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).

Wastewater-based epidemiology (WBE) is the analysis of wastewater to detect pathogen levels or activity for public health awareness or action. Pioneered in the 1940s, WBE underwent a resurgence during the COVID-19 pandemic, providing important information about number of cases, outbreaks, and seasonal impact. With advancements in detection technologies and growing interest in environmental surveillance, WBE is poised to become a standard practice in public health monitoring. Here, we provide an overview of the current state of the art of pathogen WBE, including methods of molecular detection, analysis of wastewater data, real-world applications and programs, public health interventions, and benefits and challenges for the field.

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.

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.

Postmenopausal osteoporosis is a chronic progressive disease related to estrogen deficiency at menopause, aging, and superimposed genetic and environmental factors. Many patients with osteoporosis are not diagnosed, and the majority are not treated. Current therapies for osteoporosis include antiresorptive treatments, including bisphosphonates, denosumab, and raloxifene, and osteoanabolic treatments, including teriparatide, abaloparatide, and romosozumab, which is a dual-action agent. Sequential therapies aim to optimize fracture prevention and bone density outcomes for long-term management. Recent guidelines have suggested categorical risk stratification and a goal-directed individualized therapy strategy. New treatments under investigation also hold promise for further improving bone health in postmenopausal osteoporosis.

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.

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.

Xenotransplantation of genetically modified pig organs has the potential to change the landscape of transplantation and chronic disease management by providing limitless personalized organs on demand. Decades of progress have resulted in recent US Food and Drug Administration approval for human clinical trials. Understandably, hope for the field is at a maximum, fueled by exciting anecdotal experiences, each providing new insights and questions. While further work is needed before widespread clinical application is plausible, the promise of xenotransplantation has never been more evident. In this review, we seek to highlight recent progress, suggest remaining research questions, and touch on the future of the field.

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 D 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.

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.

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.

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.

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: () Is the arrhythmia benign or it is a manifestation of a more serious heart condition? () 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.

Artificial sweeteners are widely used worldwide, yet their potential health effects remain a topic of debate. Recent studies suggest that artificial sweeteners, both nutritive and nonnutritive, may stimulate appetite, leading to increased caloric intake, a higher body mass index, and a greater risk of obesity. These metabolic changes are associated with an elevated risk of type 2 diabetes and cardiovascular diseases. Moreover, emerging preclinical evidence indicates that artificial sweeteners may influence cancer biology, potentially affecting tumor progression. This review examines the impact of artificial sweeteners on metabolic health, cardiovascular risk, and carcinogenesis, emphasizing the need for further research to clarify their long-term safety and health implications.

Reproducibility concerns in biomedical research have persisted for more than a decade, with large-scale assessments revealing significant challenges in replicating findings. Despite widespread acknowledgment of these issues, responses remain inconsistent, and proposed solutions often lack rigorous evaluation. This review examines the factors that contribute to irreproducibility in conducting, reporting, and reviewing research and assesses the effectiveness and desirability of interventions aimed at improving reproducibility. It highlights the need for balanced scientific reforms that strengthen reproducibility without stifling innovation or introducing unintended consequences. A critical appraisal of the role of meta-research is essential to ensure sustainable improvements in research quality.

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.

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.

Novel biologic therapies in the form of monoclonal antibodies and small molecule kinase inhibitors have transformed the management of several autoimmune, inflammatory, and neoplastic diseases. However, some of these biologics produce complex immunodeficiency states that heighten the risk of opportunistic infections, including invasive fungal infections (IFIs). In this focused review, we outline the antifungal immune defects conferred by novel biologics and discuss the IFIs they predispose to. A better understanding of the immune pathways disrupted by biologics and the IFI susceptibilities they promote should help improve prophylaxis, diagnosis, and treatment for IFIs in patients receiving biologic agents.

Noninvasive tests for colorectal cancer (CRC) screening in average-risk individuals continue to evolve, with the premise of increasing screening participation among eligible individuals. In addition to fecal immunochemical testing (FIT), which has become the noninvasive standard for which to improve sensitivity for detecting CRC and specificity for detecting the absence of CRC, new US Food and Drug Administration-approved tests include the detection of DNA in a next-generation multitarget stool DNA test, the detection of RNA in a multitarget stool RNA test, and blood tests that detect cell-free DNA for genomic alterations, fragmentations, and aberrant methylation, all of which have undergone large clinical trials for effectiveness. Each of these new tests improves upon the CRC sensitivity of FIT but not its specificity. Test sensitivity for CRC detection in persons <50 years of age is comparable to that in persons >50 years. Fecal tests with direct sampling of stool have improved sensitivity for advanced adenomas compared to FIT, but advanced adenoma sensitivity is regressed in blood tests compared to FIT. With about a third of the screening-eligible population not actively screened in the United States, the expansion of the screening-eligible population to include those >45 years of age, the disparity in some populations with lower-than-average screening rates, and the limited colonoscopy screening opportunities due to choice, schedule, availability, or pandemic interruption, these noninvasive tests may fill the gap and rectify CRC screening shortcomings and barriers that colonoscopy alone cannot fill.

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

Oral selective estrogen receptor degraders (SERDs) are pure estrogen receptor antagonists that have the potential to overcome common resistance mechanisms to endocrine therapy in estrogen receptor-positive breast cancer. There are currently five oral SERDs in published and ongoing clinical trials-elacestrant, camizestrant, giredestrant, imlunestrant, and amcenestrant-with more in development. They offer a reasonably well-tolerated oral therapy option with low discontinuation rates in studies. This review summarizes the currently available literature on this new class of drugs.