Volume 29 Issue 7, July 2023

Nature Medicine explores the latest translational and clinical research news, with FDA approval of Seres’ orally administered pill SER-109 for the treatment of recurrent Clostridioides difficile infection.

Researchers use artificial intelligence and bioinformatics to discover new antimicrobials, while governments pilot financial incentives for pharma.

Risk-based screening approaches can reduce over-detection, while self-testing and new diagnostics find early disease.

Eighteen million children have received no routine vaccines — prioritizing them will save lives and build health infrastructure.

Climate change must be embedded in funding strategies and medical curricula, with research being best conducted in the countries most affected.

Non-communicable diseases in low- and middle-income countries can be tackled with integrated health systems interventions that consider multimorbidity, supported by patient involvement and new technologies.

Tailored community engagement led or co-led by the community can build trust with underserved communities to deliver health equity.

Unexpectedly, new data show that clonal hematopoiesis is associated with protection from Alzheimer’s disease; it is imperative that future studies unravel the complex tissue–disease contexts in which clonal hematopoiesis arises and contributes to aging-associated diseases.

A new study showing that genetic and non-genetic factors contribute to autistic traits calls for a fundamental realignment of the concepts and methods of genomics, with a critical understanding of the biosocial complexity of autism.

Artificial intelligence in combination with human expertise could be the optimal approach to improving diagnostic accuracy while maintaining a safety net in clinical imaging.

A study investigates the links between fine-scale populations and outcomes including healthcare use and disease risk in a Los Angeles biobank, unveiling crucial insights into healthcare disparities in the USA.

Escalating severity and frequency of heatwaves have outpaced the effectiveness of existing prevention and adaptation measures; there is urgency for reassessment, enhancement and implementation of strategies to mitigate health impacts in dealing with this global health challenge.

We show that integrating multi-omic approaches with ultra-rapid whole-genome sequencing improves diagnosis in critically ill infants and children with rare diseases and can be successfully delivered on a national scale.

We investigated the presence of genetic variants for 105 genes previously associated with premature ovarian insufficiency (POI) in over 100,000 women. We found that predicted damaging variants in these genes were commonly found in the heterozygous state in women that had menopause within the normal age range. This suggests that monogenic causes of POI are rare, and that POI is more likely to be a polygenic disorder.

This study reveals that the production of cobalamin and succinyl-CoA is increased in the anal microbiome of patients with precancerous anal lesions. Testing for these two metabolites significantly improves diagnostic accuracy over standard cytology screening, which suggests potential for enhanced screening strategies for anal cancer.

Genome-wide polygenic scores quantify inherited risk by integrating information from many common DNA variants and hold considerable promise for enabling personalized medicine. By integrating information on coronary artery disease (CAD) and CAD-related risk traits from genetic datasets that were larger and more diverse than those used in the past, we developed an improved multi-ancestry polygenic predictor for CAD.

As the proportion of older adults increases globally, digital health innovations, particularly wearables, could transform the future of healthy aging.

This Review outlines three ‘grand challenges’ to protect and promote health in the face of climate change, and discusses the role of the health community in driving change within and beyond the health sector.

Adverse childhood experiences can negatively impact lifelong health; this Review discusses the underlying mechanisms and potential solutions, advocating for multisectoral interventions and implementation research.

Multimorbidity is increasing globally, and addressing it requires a shift in the prevailing clinical, educational and scientific thinking. This Review discusses emerging mechanisms, research challenges and the implications for patients and healthcare systems.

Clonal hematopoiesis of indeterminate potential (CHIP) was found to be associated with a protective effect from Alzheimer’s disease (AD) in large population-based cohorts.

Analyses of data from more than 200,000 individuals identify phenotypic features associated to carrying variants in autism-associated genes, in individuals with and without a diagnosis of autism.

A report from the Australian Acute Care Genomics programme shows that the integration of rapid whole-genome sequencing and multi-omic analyses informs diagnoses and treatment decisions in a prospective cohort of 290 critically ill infants and children.

Using exome sequencing data from 104,733 postmenopausal women in the UK Biobank, an analysis of 105 gene variants previously reported as associated with premature ovarian insufficiency reveals that most cases are not monogenic.

In children with relapsed or refractory B cell acute lymphoblastic leukemia and in complete remission after CD19 CAR-T cell therapy, long-lived CAR-T cells express a persistence gene signature that is also present in persistent CD19 CAR-T cells from adults with chronic lymphocytic leukemia.

Prophylactic subcutaneous administration of anakinra, an IL-1 receptor inhibitor, reduced severe immune effector cell-associated neurotoxicity syndrome incidence in patients with relapsed or refractory large B-cell and mantle cell lymphoma treated with anti-CD19 chimeric antigen receptor (CAR) T cells.

Prospective assessment of a T-cell-inflamed gene signature and tumor mutational burden is feasible in patients with non-small cell lung cancer randomized to receive various anti-PD-1-based treatment combinations, with an encouraging objective response rate for first-line pembrolizumab + lenvatinib in one biomarker-defined group.

In a phase 2 trial of patients with untreated, recurrent and progressive brain metastases treated with an anti-programmed cell death protein 1 inhibitor, the overall intracranial benefit rate was 42.1%, which met the prespecified primary endpoint.

Two products of the anal microbiome improve the specificity and sensitivity of diagnosing high-grade precursor lesions to anal cancer over cytology.

Examining the interplay of environmental exposure with the airway microbiome provides insights for possible intervention in lung health.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

Cross-sectional and longitudinal analyses of tau pathology in preclinical Alzheimer’s disease reveal that tau tangles accumulate as a function of amyloid-β burden only in individuals positive for an astrocyte reactivity biomarker.

In a phase 2, randomized clinical trial in patients with severe hypertriglyceridemia, pegozafermin, a long-acting analog of human fibroblast growth factor 21, was safe and met the primary endpoint of the trial for reducing serum triglyceride levels.

A polygenic risk score for coronary artery disease developed using data from individuals of five different ancestries has increased accuracy across diverse populations.

A machine learning algorithm, developed to detect occlusion myocardial infarction with no-ST elevation from electrocardiogram, outperforms clinicians in diagnostic assessments.

A collaboration system helps to integrate decisions between human experts and AI to optimize screening and triaging and to reduce clinicians’ workload.

A risk score developed using biological, psychological and social factor data from the UK Biobank can predict different pain conditions, the risk of chronic pain spreading across body sites and the prognosis of chronic pain up to 9 years later.

A genome-wide meta-analysis of data from six US and European cohorts involving 1.3 million individuals identifies 243 genetic variants associated with risk and pathophysiology of depression, which is used to develop polygenic risk scores for the prediction of depression recurrence and comorbid psychiatric disorders.

Analyses using genetic data and electronic medical records as part of the ATLAS Community Health Initiative revealed differences in disease risk and healthcare utilization among ancestrally diverse groups in the Los Angeles region.

This ecological analysis using the Eurostat database estimated that summer 2022, the hottest summer on record, was associated with over 61,000 heat-related deaths across 35 countries in Europe, with the highest mortality rates in countries near the Mediterranean Sea.

A meta-analysis of individual-level patient data from 66 clinical studies supports the utility of glomerular filtration rate as a surrogate endpoint in clinical trials for chronic kidney disease, with potential to enable detection of events earlier in the disease course.