Volume 30 Issue 9, September 2024

With the first CRISPR–Cas9 gene therapy now approved, scientists are turning to newer editing technologies to produce safer, faster and better treatments for genetic diseases.

Student doctors push for the health impacts of extreme weather to be taught in medical schools, as the carbon emissions from healthcare come under greater scrutiny.

Transforming the fragmented silos of medicine into a wheel of collaboration holds the key to tackling complex health challenges for generations to come.

The European Association for the Study of Obesity presents a new framework for the diagnosis, staging and management of obesity in adults to better align with the concept of obesity as an adiposity-based chronic disease.

The World Health Organization framework for tracking SARS-CoV-2 variants has been updated to reflect the continued evolution of the virus; this framework could be adapted for other emerging respiratory diseases with epidemic and pandemic potential.

The lay summary of trial results to be provided to participants should be written in plain language, use infographics and be concise — something that currently is almost never achieved.

In a new study, neoadjuvant immunotherapy led to major pathological responses in patients with locally advanced colon cancer harboring mismatch repair deficiency — and emerging evidence suggests that organ-sparing approaches may also be feasible.

Although large language models (LLMs) show promise in controlled settings, a study now exposes their limitations in real-world clinical applications and points the way towards robust evaluation and benchmarking before clinical use.

A study uses '-omics' and artificial intelligence to derive a metric that distinguishes normal immunity from its perturbation — and reveals that healthy immune systems are less alike than anticipated.

Infections account for the highest number of non-relapse-related deaths after CAR T cell therapy, underscoring the necessity for clinical risk-mitigating strategies and a deeper understanding of CAR T cell-related cytopenia.

In a large human population study of proteomic aging, we developed a proteomics-based age clock for UK Biobank participants and validated its accuracy in the China Kadoorie Biobank and FinnGen. Proteomic aging is associated with mortality, risk of 18 chronic diseases and numerous age-related traits, including cognitive function.

In an observational cohort study of adults living with obesity and diabetes, we found that the primary incidence of congestive heart failure was lower in patients treated with bariatric metabolic surgery than in those on first-generation GLP-1 receptor agonists, an effect that was not explained by greater weight loss in the group that received bariatric metabolic surgery.

Measuring between 5 and 20 proteins in the blood predicts the future risk of developing a diverse range of 52 diseases across clinical specialties. These protein signatures perform better than standard risk factors and blood tests used in clinical practice for risk prediction. Examples of well-predicted diseases include multiple myeloma and idiopathic pulmonary fibrosis.

We present the Brain Cell Atlas, integrating single-cell transcriptomes of 26 million cells from 70 human and 103 mouse studies, covering 14 major brain regions. This atlas takes advantage of the integration of big data, enabling the discovery of putative neural progenitors in adults and microglial regional variations.

This Perspective calls for inclusion of patients with MASLD and measurement of liver outcomes in cardio–kidney–metabolic trials, when data suggest mechanistically plausible benefits and clinical safety—and outlines considerations for trial design and regulatory approval.

Tackling antimicrobial resistance will require a sustainable research and development ecosystem for antibiotic development, alongside strategies for responsible use and global access.

A proteomic aging clock, developed using data from the UK Biobank and validated using data from the China Kadoorie Biobank and FinnGen, predicts the incidence of 18 major chronic diseases, as well as multimorbidity and all-cause mortality.

A multimodal analysis of patients with 22 different immune-mediated monogenic diseases versus matched healthy controls leads to the development of the immune health metric, which could be implemented broadly to predict responses to aging, vaccination and other immune perturbations.

In a phase 1/2 trial, the recombinant interleukin-1 receptor antagonist anankira was safe and associated with clinically meaningful improvements in neurobehavioral and quality-of-life outcomes in patients with Sanfilippo syndrome.

A combined-ancestry GWAS of diabetic retinopathy, comprising 68,169 cases and 129,188 controls, revealed nine previously unreported loci associated with the condition, including an evolutionarily adaptive genetic variant alongside a potential functional mechanism that influences racial disparities in diabetes complications among individuals of non-Hispanic African ancestry.

Proteomic prediction models developed using a large-scale dataset from the UK Biobank Pharma Proteomics Project were superior to clinical models for assessing the 10-year risk of 67 diseases across different types of pathology, including multiple myeloma, motor neuron disease, pulmonary fibrosis, celiac disease and dilated cardiomyopathy.

An analysis of three multi-cancer cohorts shows that the detection of ctDNA using liquid biopsies has the potential to improve the risk prediction of cancer-associated venous thromboembolism.

