Annual review of medicine最新文献

Early-onset colorectal cancer (CRC), commonly defined as a CRC diagnosis before 50 years of age, is rapidly increasing. Despite overt symptoms, younger patients with early-onset CRC endure prolonged diagnostic delays. This review urgently delineates the clinical barriers hindering earlier detection by outlining the key steps in the diagnostic pathways, including how symptom recognition and early detection are complicated by patient- and provider-level barriers. We also reiterate challenges and opportunities for improving secondary prevention through screening and primary prevention through lifestyle modification. Advancing early-onset CRC early detection and prevention requires a multipronged approach involving enhanced public awareness, innovation, and coordinated public health efforts.

Glucagon-like peptide 1 receptor (GLP-1R) agonists were originally developed as treatments for diabetes and subsequently evolved into weight management medications. These drugs have recently been shown to demonstrate remarkable efficacy in cardiovascular disease, kidney disease, and heart failure with preserved ejection fraction (HFpEF). In this review, we focus on the cardiovascular protective effects of GLP-1R agonists identified from basic studies and outcome trials, including a brief description of those forthcoming soon.

We take a Paleolithic perspective to account for why nephrolithiasis afflicts so many people and review evidence suggesting that the rapid shift in the human diet 10,000 years ago was a key event that increased stone risk in the modern era. For the past 2 million years, the diet of the hominid family was high in potassium, low in sodium, and high in alkali precursors. A series of technological advances in agriculture, animal husbandry, and industrial-scale food production transformed the human diet to contain more sodium, less potassium, and more acid precursors. This dietary shift was abrupt enough that the kidney was forced to maintain homeostasis at the expense of increasing stone risk. In theory, dietary patterns that resemble the Paleolithic diet should reduce stone risk. Medications like thiazides, alkali, and empagliflozin may improve urinary parameters associated with stone risk, but more clinical trials are needed to test their efficacy for reducing stone recurrence.

The past century has witnessed a paradigm shift in our understanding of the immune system's impact on tumor immunogenicity, outgrowth, and therapy. These advances come not only as a consequence of our enhanced appreciation for the mechanisms underlying immune system function but also because of new experimental technologies that made these advancements possible. Among the most impactful advances has been the development of the field of immunogenomics, which uses next-generation sequencing and predictive algorithms to rapidly identify tumor-specific mutant proteins. These mutant proteins serve as immunotherapy targets, enabling the immune system to differentiate cancer cells from normal cells. The ability to identify these so-called somatic mutation-based tumor neoantigens has led tumor immunologists to explore their efficacy in personalized cancer vaccines, first in mouse tumor models and then in human cancer patients. This review highlights the efforts leading to the discovery and use of tumor- and patient-specific neoantigens, summarizes preclinical and clinical studies that established the efficacy of tumor-specific neoantigen cancer vaccines, discusses challenges and opportunities in the therapeutic use of these vaccines in cancer patients, and summarizes current efforts to render these therapies more generalizable to a larger group of cancer patients.

Diffuse parenchymal lung disease (DPLD) is a group of distinct inflammatory-fibrotic diseases with varied causes, clinical presentations, and outcomes. Complex pathogenesis, patient heterogeneity, and nonspecificity of diagnostic techniques make its management challenging. In the past decade, there have been marked advances in the understanding of the pathophysiology of and management options for DPLD, especially through multidisciplinary collaboration, which has improved the accuracy of diagnosis and aided in personalized treatment strategies, thereby improving patient outcomes. The management of DPLD includes specific therapeutic options, which vary based on the underlying etiology and disease pattern, such as antifibrotics for progressive fibrotic diseases, as well as common strategies focusing on disease monitoring and management of symptoms and comorbidities. This review discusses updates in epidemiology, classification, pathophysiology, and management as well as ongoing research exploring new diagnostic and therapeutic options for different DPLD subtypes.

