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Annu Rev Med 2022 01;73:81-93

Department of Internal Medicine, University of Iowa, Iowa City, Iowa, USA; email:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory virus that gains entry via angiotensin-converting enzyme 2 (ACE2) within airway epithelium. Patients exhibit a spectrum of respiratory symptoms from asymptomatic to respiratory failure. Patient factors including obesity, tobacco use, and black race are all associated with increased ACE2 expression and may contribute to increased complications. Read More

Annu Rev Med 2022 01;73:501-515

Texas Children's Hospital, Baylor College of Medicine, Houston, Texas 77030, USA; email:

Several factors, including genetics, family history, diet, physical activity, obesity, and insulin resistance in puberty, appear to increase the risk of type 2 diabetes in youth. Youth-onset type 2 diabetes is often thought of as a single entity but rather exists as a spectrum of disease with differences in presentation, metabolic characteristics, clinical progression, and complication rates. We review what is currently known regarding the risks associated with developing type 2 diabetes in youth. Read More

Annu Rev Med 2022 01;73:339-354

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA; email:

Spontaneous coronary artery dissection (SCAD) is an uncommon but increasingly recognized cause of acute myocardial infarction (MI) among young and middle-aged women and is an important cause of pregnancy-associated MI. Over 90% of SCAD patients are women. Compared to patients with MI caused by atherosclerosis, SCAD patients have fewer cardiovascular risk factors but more often have systemic arteriopathy, most commonly fibromuscular dysplasia. Read More

Annu Rev Med 2022 01;73:183-195

Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA; email:

The last 5 years have seen major shifts in defining whom to test and how to treat infection. Peptic ulcer has changed from a chronic disease to a one-off condition, and countries with a high incidence of gastric cancer have begun implementing population-wide screening and treatment. A proactive approach to testing and treatment of is now recommended, including outreach to family members of individuals diagnosed with active infection as well as high-risk local populations such as immigrants from high-risk countries. Read More

Annu Rev Med 2022 01;73:563-574

Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA; email:

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in , the cystic fibrosis transmembrane conductance regulator gene. People with CF experience a wide variety of medical conditions that affect the pulmonary, endocrine, gastrointestinal, pancreatic, biliary, and reproductive systems. Traditionally, CF carriers, with one defective copy of , were not thought to be at risk for CF-associated diseases. Read More

Annu Rev Med 2022 01;73:307-320

Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, California 94305, USA; email:

We proposed and demonstrated that myelogenous leukemia has a preleukemic phase. In the premalignant phase, normal hematopoietic stem cells (HSCs) gradually accumulate mutations leading to HSC clonal expansion, resulting in the emergence of leukemic stem cells (LSCs). Here, we show that preleukemic HSCs are the basis of clonal hematopoiesis, as well as late-onset blood diseases (chronic-phase chronic myeloid leukemia, myeloproliferative neoplasms, and myelodysplastic disease). Read More

Annu Rev Med 2022 01;73:293-306

Department of Gastroenterology and Hepatology, Amsterdam University Medical Centers, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands; email:

For decades, conventional adenomas were the only known precursor lesions of colorectal cancer (CRC). Accordingly, education and research regarding CRC prevention were mainly focused on adenomas. The groundbreaking discovery that serrated polyps (SPs) also have the potential to develop into CRCs, and seem to account for a considerable proportion of sporadic CRCs, has led to a paradigm shift in the prevention, diagnosis, and treatment of CRC. Read More

Annu Rev Med 2022 01;73:363-375

Division of Cardiology, Hypertrophic Cardiomyopathy Institute, Tufts Medical Center, Boston, Massachusetts 02111; email:

Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited myocardial disorder, transformed over the last several years into a treatable condition with the emergence of effective management options that alter natural history at all ages. Now available are a matured risk stratification algorithm selecting patients for prophylactic implantable defibrillators that prevent arrhythmic sudden death; low-risk, high-benefit surgical myectomy to reverse progressive heart failure symptoms due to left ventricular outflow obstruction; anticoagulation prophylaxis to prevent atrial fibrillation-mediated embolic stroke; and heart transplant for refractory end-stage disease in the absence of obstruction. Those strategies have resulted in reduction of HCM-related morbidity and reduction of mortality to 0. Read More

Annu Rev Med 2022 01;73:575-585

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA; email:

Genetic testing has undergone a revolution in the last decade, particularly with the advent of next-generation sequencing and its associated reductions in costs and increases in efficiencies. The Undiagnosed Diseases Network (UDN) has been a leader in the application of such genomic testing for rare disease diagnosis. This review discusses the current state of genomic testing performed within the UDN, with a focus on the strengths and limitations of whole-exome and whole-genome sequencing in clinical diagnostics and the importance of ongoing data reanalysis. Read More

Annu Rev Med 2022 01 22;73:529-544. Epub 2021 Nov 22.

Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA; email:

Nonalcoholic fatty liver disease (NAFLD) is a major public health crisis affecting approximately 25% of the world's population. The spectrum of NAFLD ranges from bland steatosis to steatohepatitis with fibrosis; eventual development of cirrhosis in a subgroup of patients now represents the leading indication for liver transplant in women and in individuals older than 65. The development of noninvasive liver disease assessment tools has led to substantial progress in the diagnosis of NAFLD. Read More

Annu Rev Med 2022 01 18;73:483-499. Epub 2021 Nov 18.

Department of Clinical Sciences, Lund University/CRC, Skane University Hospital, Malmö 214 28, Sweden; email:

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by insulin deficiency and resultant hyperglycemia. Complex interactions of genetic and environmental factors trigger the onset of autoimmune mechanisms responsible for development of autoimmunity to β cell antigens and subsequent development of T1D. A potential role of virus infections has long been hypothesized, and growing evidence continues to implicate enteroviruses as the most probable triggering viruses. Read More

Annu Rev Med 2022 01 18;73:377-391. Epub 2021 Nov 18.

Institute for Exercise and Environmental Medicine, Texas Health Presbyterian Dallas, and the University of Texas Southwestern Medical Center, Dallas, Texas 75213, USA; email:

The global population is rapidly aging, with predictions of many more people living beyond 85 years. Age-related physiological adaptations predispose to decrements in physical function and functional capacity, the rate of which can be accelerated by chronic disease and prolonged physical inactivity. Decrements in physical function exacerbate the risk of chronic disease, disability, dependency, and frailty with advancing age. Read More

Annu Rev Med 2022 01 17;73:355-362. Epub 2021 Nov 17.

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA; email:

Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. Implantable and wearable cardiac devices have enabled the detection of asymptomatic AF episodes-termed subclinical AF (SCAF). SCAF, the prevalence of which is likely significantly underestimated, is associated with increased cardiovascular and all-cause mortality and a significant stroke risk. Read More

Annu Rev Med 2022 01 9;73:407-421. Epub 2021 Nov 9.

The Clinical Research, Investigation, and Systems Modeling of Acute Illness (CRISMA) Center, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA; email:

Delirium, an acute disturbance in mental status due to another medical condition, is common and morbid in the intensive care unit. Despite its clear association with multiple common risk factors and important outcomes, including mortality and long-term cognitive impairment, both the ultimate causes of and ideal treatments for delirium remain unclear. Studies suggest that neuroinflammation, hypoxia, alterations in energy metabolism, and imbalances in multiple neurotransmitter pathways contribute to delirium, but commonly used treatments (e. Read More

Annu Rev Med 2022 01 26;73:251-265. Epub 2021 Oct 26.

Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; email:

In order to fuel their relentless expansion, cancers must expand their vasculature to augment delivery of oxygen and essential nutrients. The disordered web of irregular vessels that results, however, leaves gaps in oxygen delivery that foster tumor hypoxia. At the same time, tumor cells increase their oxidative metabolism to cope with the energetic demands of proliferation, which further worsens hypoxia due to heightened oxygen consumption. Read More

Annu Rev Med 2022 01 22;73:469-481. Epub 2021 Oct 22.

