Volume 29 Issue 12, December 2023

Nature Medicine explores the latest translation and clinical research news, with results from a phase 2 clinical trial of zilebesiran from Alnylam and Roche.

Nature Medicine asks leading researchers to name their top clinical trial for 2024, from base editing and a vaccine against HIV to artificial intelligence tools for lung cancer and patient triage.

Nature Medicine asks six leading AI researchers to explain how LLM-powered chatbots are having an impact on health, from virtual nurses to detecting cancer progression.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

This year brought wins for artificial intelligence, genomics and gene editing, and breakthroughs in understanding diseases whose underpinnings have long eluded scientists. Here is our selection of critical developments that moved medicine forward in 2023.

We asked leading researchers to share new discoveries about SARS-CoV-2 and COVID-19, from how the virus spreads and the risk of long COVID to the impact of vaccines and masks.

Barriers to their training and retention threaten medical research

Physician–scientists who become parents during their long period of training need additional funding and support for lactation, childcare and healthcare, to ensure an equitable workforce.

Preclinical and initial human studies suggest that glucagon-like peptide-1 receptor agonists may be promising treatments for alcohol use disorder, but existing approved treatments should be used until safety and efficacy is demonstrated in clinical trials.

Artificial intelligence tools usually aim to maximize predictive accuracy, but personalized measures of uncertainty, using new techniques such as conformal prediction, are needed for clinical artificial intelligence to realize its potential and improve human health.

Resilience for future pandemics requires increased research and development, sustained vaccine manufacturing capabilities and global public–private collaboration.

New data show that AI could enhance imaging-based screening for pancreatic cancer; however, its evaluation must be rigorous and adhere to the same standards used for conventional screening.

Evidence supports the use of primary HPV testing to accelerate the global elimination of cervical cancer, but such recommendations must be viewed in the context of the fragile healthcare systems and complex implementation challenges in low-income and lower-middle income countries.

A phase 1 trial of an IRAK4-targeted protein degrader in patients with chronic inflammatory skin diseases hits an important milestone for the safe application of this drug class beyond oncology.

The major health consequences of violence against women present a compelling case for global prevention, detection and intervention initiatives.

A study of nearly one million people who underwent a CT scan before 22 years of age finds that the radiation from CT scans increased the risk of hematological malignancies in a dose-dependent manner. These findings highlight the continued need to justify CT scans and minimize radiation doses.

Research participants often do not represent the target population for treatment. Systematic exclusion of particular groups limits the generalizability of research and perpetuates health inequalities. The REP-EQUITY toolkit guides representative and equitable inclusion in research. Its use may promote trust between communities and research institutions and improve the applicability of research findings.

The prevalence of aneuploid cells in miscarried human embryos is higher than previously quoted. Genomic imbalances seem to be less tolerated in the embryoblast than the trophoblast, which indicates that allocation of aneuploid cells to the inner cell mass during blastocyst formation might have a detrimental effect on embryo development.

We find that people with non-suppressible human immunodeficiency virus (HIV) viremia despite antiretroviral therapy (ART) exhibit several distinguishing features. These include expanded CD4⁺ T cell clones containing HIV proviruses integrated into transcriptionally permissive regions, the presence of certain proviral defects or human leukocyte antigen (HLA)-escape mutations, enhanced survival signatures, and muted interferon and cytotoxic CD8⁺ T cell responses.

Glial cells influence brain function and disease progression. This study identifies signals that elicit hemorrhage-specific glia plasticity, including proliferation and the acquisition of neural stem cell properties. It thereby sets a foundation for aligning glia reactivity with disease progression and for attempting to use this endogenous stem cell pool for brain repair.

A validated biomarker risk score based on the expression of 34 genes improves risk stratification of patients with meningioma, including prediction of post-operative radiotherapy benefit.

The authors discuss how screening strategies, treatment approaches and precision oncology are evolving in China and outline trends and priorities in the drug development and regulatory landscape.

A deep learning model provides high accuracy in detecting pancreatic lesions in multicenter data, outperforming radiology specialists.

In a phased prospective rollout, the implementation of AI as an additional reader for mammography screening improved the real-world early detection of breast cancer compared to standard double reading involving two independent radiologists.

