Annual review of medicine最新文献

CD70 is an emerging target for anticancer therapies. It is an ideal antigen target given its limited expression in normal physiologic tissues and propensity to be aberrantly expressed in a variety of malignancies, thus limiting off-target toxicities. It is also heavily involved in immune homeostasis, and disruption of this pathway can help overcome tumor-related immune cell exhaustion. Recent phase I/II trials using cellular therapies targeting CD70, such as chimeric antigen receptor-T cells, have shown promising effectiveness and safety in treating relapsed or refractory renal cell carcinoma. Noncellular therapies targeting CD70, such as antibody-drug conjugates, monoclonal antibodies, radionuclides, and cytokines, are currently under investigation, with early data showing encouraging results as well. Efforts are already underway to further improve and optimize CD70-based therapies.

Circulating tumor DNA (ctDNA), often referred to as a liquid biopsy, represents a promising biomarker in the management of both localized and advanced solid tumors. It has garnered significant attention due to its potential to inform prognosis and guide therapeutic decisions. The clinical utility of ctDNA spans early cancer detection, minimal residual disease identification, recurrence surveillance, treatment monitoring, and precision oncology treatment decision-making in the advanced setting. Unlike conventional radiological assessments, the short half-life of ctDNA allows for more timely insights into disease dynamics. Several technological approaches are available to measure ctDNA, including next-generation sequencing and droplet digital polymerase chain reaction, although their clinical accuracy depends on multiple biological and technical factors. This review evaluates current evidence surrounding ctDNA's utility in early and advanced solid tumors.

The human microbiome is a sensor and modulator of physiology and homeostasis. Remarkable tractability underpins the promise of therapeutic manipulation of the microbiome. However, the definition of a normal or healthy microbiome has been elusive. This is in part due to the underrepresentation of minority groups and major global regions in microbiome studies to date. We review studies of the microbiome in different populations and highlight a commonality among health-associated microbiome signatures along with major drivers of variation. We also provide an overview of microbiome-associated therapeutic interventions for some widespread, widely studied diseases. We discuss sources of bias and the challenges associated with defining population-specific microbiome reference bases. We propose a roadmap for defining normal microbiome references that can be used for population-customized microbiome therapeutics and diagnostics.

Acid-related disorders represent a significant global health burden. Pharmacological treatment of these conditions has at times been challenged and limited by incomplete effectiveness, antibiotic resistance, adverse medication effects and/or interactions, and disease recurrence. Since the early 1990s, the mainstay of treatment has been proton pump inhibitors (PPIs). Recently, the US Food and Drug Administration issued a clearance for vonoprazan, a potassium-competitive acid blocker (PCAB). PCABs are a new class of acid-suppressing agents that may overcome some of these challenges. The aim of this review is to evaluate and compare the emerging long-term risks of PPI and PCAB therapies.

Drug-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.

Sleep 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.

An altered gut microbiome is a feature of many multifactorial diseases, and microbiome effects on host metabolism, immune function, and possibly neurological function are implicated. Increased biological age is accompanied by a change in the gut microbiome. However, age-related health loss does not occur uniformly across all subjects but rather depends on differential loss of gut commensals and gain of pathobionts. In this article, we summarize the known and possible effects of the gut microbiome on the hallmarks of aging and describe the most plausible mechanisms. Understanding and targeting these factors could lead to prolonging health span by rationally maintaining the gut microbiome.

In this review, we describe how the management of coronary artery disease (CAD) has become increasingly complex due to the rapid evolution of pharmacotherapy and procedural techniques. The expanding array of treatment options has driven researchers to investigate the optimal combination of therapies; while the findings offer invaluable insights, the sheer volume and occasional contradictions can foster confusion. Given the diverse spectrum of CAD and its manifestations, a tailored treatment decision is critical for each patient. We hope to demonstrate that by integrating the key messages from clinical trials and prioritizing patient comprehension and preference, healthcare providers can guide their patients toward appropriate treatment options, ultimately leading to enhanced care.

Depressive disorders present an enormous global public health burden. A notable treatment gap exists between the prevalence of depression and our ability to provide rapid-acting, effective treatment that achieves remission. Brexanolone and zuranolone, the first US Food and Drug Administration-approved drugs for postpartum depression, signify a critical advancement in addressing the unmet needs of a vulnerable patient population. Psilocybin shows promise for treatment-resistant depression and for those who have struggled to find relief with existing treatments. This review discusses transformative therapies that represent significant advancements in postpartum depression, major depressive disorder, and treatment-resistant depression.

Consumption of probiotic products continues to increase, perhaps driven by an interest in gut health. However, the field is filled with controversy, inconsistencies, misuse of terminology, and poor communication. While the probiotic concept is biologically plausible and in some cases mechanistically well established, extrapolation of preclinical results to humans has seldom been proven in well-conducted clinical trials. With noteworthy exceptions, clinical guidance has often been derived not from large, adequately powered clinical trials but rather from comparisons of disparate, small studies with insufficient power to identify the optimal strain. The separation of probiotics from live biotherapeutic products has brought some clarity from a regulatory perspective, but in both cases, consumers should expect scientific rigor and strong supporting evidence for health claims.