Annual review of medicine最新文献

Chronic cough can coexist with or without pulmonary and extrapulmonary conditions and can be refractory to therapies that improve these associated conditions. It is underlined by cough hypersensitivity, which is characterized by increased cough responses to stimuli that affect the airways and vagally innervated tissues as well as by excessive cough responses to innocuous stimuli, and it is caused by neuroinflammatory and neuropathic mechanisms at both peripheral and central levels. The management of chronic cough starts with exclusion of associated conditions, followed by use of neuromodulators and speech and language therapy. This is progressing toward personalized management, with new approaches to endotype to treat these patients with the introduction of novel antitussive therapies.

Cancer immunotherapy has advanced through immune checkpoint inhibitors and T cell therapies, yet challenges persist in overcoming immune evasion. Neoantigen-based vaccines have shown promise, particularly in tumors with high tumor mutation burden. However, logistical barriers and tumor heterogeneity limit their scalability. Shared oncogenic driver mutations (e.g., KRAS, EGFR, IDH) offer a stable and broadly applicable alternative. Clinical trials demonstrate their immunogenicity and potential in minimal residual disease settings. Advances in vaccine delivery and immune modulation, including adjuvants and cytokine-based therapies, may further enhance efficacy. This review explores the evolution of oncogene-directed vaccines, their clinical impact, and future strategies to optimize their therapeutic potential.

Peripheral artery disease (PAD) is a prevalent and underdiagnosed atherosclerotic condition affecting more than 10 million adults in the United States. PAD is a marker of systemic vascular disease and a strong predictor of myocardial infarction, stroke, and mortality. Despite its clinical importance, PAD remains underrecognized due to variable presentation, limitations in screening, and disparities in diagnosis and treatment. This review examines contemporary PAD epidemiology, diagnostic strategies (including the ankle-brachial index), and evidence-based management approaches, from supervised exercise to surgical revascularization. It also highlights the evolving debate on PAD screening guidelines and presents emerging evidence favoring targeted screening in high-risk populations. Importantly, the review explores structural inequities, racial and ethnic disparities, and geographic variation in PAD-related outcomes, particularly amputation. These disparities persist even after adjustment for comorbidities and socioeconomic factors. Addressing PAD effectively requires comprehensive strategies that include early diagnosis, equitable access to care, and policy initiatives.

Chronic kidney disease (CKD) affects 35.5 million US adults, but most patients are unaware of their diagnosis. Screening for CKD at-risk individuals is required, as symptoms do not appear until advanced stages. The combination of urine albumin-to-creatinine ratio and estimated glomerular filtration rate permits the classification of CKD stages and the determination of risk of CKD progression and cardiovascular disease, which is the most common cause of death in CKD. Cardiovascular-kidney-metabolic syndrome highlights the complex interplay between the heart, kidney, and metabolic disorders, such as diabetes and dysfunctional obesity, which promotes chronic inflammation, leading to injury in these organs and systems. New guideline-directed medical therapies consisting of sodium-glucose cotransporter 2 inhibitors, glucose-like peptide-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, in addition to standard-of-care therapies including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, have revolutionized CKD management, which may be best facilitated through a multidisciplinary care approach.

Regulatory T cells (Tregs) accumulate in the tumor microenvironment, where they suppress antitumor immunity and hinder immunotherapy efficacy. Antibody-mediated Treg depletion has emerged as a promising strategy, but its clinical translation has been hampered by incomplete mechanistic understanding, target overlap with effector T cells, and toxicity concerns. This review evaluates key determinants of Treg-depleting therapies, including the choice of target, antibody isotype and engineering, and the Fc gamma receptor landscape that governs effector function. We examine advances in next-generation antibodies targeting CTLA-4, CD25, CCR4, and CCR8, highlighting preclinical insights, early clinical outcomes, and lessons from toxicity profiles. Among next-generation approaches, Fc-optimized anti-CTLA-4 and CCR8 antibodies demonstrate selective intratumoral Treg depletion with partially improved tolerability, fueling progression into phase II/III trials. Continued refinement through novel designs, such as conditionally activated or bispecific antibodies, will be essential to balance efficacy and safety. Together, these strategies hold potential to establish Treg depletion as a viable therapeutic modality in cancer.

Premature ventricular complexes (PVCs) are prevalent arrhythmias and a common reason for cardiac consultation. While often benign, PVCs can be markers of underlying heart disease and result in significant symptoms, left ventricular dysfunction, and in rare cases sudden cardiac death. The evaluation of a patient with PVCs should answer two essential questions: (a) Is the arrhythmia benign or it is a manifestation of a more serious heart condition? (b) Does the patient require specific therapy to suppress the PVCs? This review focuses on risk stratification of patients to identify who may benefit from further evaluation and the clinical scenarios wherein treatment of PVCs should be considered.

Elevated plasma concentration of lipoprotein(a) is a highly prevalent, independent, and causal risk factor for the development of numerous cardiovascular diseases. This review summarizes the key clinical evidence for elevated lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease, aortic stenosis, and abdominal aortic aneurysm. These data are specifically linked to ongoing developments in understanding the pathophysiological mechanisms of lipoprotein(a) in these contexts. Highly potent lipoprotein(a)-lowering therapies are being studied in cardiovascular outcomes trials for their ability to prevent major adverse coronary events and aortic stenosis progression, potentially ushering in a new era of clinical management of lipoprotein(a).

The understanding of myocardial ischemia evolved from early twentieth-century studies showing reversible or irreversible damage depending on ischemia duration. The concept of hibernating myocardium emerged in the 1970s, describing chronically impaired but viable myocardium that could recover after revascularization. Initial observational studies supported revascularization benefits, but randomized trials such as PARR-2, HEART, and STICH showed mixed results, with STICH demonstrating mortality benefits only after extended follow-up. Advances in medical therapy and intervention raised questions about the role of revascularization, leading to recent trials such as ISCHEMIA and REVIVED-BCIS2, which showed limited benefit of revascularization over optimal medical therapy in stable patients.

This review examines the evolving treatment landscape for KRAS-mutant non-small cell lung cancer (NSCLC), along with the significance of KRAS mutations. The development of KRAS G12C inhibitors, such as sotorasib and adagrasib, has changed the treatment landscape for patients with KRAS-mutant NSCLC, overcoming the long-standing challenge of targeting KRAS. However, acquired resistance remains a major hurdle, along with the need for effective therapies for non-G12C KRAS mutations. Ongoing research into next-generation inhibitors and combination strategies aim to improve the clinical outcomes of KRAS-mutant NSCLC patients.

Artificial intelligence (AI) is transforming biomedical research, public health, and clinical care by offering opportunities to improve outcomes and advance health equity. Its promise stems from its ability to analyze complex health data to inform prevention, diagnosis, and treatment. However, concerns are growing that AI may worsen disparities, especially for racial and ethnic minorities, individuals with disabilities, and low-income populations, who often face a higher disease burden. Biased or incomplete data can result in inequitable outcomes. This review highlights strategies for equitable health AI, including applying an equity lens throughout the AI life cycle and meaningfully engaging the communities most affected to ensure that AI enhances outcomes for everyone.