Annual review of medicine最新文献

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.

Hepatitis C virus (HCV) is predominantly transmitted through parenteral exposures to infectious blood or body fluids. In 2019, approximately 58 million people worldwide were infected with HCV, and 290,000 deaths occurred due to hepatitis C-related conditions, despite hepatitis C being curable. There are substantial barriers to elimination, including the lack of widespread point-of-care diagnostics, cost of treatment, stigma associated with hepatitis C, and challenges in reaching marginalized populations, such as people who inject drugs. The World Health Organization (WHO) has set goals to eliminate hepatitis C by 2030. Several countries, including Australia, Egypt, Georgia, and Rwanda, have made remarkable progress toward hepatitis C elimination. In the United States, the Biden-Harris administration recently issued a plan for the national elimination of hepatitis C. Global progress has been uneven, however, and will need to accelerate considerably to reach the WHO's 2030 goals. Nevertheless, the global elimination of hepatitis C is within reach and should remain a high public health priority.

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.

There have been several recent advances in the prevention of lower respiratory tract disease (LRTD) due to respiratory syncytial virus (RSV) infection in older adults and young children. Three different vaccines are now approved for use in older adults; one of these vaccines is also approved for use in pregnant individuals for the prevention of LRTD due to RSV in their infants. In addition, a new monoclonal antibody is available to prevent RSV LRTD in infants born during or entering their first RSV season and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season. Despite these advances in prevention efforts, specific antiviral treatment options for RSV infection remain limited. Several promising compounds remain in development.

Chronic pouchitis (CP) occurs in approximately 20% of patients with ulcerative colitis after total proctocolectomy with ileal pouch anal anastomosis and is categorized as antibiotic dependent, antibiotic refractory, or Crohn's disease-like. The management of CP is challenging because of limited evidence and few randomized controlled trials. In this review, we discuss the medical management of CP and its supporting data delineated by type of therapy.

Sudden cardiac death (SCD) is an abrupt, tragic manifestation of a number of cardiovascular diseases, primarily ion channelopathies and heritable cardiomyopathies. Because these diseases are heritable, genetics play a key role in the diagnosis and management of SCD-predisposing diseases. Historically, genetics have been used to confirm a diagnosis and identify at-risk family members, but a deeper understanding of the genetic causes of SCD could pave the way for individualized therapy, early risk detection, and a transformative shift toward genetically informed therapies. This review focuses on the evolving genetic landscape of SCD-predisposing diseases, the current state of gene therapy and therapeutic development, and the promise of using predictive genetics to identify individuals at risk of SCD.

Asthma is a chronic inflammatory disease of the airways long known for phenotypic heterogeneity. Phenotyping studies in asthma have led to a better characterization of disease pathogenesis, yet further work is needed to pair available treatments with disease endotypes. In this review, the biology of targeted pathways is discussed along with the efficacy of biologic therapies targeting those pathways. Results of asthma clinical trials are included, as well as results of trials in related diseases. This review then analyzes how biologics help to inform the complex immunobiology of asthma and further guide their use while identifying areas for future research.

Rapid and accurate triage of patients presenting with chest pain to an emergency department (ED) is critical to prevent ED overcrowding and unnecessary resource use in individuals at low risk of acute myocardial infarction (AMI) and to efficiently and effectively guide patients at high risk to definite therapy. The use of biomarkers for rule-out or rule-in of suspected AMI has evolved substantially over the last several decades. Previously well-established biomarkers have been replaced by cardiac troponin (cTn). High-sensitivity cTn (hs-cTn) assays represent the newest generation of cTn assays and offer tremendous advantages, including improved sensitivity and precision. Still, implementation of these assays in the United States lags behind several other areas of the world. Within this educational review, we discuss the evolution of biomarker testing for detection of myocardial injury, address the specifics of hs-cTn assays and their recommended use within triage algorithms, and highlight potential challenges in their use. Ultimately, we focus on implementation strategies for hs-cTn assays, as they are now clearly ready for prime time.

Membranous nephropathy (MN), an autoimmune kidney disease and leading cause of nephrotic syndrome, leads to kidney failure in up to one-third of affected individuals. Most MN cases are due to an autoimmune reaction against the phospholipase A2 receptor (PLA2R) located on kidney podocytes. Serum PLA2R antibody quantification is now part of routine clinical practice because antibody titers correlate with disease activity and treatment response. Recent advances in target antigen detection have led to the discovery of more than 20 other podocyte antigens, yet the clinical impact of additional antigen detection remains unknown and is under active investigation. Here we review recent findings and hypothesize how current research will inform future care of patients with MN.

The new generation of cancer early detection tests holds remarkable promise for revolutionizing and changing the paradigm of cancer early detection. Dozens of cancer early detection tests are being developed and evaluated. Some are already commercialized and available for use, most as a complement to and not in place of existing recommended cancer screening tests. This review evaluates existing single- and multi-cancer early detection tests (MCEDs), discussing their performance characteristics including sensitivity, specificity, positive and negative predictive values, and accuracy. It also critically looks at the potential harms that could result from these tests, including false positive and negative results, the risk of overdiagnosis and overtreatment, psychological and economic harms, and the risk of widening cancer inequities. We also review the large-scale, population-based studies that are being launched in the United States and United Kingdom to determine the impact of MCEDs on clinically relevant outcomes and implications for current practice.