School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, Arizona 85721, USA.

Type 2 diabetes rates continue to rise unabated, underscoring the need to better understand the etiology and potential therapeutic options available for this disease. The gut microbiome plays a role in glucose homeostasis, and diabetes is associated with alterations in the gut microbiome. Given that consumption of a Western diet is associated with increased metabolic disease, and that a Western diet alters the gut microbiome, it is plausible that changes in the gut microbiota mediate the dysregulation in glucose homeostasis. Read More

Annu Rev Med 2022 01 20;73:213-229. Epub 2021 Oct 20.

Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

Pancreatic neuroendocrine tumors (PNETs) are a heterogeneous and orphan group of neoplasms that vary in their histology, clinical features, prognosis, and management. The treatment of PNETs is highly dependent on the stage at presentation, tumor grade and differentiation, presence of symptoms from hormonal overproduction or from local growth, tumor burden, and rate of progression. The US Food and Drug Administration has recently approved many novel treatments, which have altered decision making and positively impacted the care and prognosis of these patients. Read More

Annu Rev Med 2022 01 20;73:17-39. Epub 2021 Oct 20.

Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. This extraordinary situation prompted entities in government, industry, and academia to work together at unprecedented speed to develop safe and effective vaccines. Indeed, vaccines of multiple types have been generated in record time, and many have been evaluated in clinical trials. Read More

Annu Rev Med 2022 01 20;73:439-453. Epub 2021 Oct 20.

G. Oppenheimer Center for Neurobiology of Stress and Resilience and Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA; email:

Preclinical evidence has firmly established bidirectional interactions among the brain, the gut, and the gut microbiome. Candidate signaling molecules and at least three communication channels have been identified. Communication within this system is nonlinear, is bidirectional with multiple feedback loops, and likely involves interactions between different channels. Read More

Annu Rev Med 2022 01 20;73:545-562. Epub 2021 Oct 20.

Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA; email:

Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease. Since its discovery nearly two decades ago, our understanding of its pathophysiology and clinical manifestations has grown substantially. Early diagnosis and treatment of this elusive disease can prevent substantial organ damage from end-stage fibrosis, emphasizing the need for prompt recognition and accurate characterization of IgG4-RD. Read More

Annu Rev Med 2022 01 19;73:279-292. Epub 2021 Oct 19.

Department of Neurosurgery, Northwestern University, Chicago, Illinois 60611, USA; email:

Faced with unique immunobiology and marked heterogeneity, treatment strategies for glioblastoma require therapeutic approaches that diverge from conventional oncological strategies. The selection and prioritization of targeted and immunotherapeutic strategies will need to carefully consider these features and companion biomarkers developed alongside treatment strategies to identify the appropriate patient populations. Novel clinical trial strategies that interrogate the tumor microenvironment for drug penetration and target engagement will inform go/no-go later-stage clinical studies. Read More

Annu Rev Med 2022 01 13;73:231-250. Epub 2021 Oct 13.

Phase I Clinical Trials Program, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.

Innate immunity and the DNA damage response (DDR) pathway are inextricably linked. Within the DDR, ataxia telangiectasia and Rad3-related (ATR) is a key kinase responsible for sensing replication stress and facilitating DNA repair through checkpoint activation, cell cycle arrest, and promotion of fork recovery. Recent studies have shed light on the immunomodulatory role of the ATR-CHK1 pathway in the tumor microenvironment and the specific effects of ATR inhibition in stimulating an innate immune response. Read More

Annu Rev Med 2022 01 13;73:393-406. Epub 2021 Oct 13.