Peanut allergy is a significant rising public health problem affecting both children and adults. Early peanut introduction has been adopted in multiple westernized nations as a preventative strategic measure to reduce the risk of developing peanut allergy, although implementation faces barriers. Multiple therapies to treat peanut allergy have been developed, including oral immunotherapy and omalizumab as approved treatments to provide protection against reactions from accidental exposure and reduce the risk of anaphylaxis, offering options beyond strict avoidance. Strategies in the developmental pipeline include epicutaneous immunotherapy and sublingual immunotherapy. The future is bright for individuals with peanut allergy, as these breakthroughs can help address the fear, uncertainty, severity, and lack of protection that has become synonymous with this disease. Shared decision-making is needed to ensure that each patient receives the management approach best suited to their needs, preferences, and goals.

Therapeutic targeting of the neuropeptide calcitonin gene-related peptide (CGRP) is a bench-to-bedside success story that has established migraine as a treatable neurological disorder. There are now eight monoclonal antibodies and small-molecule receptor antagonists approved by the US Food and Drug Administration for the acute and preventive treatment of migraine. This review focuses on evolving real-world data for these inhibitors of CGRP activity. While the drugs have been remarkably safe so far, some adverse effects are arising. To conclude, we speculate on the emerging use of CGRP inhibitors for other disorders and what lies on the horizon for combinatorial and neuropeptide-based treatments inspired by the CGRP story.

Kawasaki disease (KD) is an acute, self-limiting vasculitis that primarily affects children under 5 years old. KD manifests as a persistent fever in the presence of mucocutaneous inflammation and lymphadenopathy, which in severe cases leads to the development of coronary artery aneurysms (CAAs). While early intervention with high-dose intravenous immunoglobulin and aspirin significantly lowers the risk of CAAs, up to 20% of patients with KD are resistant to intravenous immunoglobulin and face a substantially higher risk of developing coronary complications, highlighting the urgent need for more effective adjunctive and rescue therapies. Moreover, coronary abnormalities may persist after the apparent resolution of aneurysms, and cardiac complications extend into adolescence and adulthood. Murine models mimicking KD vasculitis have played a pivotal role in advancing our understanding of the disease's immunopathology, shedding light on the immune mechanisms driving its cardiovascular complications. Here, we summarize the current understanding of KD immunopathogenesis and its cardiovascular complications, as well as recent preclinical findings that are facilitating the development of novel therapeutic strategies, offering hope for improved management of KD in the future.

Pulmonary hypertension (PH) is a complex condition characterized by pulmonary vasculopathy and progressive right ventricular dysfunction. Recent advances have reshaped PH management, including refined risk stratification, improved patient phenotyping, and the discovery of novel therapeutics. In alignment with the recommendations of the Seventh World Symposium on Pulmonary Hypertension, we summarize updated treatment strategies and emerging therapies, such as sotatercept, while acknowledging research gaps and areas of clinical equipoise. This practical, evidence-based review explores treatment across all groups of PH to inform clinical decision-making, improve long-term patient outcomes, and address both current and future challenges in PH management.

While traditional antipsychotic drugs provide symptomatic relief for positive symptoms in patients with schizophrenia, many patients are refractory to traditional antipsychotics. Furthermore, these medicines are ineffective in treating negative and cognitive symptoms and have serious adverse effects that limit their utility. Traditional antipsychotics act as antagonists or partial agonists of D₂ dopamine receptors, an action that is key to their antipsychotic efficacy and adverse effects. Muscarinic acetylcholine receptor (mAChR) agonists have now emerged as the first truly novel treatments for schizophrenia. This represents a fundamental breakthrough that provides a new treatment option to reduce psychotic symptoms and possibly improve negative and cognitive symptoms in patients with schizophrenia. Mechanistic studies are shedding light on the specific mAChR subtypes involved and the specific neural circuits where mAChR agonists may exert these effects. These studies may pave the way for a new generation of drugs to treat schizophrenia and other neuropsychiatric disorders.