Volume 29 Issue 1, January 2023

Nature Medicine explores the latest translational and clinical research news, with news that sotatercept met its primary endpoint in the STELLAR trial.

Nature Medicine explores the latest translational and clinical research news, with a clinical trial of a tRNA synthetase inhibitor for tuberculosis.

A desire for better work conditions and real-world impact are behind the movement, which may hinder academic clinical trials while leading to beneficial collaborations.

Technological innovation and changes to regulation are disrupting the hearing health sector, with implications for data privacy, product safety and accessibility, and provide challenges and opportunities for equitable hearing health.

Integrating microbial sequencing data into electronic health records, while presenting privacy concerns, will improve patient care and population health and will expand the secondary uses of such data.

Artificial intelligence algorithms have had mixed success in health, in part because regulation prevents them from evolving at the necessary rate.

A phase 1 trial using an allogeneic stem-cell-based therapy in people with progressive multiple sclerosis (MS) shows the feasibility and tolerability of the approach; rigorous evaluation of this and other regenerative strategies for MS is now urgently needed.

As another clinical trial of a mitochondria-targeting cancer therapy faces failure, it calls for a thorough re-evaluation of the strategy; the time has come to go from the bedside back to the bench.

A clinical trial shows the feasibility of a noninvasive imaging approach to diagnose a surgically amenable subtype of primary aldosteronism — a common and often poorly managed form of hypertension.

Automated insulin delivery systems that are already used in type 1 diabetes show promise for patients with type 2 diabetes, and are poised to have a substantial effect on public health.

Prospective, longitudinal clinical studies incorporating high-throughput, single-cell analyses could identify which bacterial antigens to include in TB vaccines — and which to avoid.

Clinical trials in neurological diseases often involve subjective, qualitative endpoints, such ‘by eye’ observations of movement. We developed an artificial intelligence–based method to analyze natural daily behavior data from people with Duchenne muscular dystrophy, using machine-learning algorithms to accurately predict their personal disease trajectories better than conventional clinical assessments.

The large, ongoing CIRCULATE-Japan trial is investigating the role of circulating tumor DNA (ctDNA)-based molecular residual disease testing in patients with resectable colorectal cancer after radical surgery. An interim analysis of GALAXY, a prospective, observational arm of CIRCULATE-Japan, establishes ctDNA as a prognostic and predictive biomarker.

The cause of pregnancy loss or perinatal death often remains unexplained, even following a standard autopsy. Comprehensive genomic investigation of pregnancy loss or perinatal death identifies a cause in over 50% of cases, particularly where congenital abnormalities are present. Causes of stillbirths without congenital abnormalities remain difficult to identify.

By performing a large-scale biobank-based genome-wide association study, we identified a strong link between the underlying risk of cardiometabolic disease and patterns of lifelong medication use in hyperlipidemia, hypertension and type 2 diabetes. We discover hundreds of genetic predictors of medication use behavior and show medication-use-enhanced applications for polygenic prediction in cardiometabolic diseases.

We demonstrate the power of a data-informed medicines-based approach in discovering the indirect effect of the COVID-19 pandemic on cardiovascular events using 1.32 billion records of dispensed medications in England, Scotland and Wales. We estimate that interruption of preventive care could result in more than 13,000 extra cardiovascular events.

A machine learning algorithm identifies four reproducible clinical subphenotypes of long COVID from the electronic health records of patients with post-acute sequelae of SARS-CoV-2 infection within 30–180 days of infection; these patterns have implications for the treatment and management of long COVID.

Technological advances are transforming evidence generation in medicine; for these advances to impact public health, the clinical trial landscape must evolve and adapt to keep pace.

Moving away from the traditional ‘tumor-centric’ view, the authors explore how systemic biology, as well as aging, co-morbidities and co-medications, all interact and influence cancer development and progression.

Phase 1 trial results reveal that intrathecal transplantation of human fetal neural precursor cells in patients with progressive multiple sclerosis is feasible, safe and tolerable.

Full-body movements captured using a multisensor body suit predict the clinical trajectory of patients with Friedreichʼs ataxia, providing digital biomarkers of disease progression.

A digital biomarker derived from a multisensor bodysuit that monitors whole-body movement while individuals perform everyday activities can predict disease progression in Duchenne muscular dystrophy.

In a phase 1 dose-escalation trial in patients with nine different types of solid tumors, MAGE-A4-specific T cells had an acceptable safety profile and exhibited an encouraging overall response rate in patients with synovial sarcoma.

A mitochondrial complex I inhibitor exhibited dose-limiting toxicities, including neurotoxicity, in patients with acute myeloid leukemia and solid tumors, warranting further studies to evaluate the mechanism linking oxidative phosphorylation inhibition and neurotoxicity.

In the observational GALAXY arm of the CIRCULATE-Japan study, among 1,049 patients with stage II–IV colorectal cancer, those with presence of circulating tumor DNA (ctDNA) after tumor resection have a high recurrence risk and are likely to benefit from adjuvant chemotherapy.

Federated learning improves prediction of the histological response to neoadjuvant chemotherapy in patients with triple-negative breast cancer, demonstrating the feasibility of this approach for analysis of multicenter cohorts of patients with rare diseases.

Variation in antibody levels elicited by the COVID-19 vaccine ChAdOx1 nCov-19 is linked to specific major histocompatibility complex class II alleles, providing insight into the breadth of immune response among vaccinated individuals.

Integrative genomic and transcriptomic analyses reveal molecular events defining Richter transformation from CLL, and highlight the potential of cell-free DNA for early detection.

Pharmacotyping analyses of large cohorts of pediatric acute lymphoblastic leukemia identify correlations between drug sensitivities and clinical outcomes across different genomic subtypes.

In a new study including 200 families who experienced perinatal death, adding genomic analyses to standard autopsies improved the identification of underlying pathogenic causes and informed genetic counseling.

Comparison of non-invasive [¹¹C]metomidate PET-CT with adrenal vein sampling for predicting biochemical remission of primary aldosteronism showed non-superiority, suggesting that the non-invasive method is suitable for the diagnosis of unilateral primary aldosteronism.

In a randomized, crossover trial in adults with type 2 diabetes, fully closed-loop insulin delivery increased time in target glucose range compared with standard insulin therapy, without increasing hypoglycemia.

A new analysis of large biobanks uncovers genetic variants associated with longitudinal changes in medication for cardiometabolic diseases and presents polygenic scores of medication-use behavior.

Analysis of 1.32 billion records of medication data from England, Scotland and Wales reveals that the COVID-19 pandemic led to substantial declines in dispensing of antihypertensive and lipid-lowering medications, leading to increased risks for future cardiovascular disease.

Machine learning applied to electronic health records in two US cohorts from the RECOVER initiative identified four Long-COVID subphenotypes that differ in the involvement of organ systems, previous SARS-CoV-2 infection severity and underlying conditions.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Bivalent vaccines elicit broad immune responses that neutralize ancestral SARS-CoV-2 and variants of concern and offer a customizable approach to protect from COVID-19 as new virus variants emerge.

Analysis of peripheral mycobacteria-reactive CD4⁺ T cell receptor sequences from individuals infected with Mycobacterium tuberculosis shows a high degree of overlap between progressors and controllers, but points to some distinct clonotypes that are enriched in either group.

Historic smallpox vaccination and monkeypox virus (MPXV) infection elicit MPXV-neutralizing antibodies, but MPXV-neutralizing antibodies are less frequent and of lower magnitude after vaccination with MVA-BN—the vaccine approved and in use for protection against MPXV and smallpox.