Department of Medicine, University of Louisville, Louisville, Kentucky 40202, USA; email:

Inhalation of fine particulate matter (PM), produced by the combustion of fossil fuels, is an important risk factor for cardiovascular disease. Exposure to PM has been linked to increases in blood pressure, thrombosis, and insulin resistance. It also induces vascular injury and accelerates atherogenesis. Read More

Annu Rev Med 2022 01 13;73:167-182. Epub 2021 Oct 13.

Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA; email:

Infectious diseases affect individual health and have widespread societal impacts. New ex vivo models are critical to understand pathogenesis, host response, and features necessary to develop preventive and therapeutic treatments. Pluripotent and tissue stem cell-derived organoids provide new tools for the study of human infections. Read More

Annu Rev Med 2022 01 12;73:55-64. Epub 2021 Oct 12.

Departments of Pediatrics and Molecular Virology, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas 77030, USA; email:

The rapid development and deployment of mRNA and adenovirus-vectored vaccines against coronavirus disease 2019 (COVID-19) continue to astound the global scientific community, but these vaccine platforms and production approaches have still not achieved global COVID-19 vaccine equity. Immunizing the billions of people at risk for COVID-19 in the world's low- and middle-income countries (LMICs) still relies on the availability of vaccines produced and scaled through traditional technology approaches. Vaccines based on whole inactivated virus (WIV) and protein-based platforms, as well as protein particle-based vaccines, are the most produced by LMIC vaccine manufacturing strategies. Read More

Annu Rev Med 2022 01 5;73:41-54. Epub 2021 Oct 5.

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA; email:

The worldwide pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the unprecedented pace of development of multiple vaccines. This review evaluates how adenovirus (Ad) vector platforms have been leveraged in response to this pandemic. Ad vectors have been used in the past for vaccines against other viruses, most notably HIV and Ebola, but they never have been produced, distributed, or administered to humans at such a large scale. Read More

Annu Rev Med 2022 01 4;73:267-278. Epub 2021 Oct 4.

Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA; email:

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the third leading cause of cancer-related death worldwide. Single-agent anti-PD-1 immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in early-phase trials, a finding that was not confirmed in phase III studies. The combination of atezolizumab (an anti-PD-L1 ICI) with bevacizumab (an anti-VEGF antibody) was approved as first-line therapy in 2020, however, with significant improvement in response rate, progression-free survival, and overall survival in comparison with the previous standard of care, sorafenib. Read More

Annu Rev Med 2022 01 23;73:455-468. Epub 2021 Sep 23.

Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA; email:

Inflammatory bowel diseases (IBD) arise from a convergence of genetic risk, environmental factors, and gut microbiota, where each is necessary but not sufficient to cause disease. Emerging evidence supports a bidirectional relationship between disease progression and changes in microbiota membership and function. Thus, the study of the gut microbiome and host-microbe interactions should provide critical insights into disease pathogenesis as well as leads for developing microbiome-based diagnostics and interventions for IBD. Read More

Annu Rev Med 2022 01 23;73:423-438. Epub 2021 Sep 23.

Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan 48109, USA; email:

The field of endoscopic bariatric and metabolic therapy has rapidly evolved from offering endoscopic treatment of weight regain following bariatric surgery to providing primary weight loss options as alternatives to pharmacologic and surgical interventions. Gastric devices and remodeling procedures were initially designed to work through a mechanism of volume restriction, leading to earlier satiety and reduced caloric intake. As the field continues to grow, small bowel interventions are evolving that may have some effect on weight loss but focus on the treatment of obesity-related comorbidities. Read More

Annu Rev Med 2022 01 14;73:95-111. Epub 2021 Sep 14.

Division of Pulmonary, Allergy and Critical Care Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA; email:

The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges in critical care medicine, including extreme demand for intensive care unit (ICU) resources and rapidly evolving understanding of a novel disease. Up to one-third of hospitalized patients with COVID-19 experience critical illness. The most common form of organ failure in COVID-19 critical illness is acute hypoxemic respiratory failure, which clinically presents as acute respiratory distress syndrome (ARDS) in three-quarters of ICU patients. Read More