Annual review of medicinePub Date : 2024-01-29Epub Date: 2023-10-12DOI: 10.1146/annurev-med-060622-101239
Matthew Moll, Edwin K Silverman
{"title":"Precision Approaches to Chronic Obstructive Pulmonary Disease Management.","authors":"Matthew Moll, Edwin K Silverman","doi":"10.1146/annurev-med-060622-101239","DOIUrl":"10.1146/annurev-med-060622-101239","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD heterogeneity has hampered progress in developing pharmacotherapies that affect disease progression. This issue can be addressed by precision medicine approaches, which focus on understanding an individual's disease risk, and tailoring management based on pathobiology, environmental exposures, and psychosocial issues. There is an urgent need to identify COPD patients at high risk for poor outcomes and to understand at a mechanistic level why certain individuals are at high risk. Genetics, omics, and network analytic techniques have started to dissect COPD heterogeneity and identify patients with specific pathobiology. Drug repurposing approaches based on biomarkers of specific inflammatory processes (i.e., type 2 inflammation) are promising. As larger data sets, additional omics, and new analytical approaches become available, there will be enormous opportunities to identify high-risk individuals and treat COPD patients based on their specific pathophysiological derangements. These approaches show great promise for risk stratification, early intervention, drug repurposing, and developing novel therapeutic approaches for COPD.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41189361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual review of medicinePub Date : 2024-01-29Epub Date: 2023-09-08DOI: 10.1146/annurev-med-060622-100940
Mahmut S Kaymakci, Kenneth J Warrington, Tanaz A Kermani
{"title":"New Therapeutic Approaches to Large-Vessel Vasculitis.","authors":"Mahmut S Kaymakci, Kenneth J Warrington, Tanaz A Kermani","doi":"10.1146/annurev-med-060622-100940","DOIUrl":"10.1146/annurev-med-060622-100940","url":null,"abstract":"<p><p>Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are large-vessel vasculitides affecting the aorta and its branches. Arterial damage from these diseases may result in ischemic complications, aneurysms, and dissections. Despite their similarities, the management of GCA and TAK differs. Glucocorticoids are used frequently but relapses are common, and glucocorticoid toxicity contributes to significant morbidity. Conventional immunosuppressive therapies can be beneficial in TAK, though their role in the management of GCA remains unclear. Tumor necrosis factor inhibitors improve remission rates and appear to limit vascular damage in TAK; these agents are not beneficial in GCA. Tocilizumab is the first biologic glucocorticoid-sparing agent approved for use in GCA and also appears to be effective in TAK. A better understanding of the pathogenesis of both conditions and the availability of targeted therapies hold much promise for future management.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10557048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual review of medicinePub Date : 2024-01-29Epub Date: 2023-10-03DOI: 10.1146/annurev-med-080122-030714
J P Thornhill, M Gandhi, C Orkin
{"title":"Mpox: The Reemergence of an Old Disease and Inequities.","authors":"J P Thornhill, M Gandhi, C Orkin","doi":"10.1146/annurev-med-080122-030714","DOIUrl":"10.1146/annurev-med-080122-030714","url":null,"abstract":"<p><p>Mpox, previously known as monkeypox, is caused by an <i>Orthopoxvirus</i> related to the variola virus that causes smallpox. Prior to 2022, mpox was considered a zoonotic disease endemic to central and west Africa. Since May 2022, more than 86,000 cases of mpox from 110 countries have been identified across the world, predominantly in men who have sex with men, most often acquired through close physical contact or during sexual activity. The classical clinical presentation of mpox is a prodrome including fever, lethargy, and lymphadenopathy followed by a characteristic vesiculopustular rash. The recent 2022 outbreak included novel presentations of mpox with a predominance of anogenital lesions, mucosal lesions, and other features such as anorectal pain, proctitis, oropharyngeal lesions, tonsillitis, and multiphasic skin lesions. We describe the demographics and clinical spectrum of classical and novel mpox, outlining the potential complications and management.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual review of medicinePub Date : 2024-01-29Epub Date: 2023-10-06DOI: 10.1146/annurev-med-051022-043301
Shradha A Kulkarni, Robert M Wachter
