiomyopathies. Because these diseases are heritable, genetics play a key role in the diagnosis and management of SCD-predisposing diseases. Historically, genetics have been used to confirm a diagnosis and identify at-risk family members, but a deeper understanding of the genetic causes of SCD could pave the way for individualized therapy, early risk detection, and a transformative shift toward genetically informed therapies. This review focuses on the evolving genetic landscape of SCD-predisposing diseases, the current state of gene therapy and therapeutic development, and the promise of using predictive genetics to identify individuals at risk of SCD.
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RASopathies in Cardiac Disease
Vol. 76 (2025), pp. 301–314More LessRASopathies are a group of clinically overlapping autosomal dominant disorders caused primarily by mutations in genes that reside along the canonical Ras–mitogen-activated protein kinase signaling cascade. Though individually rare, collectively, these disorders constitute one of the largest families of congenital disorders worldwide, particularly for infantile hypertrophic cardiomyopathy. Significantly, despite almost five decades of RASopathy research, therapeutic options remain limited and focused primarily on treating symptoms rather than disease etiology. Targeting the genes causal to these disorders, and the nodal pathways critical for their regulation, however, has been challenging. In this review, we highlight these challenges, particularly with respect to congenital heart defects and cardiac diseases and discuss limitations and future directions for approaches to new therapeutic strategies.
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Hypertension Management in Pregnancy
Vol. 76 (2025), pp. 315–326More LessChronic hypertension and preeclampsia spectrum disorders in pregnancy are important contributors to long-term maternal morbidity and mortality. Due to physiologic changes during pregnancy and the postpartum period, blood pressure expectations differ between primary care providers and obstetricians. The goal of this article is to describe the pathophysiology and definitions of hypertension in the obstetric context and review current evidence for management during pregnancy and the postpartum period. Longitudinal follow-up with a primary care provider after delivery is crucial for long-term cardiovascular risk reduction in hypertensive patients.
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A Rational Approach to the Treatment of Acute Pulmonary Embolism
Vol. 76 (2025), pp. 327–337More LessOver the past decade, new modalities have emerged to treat acute pulmonary embolism (PE). However, PE remains a leading cause of morbidity and mortality worldwide. In the absence of robust clinical trial data and definitive guidelines and recommendations for a variety of clinical situations, individual patient treatment decisions have become paradoxically more challenging as innovation in the space has grown. In this review, we discuss a practical and current approach to patients diagnosed with PE, focusing on their risk stratification and treatment selection.
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Biologic Medications for Severe Asthma: Implications for Understanding Pathogenic Heterogeneity and Endotypes
Vol. 76 (2025), pp. 339–355More LessAsthma is a chronic inflammatory disease of the airways long known for phenotypic heterogeneity. Phenotyping studies in asthma have led to a better characterization of disease pathogenesis, yet further work is needed to pair available treatments with disease endotypes. In this review, the biology of targeted pathways is discussed along with the efficacy of biologic therapies targeting those pathways. Results of asthma clinical trials are included, as well as results of trials in related diseases. This review then analyzes how biologics help to inform the complex immunobiology of asthma and further guide their use while identifying areas for future research.
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Long-Term Risks of Living Kidney Donation: State of the Evidence and Strategies to Resolve Knowledge Gaps
Vol. 76 (2025), pp. 357–372More LessLiving-donor kidney transplantation is the preferred treatment for kidney failure. In the United States, rates of living kidney donation have been stagnant, which is partly related to concerns over medical and financial risks. Recent research has better characterized the risks of living kidney donation, although the field is limited by a lack of robust registries. Available evidence supports small increases in the risks of end-stage kidney disease and hypertensive disorders of pregnancy in living donors. For most donors, the 15-year risk of kidney failure is less than 1%, but for certain populations this risk may be higher. New tools such as genetic kidney disease panels may assist with risk stratification. Living kidney donors generally have similar or improved psychosocial health following donation compared to prior to donation and nondonor experience. Postdonation care allows for preventative care measures to mitigate risk as well as ongoing surveillance of donor outcomes. Continuing efforts to capture and report outcomes of living donation are necessary to safely expand living donation worldwide.
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Update on Hepatorenal Syndrome: From Pathophysiology to Treatment
Vol. 76 (2025), pp. 373–387More LessHepatorenal syndrome–acute kidney injury (HRS-AKI) occurs in the setting of advanced chronic liver disease, portal hypertension, and ascites. HRS-AKI is found in ∼20% of patients presenting to the hospital with AKI, but it may coexist with other causes of AKI and/or with preexisting chronic kidney disease, thereby making the diagnosis challenging. Novel biomarkers such as urinary neutrophil gelatinase–associated lipocalin may be useful. While HRS-AKI is a functional form of AKI related to circulatory and neurohormonal dysfunction, there is increasing recognition of the importance of systemic inflammation and the renal microenvironment. Early diagnosis and initiation of HRS-AKI-specific treatment can improve outcomes. The mainstay of therapy is a vasoconstrictor (terlipressin or norepinephrine) combined with albumin, which achieves resolution of HRS in 40–50% of cases. Liver transplantation is the only option for patients failing to respond to medical therapies.
