Volume 28 Issue 12, December 2022

Nature Medicine explores the latest translational and clinical research news, with an analysis of Intellia and Regeneron’s gene-editing treatment, which reduced levels of transthyretin in patients.

Nature Medicine explores the latest translational and clinical research news, with a clinical trial of an intranasal ChAdOx1 vaccine.

Up-and-coming researchers who are blazing a trail in their respective fields share what they are most excited about and where their research going in the next 5 years.

Nature Medicine asks leading researchers to name their top clinical trial for 2023, from cervical and prostate cancer screening to new drugs for Parkinson’s disease and Alzheimer’s disease.

This year saw breakthroughs in several fields, spurred by research in basic science and technology. Here is our selection of critical developments that moved medicine forward in 2022.

Gender-affirming care for transgender and gender diverse people should be inclusive, community led and evidence informed to support mental health and wellbeing.

Authors of biomedical research should provide clear and accurate information to society, whilst working to combat misinformation and disinformation.

Healthy eating habits require effective collaborations among stakeholders — such as researchers and food retailers — to be impactful and sustainable.

A variant of the IL7 gene predicts the toxicity of checkpoint inhibitors in patients with cancer, via a mechanism shared with autoimmune diseases — which could inform biomarker and treatment strategies in both of these contexts.

Osteoarthritis is highly heterogeneous, so effective therapies will need to target clearly defined molecular endotypes, restore mechanical joint function and reduce pain; thus, a ‘one-size-fits-all’ approach is unlikely to succeed.

Embryo culture during assisted reproduction treatment may be associated with altered risks for health and aging across the lifespan of the offspring.

To enable large-scale screening for left ventricular dysfunction — a serious and under-detected cardiac disease — we applied artificial intelligence to electrocardiograms recorded by patients using their own Apple watches in a prospective, digital, remote study. We found that patients engaged with the system and that the watch electrocardiograms effectively screened for the disease.

Subgroup analysis of the EMPEROR-Preserved clinical trial of the glucose-lowering drug empagliflozin in chronic heart failure with left ventricular ejection fraction (LVEF) >40% found improved clinical outcomes in the cohort of patients with LVEF ≥50%. This is, to our knowledge, the first time a drug therapy has been unequivocally demonstrated to benefit this patient population.

Inhaled particulates from environmental pollutants accumulate in macrophages in lung-associated lymph nodes over years, compromising immune surveillance via direct effects on immune cell function and lymphoid architecture. These findings reveal the importance of improved air quality to preserve immune health against current and emerging pathogens.

Vigorous intermittent lifestyle physical activity (VILPA) refers to brief bouts of strenuous movement performed as part of daily living, such as walking uphill or running for a bus. We find that as little as 3–4 minutes of VILPA per day is associated with substantially reduced mortality risk compared to no VILPA.

This Perspective outlines how cell atlases can provide the missing links between genes, diseases and therapies, with advances already being made in several fields, including COVID-19 and cancer.

In this proof-of-concept prospective study, single-lead electrocardiograms obtained by smartwatches were able to identify individuals with left ventricular dysfunction, potentially serving as an early warning system for heart failure.

A prespecified analysis of the DELIVER clinical trial shows that the sodium/glucose cotransporter 2 inhibitor dapagliflozin benefits patients categorized as having heart failure with improved ejection fraction, a class of patients at high risk of cardiac events but for which limited treatment data are available.

Analysis of the results of a large clinical trial, EMPEROR-Preserved, shows that the SGLT2 inhibitor empagliflozin improves outcomes for heart failure patients with either mid-range (41–49%) or preserved (≥50%) ejection fraction, supporting the use of this drug for both categories of patients.

Using data from wearable activity monitors, this study shows that short bursts of physical activity that are done as part of daily life activities and that are only 1 or 2 minutes in length are associated with lower mortality, similar to the effects of regular exercise.

In a randomized control trial, individuals who received dietitian-led counseling in the supermarket, together with web-based tools, had improved dietary quality in comparison to a control group, as assessed by adherence to the heart-healthy DASH diet plan.

Identification and characterization of variants in HTR2C in people with severe obesity, reveals a role for serotonin 2C receptor in regulation of appetite, weight and behavior.

Cerebrospinal fluid measures of isoform-specific tau species from the microtubule-binding region serve as the first fluid biomarkers of primary tauopathy.

Longitudinal study of plasma biomarkers, in two independent cohorts, highlighted only p-tau217 as a surrogate marker of disease progression in early Alzheimer’s disease, supporting the development of new disease-modifying treatments.

According to 2020 estimates from 185 countries, Asia and Africa have the most maternal orphans due to cancer, with breast and cervical cancers responsible for almost half of maternal cancers.

In patients with metastatic triple-negative breast cancer, atezolizumab combined with immunogenic, anthracycline-based metronomic chemotherapy improves progression-free survival, including in patients with PD-L1^negative disease.

A genome-wide association study in large cohorts of patients with different types of cancer treated with immune checkpoint inhibitors identifies genetic variants associated with immune-related adverse events.

Genetic analyses in a cohort of patients with melanoma receiving immunotherapy reveal that variants in IL7 are associated with immune-related adverse events and highlight the role of B cells in mediating toxicity.

A CD8-specific, one-armed antibody positron emission tomography tracer enables the visualization of the immune response in patients with solid tumors before and after starting immunotherapy.

Vaccines that elicit HIV-specific T-cell responses did not prevent viral rebound in people living with HIV upon antiretroviral treatment (ART) interruption, but associated with longer time off ART in some trial participants, suggesting their immunogenicity may benefit future cure approaches.

Carbon-containing particulates accumulate with age in a subset of macrophages in human lung-associated lymph nodes, decrease macrophage phagocytic capacity and turnover and disrupt lymphoid tissue structure, potentially compromising adaptive immune responses.

The mechanism of action of LNA043—a novel disease-modifying osteoarthritis treatment candidate—is characterized in preclinical studies and through transcriptomic profiling of cartilage from patients with osteoarthritis in a phase 1 trial.

Analyses of whole-genome sequencing data in children and validation in mouse models show that offspring born from blastocyst-stage embryo transfer have shorter leukocyte telomere lengths.