Annual review of medicine最新文献

The endoscopic evaluation and management of small intestinal diseases continue to evolve and expand. The advent of small bowel wireless capsule endoscopy and deep enteroscopy with either a double- or single-balloon enteroscope now allows complete endoscopic visualization of the entire small intestine and enables access for endoscopic interventions such as biopsies or hemostasis for most of the small bowel. New endoscopic techniques are available to treat proximal malignant small bowel obstruction, including intraluminal stents and endoscopic gastrojejunal stents. Emerging technologies also aim to improve weight loss and diabetes management via small bowel endoscopic interventions.

The population of cancer survivors is on the rise due to an increase in cancer incidence and a decline in cancer mortality. This growing survivor population creates a number of challenges. Although there have been improvements in care planning for cancer survivors, our healthcare system still lacks the delivery of coordinated care between primary care physicians and specialists. Understanding the needs of cancer survivors can help improve the current care models. In this review we describe existing survivorship care models. We also describe emerging models using some programs at the Cleveland Clinic to highlight various potential approaches.

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.

Immune checkpoint blockade targeting the novel targets of the lymphocyte activation gene 3 (LAG3) and the T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibition motif domains (TIGIT) has marked a significant advancement in oncology, offering new therapeutic opportunities to fight diverse malignancies. This review covers the biological basis and clinical application of LAG3 and TIGIT inhibitors, highlighting pivotal trials and therapeutic outcomes. We underscore the use of dual therapy immune checkpoint blockade in enhancing antitumor immunity, particularly in settings where monotherapy has shown limited efficacy. Additionally, we address the emerging challenges such as treatment resistance and adverse effects. We explore the strategic integration of LAG3 and TIGIT blockade within the broader immunotherapy landscape, emphasizing innovative combinations and the quest for predictive biomarkers to optimize patient selection and treatment efficacy.

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.

Monoclonal antibodies (mAbs) targeting the SARS-CoV-2 Spike protein were deployed during the COVID-19 pandemic. While all of the clinically authorized mAbs were eventually defeated by SARS-CoV-2 variants, they were highly effective in preventing disease progression when given early in the course of the disease. The experience with mAbs to SARS-CoV-2 offers important lessons for the use of mAbs in future infectious disease emergencies, such as choosing mAbs that target conserved epitopes and designing cocktails to reduce the emergence of escape variants. Planning for future use must include the creation of infusion centers and the development of strategies to minimize the emergence of escape variants.

Pathogenic variants in BRCA1 and BRCA2 are associated with significantly elevated lifetime risks of breast, ovarian, pancreatic, and prostate cancer. These genes are critical in double-strand break repair through homologous recombination. An understanding of the biology of BRCA1 and BRCA2 led to the development of targeted therapeutics, specifically poly(ADP-ribose) polymerase (PARP) inhibitors, which are approved by the US Food and Drug Administration for multiple BRCA1/2-associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical BRCA1/2 tumors, and we describe novel agents under study.

Chronic hypertension and preeclampsia spectrum disorders in pregnancy are important contributors to long-term maternal morbidity and mortality. Due to physiologic changes during pregnancy and the postpartum period, blood pressure expectations differ between primary care providers and obstetricians. The goal of this article is to describe the pathophysiology and definitions of hypertension in the obstetric context and review current evidence for management during pregnancy and the postpartum period. Longitudinal follow-up with a primary care provider after delivery is crucial for long-term cardiovascular risk reduction in hypertensive patients.

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.

RASopathies are a group of clinically overlapping autosomal dominant disorders caused primarily by mutations in genes that reside along the canonical Ras-mitogen-activated protein kinase signaling cascade. Though individually rare, collectively, these disorders constitute one of the largest families of congenital disorders worldwide, particularly for infantile hypertrophic cardiomyopathy. Significantly, despite almost five decades of RASopathy research, therapeutic options remain limited and focused primarily on treating symptoms rather than disease etiology. Targeting the genes causal to these disorders, and the nodal pathways critical for their regulation, however, has been challenging. In this review, we highlight these challenges, particularly with respect to congenital heart defects and cardiac diseases and discuss limitations and future directions for approaches to new therapeutic strategies.