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Advances in Therapy for Refractory Epilepsy
Vol. 76 (2025), pp. 389–402More LessDrug-resistant epilepsy (DRE) is defined as failure to achieve sustained seizure control with adequate trials of two appropriate antiseizure medications (ASMs). DRE affects one-third of patients with epilepsy and is associated with significant morbidity and mortality. Newer ASMs provide pharmacological therapy that is better tolerated but not necessarily more effective than older ASMs. Resective brain surgery is the gold standard to treat DRE and achieve seizure freedom, with laser ablation offering an alternative with less morbidity but lower effectiveness. For patients who are not candidates for resection or ablation, multiple neuromodulation options can reduce seizure burden. These neuromodulation devices have shown comparable effectiveness in randomized clinical trials, but the results vary in open-label follow-up cohorts, as do the risks of complications and associated costs. Dietary therapies can help, particularly in pediatric genetic epilepsies. Innovative genetic therapy approaches are being pursued, offering the promise of precision medicine.
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Sleep Health Disparities
Vol. 76 (2025), pp. 403–415More LessSleep is an important and potentially modifiable determinant of many severe health outcomes. Sleep health disparities exist and are exemplified by reported differential rates of prevalence, severity, and outcomes among minority groups and low-socioeconomic-status backgrounds. In this review we highlight the concept of sleep health, review the evidence for disparities in sleep health, examine risk factors and consequences of poor sleep health, and discuss policy implications.
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Contemporary Management of Acute Ischemic Stroke
Vol. 76 (2025), pp. 417–429More LessIn the past decade, adding mechanical thrombectomy (MT) of intracranial arterial occlusions to intravenous (IV) thrombolysis has revolutionized the treatment of acute ischemic stroke (AIS) by expanding the therapeutic window to 24 h. Treatment decisions require establishing a high probability of AIS; confirming time since last known well (LKW); assessing severity of the neurological deficit; determining any contraindications to IV thrombolysis; and performing neuroimaging, usually noncontrast computed tomography (NCCT), to exclude intracerebral hemorrhage. If time since LKW is less than 4.5 h, patients with disabling stroke without contraindications can proceed immediately to IV thrombolysis while the decision about MT is under way. For some patients, the MT decision can be made on the basis of clinical assessment, NCCT, and CT angiography showing a large vessel occlusion. Others may require additional neuroimaging. Patients who are not candidates for IV thrombolysis within 4.5 h or MT should be immediately evaluated for eligibility for extended-window IV thrombolysis or early antiplatelet treatment.
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New Approaches to the Treatment of Hypercortisolism
Vol. 76 (2025), pp. 431–445More LessThis review explores the evolving landscape of treatments for hypercortisolism, highlighting both established and emerging therapies. Although surgery remains the cornerstone of management, medical therapies play a crucial and expanding role, especially in cases of persistent, recurrent, or severe hypercortisolism. We discuss the effectiveness and limitations of steroidogenesis inhibitors, pituitary-directed drugs, glucocorticoid receptor antagonists, and experimental drugs targeting novel molecular pathways that have been implicated in the pathogenesis of hypercortisolism. Despite advancements, significant unmet needs persist, underscoring the importance of personalized treatment approaches and the development of targeted therapies. Ongoing and future clinical trials are crucial for validating the safety and efficacy of these innovative treatments in Cushing disease management.
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Previous Volumes
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Volume 76 (2025)
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Volume 75 (2024)
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Volume 74 (2023)
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Volume 73 (2022)
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Volume 72 (2021)
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Volume 71 (2020)
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Volume 70 (2019)
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Volume 69 (2018)
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Volume 68 (2017)
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Volume 67 (2016)
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Volume 66 (2015)
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Volume 65 (2014)
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Volume 64 (2013)
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Volume 63 (2012)
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Volume 62 (2011)
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Volume 61 (2010)
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Volume 60 (2009)
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Volume 59 (2008)
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Volume 58 (2007)
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Volume 57 (2006)
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Volume 56 (2005)
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Volume 55 (2004)
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Volume 54 (2003)
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Volume 53 (2002)
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Volume 52 (2001)
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Volume 51 (2000)
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Volume 50 (1999)
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Volume 49 (1998)
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Volume 48 (1997)
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Volume 47 (1996)
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Volume 46 (1995)
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Volume 45 (1994)
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Volume 44 (1993)
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Volume 43 (1992)
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Volume 42 (1991)
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Volume 41 (1990)
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Volume 40 (1989)
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Volume 39 (1988)
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Volume 38 (1987)
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Volume 37 (1986)
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Volume 36 (1985)
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Volume 35 (1984)
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Volume 34 (1983)
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Volume 33 (1982)
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Volume 32 (1981)
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Volume 31 (1980)
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Volume 30 (1979)
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Volume 29 (1978)
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Volume 28 (1977)
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Volume 27 (1976)
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Volume 26 (1975)
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Volume 25 (1974)
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Volume 24 (1973)
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Volume 23 (1972)
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Volume 22 (1971)
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Volume 21 (1970)
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Volume 20 (1969)
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Volume 19 (1968)
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Volume 18 (1967)
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Volume 17 (1966)
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Volume 16 (1965)
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Volume 15 (1964)
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Volume 14 (1963)
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Volume 13 (1962)
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Volume 12 (1961)
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Volume 11 (1960)
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Volume 10 (1959)
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Volume 9 (1958)
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Volume 8 (1957)
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Volume 7 (1956)
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Volume 6 (1955)
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Volume 5 (1954)
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Volume 4 (1953)
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Volume 3 (1952)
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Volume 2 (1951)
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Volume 1 (1950)
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Volume 0 (1932)