A modelled evaluation of screening and treatment strategies for prevention of cervical cancer in 78 low- and lower-middle-income countries provides evidence to support the World Health Organization’s recommendation of primary HPV testing for women in the general population.

A model evaluating cervical screening, triage and treatment strategies to prevent cervical cancer in women living with HIV in Tanzania provides evidence to support the World Health Organization’s recommendation of primary HPV testing starting at age 25 years with 3–5-year regular screening intervals.

A risk score based on a 34-gene signature for outcome prediction in meningioma was developed and validated in large multi-institutional cohorts and showed better performance in discriminating postoperative menignioma outcomes compared with existing meningioma classification systems.

Treatment of patients with metastatic salivary gland cancer with anti-PD-1 and anti-CTLA-4 led to encouraging clinical benefit in certain histologic subtypes, with translational analyses showing pre-existing T cell clonal expansion in responding tumors.

In a post hoc analysis of the phase 2 PRADO trial, baseline emotional distress was associated with reduced clinical responses in patients with stage III melanoma treated with neoadjuvant ipilimumab and nivolumab.

Thymic epithelial tumors are associated with increased risk of immune checkpoint inhibitor (ICI)-induced myotoxicities, and the presence of anti-acetylcholine-receptor antibodies has the potential to serve as a biomarker for ICI-induced myocarditis in patients with cancer.

Analysis of a European cohort estimated that 1–2 per 10,000 children, adolescents and young adults are expected to develop a hematological malignancy within 12 years following computed tomography examination.

The multicenter phase 3 trial of stem cell therapy for osteoarthritis (MILES) for knee pain revealed that cell therapies showed no significant difference in knee pain outcomes, compared to corticosteroid injections, 1 year following treatment.

The heterobifunctional degrader KT-474 shows target engagement and is safe to use in healthy volunteers and in patients with hidradenitis suppurativa and patients with atopic dermatitis, and it exhibits preliminary efficacy in the improvement of skin lesions and symptoms in patients.

Wireless sensing devices placed on the skin can capture a wide spectrum of acoustic and mechanical signals at several body locations simultaneously for monitoring of internal body processes such as cardiorespiratory function, gastrointestinal activity, swallowing and respiration.

Intracerebral hemorrhage triggers astrocyte proliferation and mediates neural stem cell potential via Galectin3 signaling.

A phase 1 feasibility trial shows that bilateral deep brain stimulation within the central lateral thalamus can be safely applied and is associated with improved executive control.

Analysis of hematopoietic stem cells from six individuals with sickle cell disease who had been treated with autologous gene therapy revealed positive selective pressure on cells containing mutations in genes associated with clonal hematopoiesis and hematological malignancies.

A multi-ancestry genome-wide association study of problematic alcohol use in one million individuals identified 110 risk variants and shows that multi-ancestry polygenic scores improve risk prediction compared with single-ancestry scores

A four-arm cluster-randomized trial testing the effects of a low cash incentive, a high cash incentive, a health message and a placebo on COVID-19 vaccine uptake in villages in rural Ghana demonstrated highest uptake with a low cash incentive.

Evidence that a dry-season outbreak of malaria in Dire Dawa, Ethiopia is caused by Anopheles stephensi carrying Plasmodium falciparum with diagnostic and drug resistance mutations calls for heightened vector surveillance in both urban and rural settings.

Understanding the heterogeneity of HIV infection, such as in persons with non-suppressible HIV-1 viremia despite adherence to antiretroviral treatment, is crucial to better tailor therapeutic interventions to abrogate HIV-1 persistence.

In a prespecified 3-year analysis of the KEN SHE trial, single-dose HPV vaccination was shown to be well tolerated and provided durable protection against cervical HPV infection in Kenyan women aged 15–20 years.

Genomic analysis of products of conception collected after spontaneous pregnancy loss in the first trimester reveals previously undetected chromosomal aberrations and a higher degree of mosaic chromosomal imbalances.

A meta-analysis using the burden of proof risk function identified consistent evidence supporting harmful associations between the exposure to intimate partner violence against women and childhood sexual abuse on health outcomes.

Developed through systematic review and expert consensus, the REP-EQUITY toolkit provides a seven-step guide for investigators to facilitate representative and equitable recruitment into clinical research studies.