{"title":"The Hospitalist Movement 25 Years Later.","authors":"Shradha A Kulkarni, Robert M Wachter","doi":"10.1146/annurev-med-051022-043301","DOIUrl":"10.1146/annurev-med-051022-043301","url":null,"abstract":"<p><p>Hospitalists are generalists who specialize in the care of hospitalized patients. In the 25 years since the term hospitalist was coined, the field of hospital medicine has grown exponentially and established a substantial footprint in the medical community. There are now more hospitalists than practicing physicians in any other internal medicine subspecialty. Several key forces catalyzed the growth in the field of hospital medicine, including the quality, safety, and value movements; residency duty hour restrictions; the emergence of electronic health records; and the COVID-19 pandemic. Looking ahead, we see new opportunities in the realms of technology and telemedicine, and challenges persist in regard to balancing financial considerations with increasing workload and burnout. Hospitalists must remain nimble and seize emerging opportunities to continue supporting the field's prominence and growth.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41144999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Regulation of Erythropoiesis by the Hypoxia-Inducible Factor Pathway: Effects of Genetic and Pharmacological Perturbations.","authors":"Gregg L Semenza","doi":"10.1146/annurev-med-042921-102602","DOIUrl":"https://doi.org/10.1146/annurev-med-042921-102602","url":null,"abstract":"<p><p>Red blood cells transport O<sub>2</sub> from the lungs to body tissues. Hypoxia stimulates kidney cells to secrete erythropoietin (EPO), which increases red cell mass. Hypoxia-inducible factors (HIFs) mediate <i>EPO</i> gene transcriptional activation. HIF-α subunits are subject to O<sub>2</sub>-dependent prolyl hydroxylation and then bound by the von Hippel-Lindau protein (VHL), which triggers their ubiquitination and proteasomal degradation. Mutations in the genes encoding EPO, EPO receptor, HIF-2α, prolyl hydroxylase domain protein 2 (PHD2), or VHL cause familial erythrocytosis. In addition to O<sub>2</sub>, α-ketoglutarate is a substrate for PHD2, and analogs of α-ketoglutarate inhibit hydroxylase activity. In phase III clinical trials evaluating the treatment of anemia in chronic kidney disease, HIF prolyl hydroxylase inhibitors were as efficacious as darbepoetin alfa in stimulating erythropoiesis. However, safety concerns have arisen that are focused on thromboembolism, which is also a phenotypic manifestation of VHL or HIF-2α mutation, suggesting that these events are on-target effects of HIF prolyl hydroxylase inhibitors.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10668530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cytokine Storm Syndrome.","authors":"Randy Q Cron, Gaurav Goyal, W Winn Chatham","doi":"10.1146/annurev-med-042921-112837","DOIUrl":"https://doi.org/10.1146/annurev-med-042921-112837","url":null,"abstract":"<p><p>Cytokine storm syndrome (CSS), which is frequently fatal, has garnered increased attention with the ongoing coronavirus pandemic. A variety of hyperinflammatory conditions associated with multiorgan system failure can be lumped under the CSS umbrella, including familial hemophagocytic lymphohistiocytosis (HLH) and secondary HLH associated with infections, hematologic malignancies, and autoimmune and autoinflammatory disorders, in which case CSS is termed macrophage activation syndrome (MAS). Various classification and diagnostic CSS criteria exist and include clinical, laboratory, pathologic, and genetic features. Familial HLH results from cytolytic homozygous genetic defects in the perforin pathway employed by cytotoxic CD8 T lymphocytes and natural killer (NK) cells. Similarly, NK cell dysfunction is often present in secondary HLH and MAS, and heterozygous mutations in familial HLH genes are frequently present. Targeting overly active lymphocytes and macrophages with etoposide and glucocorticoids is the standard for treating HLH; however, more targeted and safer anticytokine (e.g., anti-interleukin-1, -6) approaches are gaining traction as effective alternatives.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10663763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual review of medicinePub Date : 2023-01-27Epub Date: 2022-11-14DOI: 10.1146/annurev-med-042921-100438
Jordana B Cohen, Irina Bancos, Jenifer M Brown, Harini Sarathy, Adina F Turcu, Debbie L Cohen
