Annual review of medicine最新文献

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.

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.

For decades, the management of locally advanced rectal cancer has been trimodal therapy with radiotherapy, surgery, and chemotherapy. Collectively, the adoption of total neoadjuvant therapy (TNT), advances in how radiotherapy and chemotherapy are administered, and the introduction of immunotherapy for patients with mismatch repair-deficient tumors have revolutionized the treatment paradigm of locally advanced rectal cancer, most notably by making nonoperative management possible in up to half of patients. Here, we highlight landmark studies that inform the use of TNT. We then discuss ongoing research efforts and future directions in the field with the ultimate goal of improving both survival and quality of life for patients with locally advanced rectal cancer.

Transthyretin amyloid cardiomyopathy (ATTR-CM) has emerged as a significant yet underdiagnosed cause of heart failure. Advancements in the noninvasive imaging that facilitates diagnosis at an earlier stage of disease and treatment have marked a paradigm shift in the management of this previously fatal disease. This review outlines the epidemiology, pathophysiology, diagnosis, and treatment of ATTR-CM, with an emphasis on the recent developments transforming the field, including an ability to diagnose most patients without a biopsy, the shift toward screening or active ascertainment, the development of several new therapies, and a better understanding of how to employ standard heart failure therapies in patients with this disease. Additionally, the review explores questions that have emerged from these developments.

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.

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.

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.

Candida auris is a recently emerged fungal pathogen that causes severe infections in healthcare settings around the globe. A feature that distinguishes C. auris from other fungal pathogens is its high capacity to colonize skin, leading to widespread outbreaks in healthcare facilities via patient-to-patient transmission. C. auris can persist on skin or in the surrounding environment for extended periods of time, and it exhibits greater antifungal resistance than other Candida species. These factors pose major obstacles for the prevention and treatment of C. auris infection. Recent reports have identified frequently colonized skin sites, risk factors for developing invasive infection, and patterns of antifungal resistance among C. auris strains, all of which help guide therapeutic options. In this review, we highlight key studies of C. auris epidemiology and antifungal resistance, discussing how these factors influence healthcare-associated transmission and treatment outcomes.

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.

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.