In an exploratory analysis of the KEYNOTE-361 phase 3 trial that tested immunotherapy and chemotherapy in advanced urothelial carcinoma, different early circulating tumor DNA (ctDNA) dynamics were observed between the two treatments, and ctDNA levels were associated with response to pembrolizumab but not to chemotherapy.

In a phase 1b/2a trial, the combination of the oral PI3K inhibitor duvelisib and romidepsin had limited toxicity and exhibited encouraging clinical activity in patients with relapsed or refractory T cell lymphoma, suggesting an approach whereby PI3K inhibitors can be safely used in this patient population.

In a Bayesian adaptive randomized trial comparing various metronomic chemotherapy regimens versus conventional chemotherapy plus anti-PD-1 in women with HER2-negative breast cancer, a metronomic chemotherapy-based regimen appears to be clinically effective, with evidence that on-treatment immune changes may be trackable for assessing response.

In this non-comparative trial, patients with BRAF^V600-mutant resectable melanoma received either pembrolizumab alone, a sequential combination of pembrolizumab, dabrafenib and trametinib, or a concurrent combination thereof, showing encouraging clinical response rates in the concurrent therapy arm and awaiting longer follow-up.

In a randomized phase 3 trial, neoadjuvant anti-PD-1 plus either paclitaxel and cisplatin or nab-paclitaxel and cisplatin elicited a significantly superior pathological complete response rate versus neoadjuvant paclitaxel and cisplatin alone in patients with resectable locally advanced esophageal squamous cell carcinoma.

In an ongoing phase 1 trial, the combination of two new immunotherapies targeting CTLA-4 and PD-1 was overall well tolerated and elicited encouraging clinical responses in patients with relapsed/refractory microsatellite stable colorectal cancer, a tumor type typically unresponsive to immune checkpoint blockade.

In this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

In a randomized phase 1 trial, the addition of a live Clostridium species-containing product to a tyrosine kinase inhibitor and anti-programmed cell death protein 1 treatment combination did not increase bacterial abundance of Bifidobacterium spp. but enhanced clinical responses in participants with metastatic renal cell carcinoma.

Preliminary findings in seven patients with mismatch repair-proficient metastatic colorectal cancer who were treated in the context of a phase 2 trial show that adoptive transfer of autologous peripheral blood T lymphocytes that were retrovirally transduced with personalized neoantigen-reactive T cell receptors can be safe and induce early clinical responses.

A randomized controlled trial performed in a screen-and-treat program in Zambia found that a portable, battery-operated thermal ablation device was not inferior to cryotherapy and electrosurgical excision in cervical precancer treatment.

In a phase 2 randomized control trial, intermittent senolytic therapy administered to postmenopausal women did not result in a reduction in the bone resorption marker, serum CTx, compared to control at 20 weeks.

Using a curated dataset of 2,400 cases and a framework to simulate a realistic clinical setting, current large language models are shown to incur substantial pitfalls when used for autonomous clinical decision-making.

In an interim analysis, an artificial intelligence model was nearly four times more efficient in terms of cancers detected per number of magnetic resonance imaging tests, compared to traditional breast density measures used in a previous clinical trial.

A first-in-patient trial of UB-312, an active immunotherapeutic for Parkinson’s disease, was well tolerated and elicited antibodies that engage misfolded α-synuclein.

In an analysis of five large randomized clinical trials testing established therapies for cardiovascular disease, individuals with clonal hematopoiesis had an increased risk for first but not recurrent myocardial infarction as compared to individuals without clonal hematopoiesis, and did not show increased benefit from any of the therapies tested.

In a cohort of 6,785 participants from the All of Us Research Program whose sleep was monitored by a Fitbit over a median of 4.5 years, sleep duration, stages and irregularity were associated with the incidence of obesity and a number of cardiovascular and psychological disorders.

A phase 2 randomized controlled trial of ustekinumab in 72 adolescents with recent-onset type 1 diabetes showed that treatment was well tolerated and β-cell function was 49% higher in the intervention group compared to the placebo arm after 12 months.

In a systematic review and meta-analysis of nonrelapse mortality (NRM) following CAR T cell treatment in 7,604 patients with lymphoma and myeloma, almost half of cases were atrributable to infections and NRM estimates varied across both tumor types and CAR T cell products

A single-cell transcriptomic study from the Human Cell Atlas integrating over 11 million brain cells from 70 studies uncovers differences across human brain regions and identifies rare progenitor and microglia subtypes.