{"title":"Primary Aldosteronism and the Role of Mineralocorticoid Receptor Antagonists for the Heart and Kidneys.","authors":"Jordana B Cohen, Irina Bancos, Jenifer M Brown, Harini Sarathy, Adina F Turcu, Debbie L Cohen","doi":"10.1146/annurev-med-042921-100438","DOIUrl":"10.1146/annurev-med-042921-100438","url":null,"abstract":"<p><p>Primary aldosteronism (PA) is the most common cause of secondary hypertension but is frequently underrecognized and undertreated. Patients with PA are at a markedly increased risk for target organ damage to the heart and kidneys. While patients with unilateral PA can be treated surgically, many patients with PA are not eligible or willing to undergo surgery. Steroidal mineralocorticoid receptor antagonists (MRAs) are highly effective for treating PA and reducing the risk of target organ damage. However, steroidal MRAs are often underprescribed and can be poorly tolerated by some patients due to side effects. Nonsteroidal MRAs reduce adverse renal and cardiovascular outcomes among patients with diabetic kidney disease and are bettertolerated than steroidal MRAs. While their blood pressure-lowering effects remain unclear, these agents may have a potential role in reducing target organ damage in patients with PA.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10670069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Annual review of medicinePub Date : 2023-01-27Epub Date: 2022-10-19DOI: 10.1146/annurev-med-043021-032007
Janet Y Lee, Stephen M Rosenthal
{"title":"Gender-Affirming Care of Transgender and Gender-Diverse Youth: Current Concepts.","authors":"Janet Y Lee, Stephen M Rosenthal","doi":"10.1146/annurev-med-043021-032007","DOIUrl":"10.1146/annurev-med-043021-032007","url":null,"abstract":"<p><p>Increasing numbers of transgender and gender-diverse (TGD) youth, from early puberty through late adolescence, are seeking medical services to bring their physical sex characteristics into alignment with their gender identity-their inner sense of self as male or female or elsewhere on the gender spectrum. Numerous studies, primarily of short- and medium-term duration (up to 6 years), demonstrate the clearly beneficial-even lifesaving-mental health impact of gender-affirming medical care in TGD youth. However, there are significant gaps in knowledge and challenges to such care. Long-term safety and efficacy studies are needed to optimize medical care for TGD youth.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11045042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9263280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Update in Adult Transgender Medicine.","authors":"Alyxandra Ramsay, Joshua D Safer","doi":"10.1146/annurev-med-020222-121106","DOIUrl":"https://doi.org/10.1146/annurev-med-020222-121106","url":null,"abstract":"<p><p>Transgender people often face barriers in health care due to lack of access to care, lack of knowledgeable healthcare professionals, discrimination, and gaps in medical and mental health research. Existing research on transgender health has focused heavily on mental health, HIV/AIDS, sexually transmitted diseases/infections, and substance abuse. Gender-affirming hormone therapy and/or surgery allows for some alignment of biology and gender identity. Gender-affirming care may offer quality-of-life benefits, which may outweigh modest concerns related to exogenous hormone therapy. The Endocrine Society treatment guidelines were revised in 2017, and this article reviews recent data that might inform a future guideline revision. Future longitudinal research is needed to close the gap in knowledge in the field of transgender medicine.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9241618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Multispecific CAR T Cells Deprive Lymphomas of Escape via Antigen Loss.","authors":"Fateeha Furqan, Nirav N Shah","doi":"10.1146/annurev-med-042921-024719","DOIUrl":"https://doi.org/10.1146/annurev-med-042921-024719","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) modified T cell therapy has transformed the management of relapsed/refractory B cell malignancies. Despite high overall response rates, relapse post CAR T treatment remains a clinical challenge. Loss of target antigen, specifically CD19, is one well-defined mechanism of disease relapse. The mechanism of CD19 loss and which patients are at higher risk of CD19 loss remain poorly understood. To overcome CD19 loss, CARs targeting multiple antigens are being tested in clinical trials. CD19/20 and CD19/22 bispecific CARs demonstrate cytotoxicity against CD19-negative cells in preclinical studies. These CARs have also shown efficacy, safety, and a relatively low rate of CD19-negative relapse in phase I trials. These small studies suggest that multispecific CAR T cells can deprive lymphomas of escape via antigen loss. However, the selection of an ideal target, the right CAR construct, and whether these multispecific CARs can induce long-term remissions are still under investigation.</p>","PeriodicalId":8056,"journal":{"name":"Annual review of medicine","volume":null,"pages":null},"PeriodicalIF":10.5,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10678896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}