Volume 29 Issue 10, October 2023

Nature Medicine explores the latest translation and clinical research news, with a phase 3 trial from Merck and Moderna testing mRNA-4157 combined with pembrolizumab in melanoma.

Nature Medicine explores the latest translational and clinical research news, with early results from a phase 3 clinical trial of the GLP-1 receptor agonist semaglutide.

Systematic reviews and meta-analyses are used by clinicians and policymakers to synthesize medical evidence, but they can amplify falsified or poor-quality clinical trial data. In this era of contested evidence, new approaches are needed.

The reignited Cancer Moonshot must support science that will tackle health and economic impacts of cancer and promote health equity in low- and middle-income countries.

Chatbots powered by artificial intelligence used in patient care are regulated as medical devices, but their unreliability precludes approval as such.

The UN SDGs will only improve human health if they are accompanied by systemic change that addresses global power imbalances.

A breakthrough in drug discovery for glioblastoma requires serial collection of tissue from the central nervous system via window of opportunity trials

Mounting evidence, including the recent (and unprecedented) phase 2 data on retatrutide, supports a role for incretin hormone agonists in treating obesity. But with great power comes great responsibility.

As the search for new and better treatments for Alzheimer’s disease continues, a phase 1 proof-of-concept study evaluating senolytic therapy breaks new ground.

Researchers have developed a screening tool for autism that uses computer vision and machine learning to analyze autism-related behaviors — but greater reliability and robust validation will be needed if such tools are to be used in primary care settings.

A novel AI-based decision support system for insulin titration in type 2 diabetes reveals important considerations surrounding the feasibility of clinical implementation.

Despite an urgent need, approved and clinically usable biomarkers for non-alcoholic steatohepatitis (NASH) remain elusive — but a new study moves the field closer to this goal.

Whole-genome sequencing of Clostridioides difficile from a densely sampled intensive care unit (ICU) population showed that many of these patients harbor toxigenic C. difficile. This carriage did not lead to high levels of cross-transmission but was associated with a greatly increased risk of developing clinically overt C. difficile infection.

Aberrant immune responses to the intestinal microbiome have emerged as major contributors to chronic intestinal inflammation, but the microbial species involved in inflammatory bowel diseases remain unknown. Our study identified dietary and commensal yeasts of the gut that drive the expansion of some cross-reactive CD4⁺ type 1 helper T cells with cytotoxic effector functions, which potentially contributes to immunopathology in patients with Crohn’s disease.

Clinical and population-based cohorts revealed an interaction between the inherited PNPLA3 p.I148M variant and female sex in determining liver disease. Transcriptomic and functional studies showed that the mechanism encompasses ERα-dependent upregulation of PNPLA3 in hepatocytes, highlighting a target for precision medicine therapeutics in cisgender women.

Recent years have seen major advances in heart failure treatment, but gaps in implementation and disparities in care remain; this Review outlines the current state of the field.

A systematic review of evidence, across the key pillars of prevention, diagnosis, treatment and prognosis, outlines milestones that need to be met to enable the broad clinical implementation of precision medicine in diabetes care.

In a retrospective analysis of patients with Lynch syndrome and primary cancers treated with immune checkpoint inhibitors, 12% developed subsequent malignancies, suggesting that this treatment may not eliminate risk in individuals predisposed to mismatch repair-deficient cancers, and ongoing surveillance is warranted.

In the phase 3 STAR trial, subretinal administration of the AAV2-based gene therapy timrepigene emparvovec in patients with choroideremia did not lead to a significant difference in the primary endpoint of 15-letter Early Treatment Diabetic Retinopathy Study (ETDRS) improvement in visual acuity from baseline compared to untreated controls.

Results from the phase 3 placebo-controlled MAPP2 trial show that MDMA-assisted therapy reduces post-traumatic stress disorder (PTSD) symptoms and functional impairment in a diverse population with moderate to severe PTSD.

The first feasibility study of orally delivered senolytic therapy in Alzheimer’s disease reports favorable safety data and penetrance of dasatinib into the brain with a modest impact on Alzheimer’s and aging biomarkers.

In a prospective study, an autism screening app administered using a tablet computer to young children showed high diagnostic accuracy and may facilitate a scalable approach to autism screening.

Longitudinal proteomic profiling of over 1,800 patients revealed two distinct profiles of blood biomarkers measured on admission to hospital for COVID-19, which predict cognitive deficits 6 and 12 months later.

An analysis of viral genomes and epidemiological data from the 2022 mpox outbreak in Portugal sheds light on the heterogeneity of early transmission events, with national and international linkages.

New treatments are essential for methicillin-susceptible Staphylococcus aureus bacteremia, but progress is slow. In this phase III–IV trial, cloxacillin plus fosfomycin failed to show superiority over cloxacillin alone, underscoring the challenges to improving patient outcomes.

A low rate of Clostridioides difficile transmission within an intensive care unit supports the effectiveness of prevention practices and highlights the greater risk to carriers of toxigenic C. difficile.

Reactivation of latent SIV with an IAP antagonist, coupled with immunotherapeutic approaches, reduced replication-competent SIV in lymph node CD4⁺ T cells in rhesus macaques. Further exploration targeting these pathways to reduce the HIV viral reservoir is warranted.

In people with HIV-1 undergoing antiretroviral treatment interruption, lefitolimod combined with broadly neutralizing antibodies (bNAbs) did not delay viral rebound beyond that achieved with bNAbs alone, raising the question of how to optimize combination immunotherapy to control HIV-1.

In the first stage of the BR.36 adaptive trial in patients with non-small cell lung cancer receiving anti-PD1 immunnotherapy, the primary endpoint of concordance between circulating tumor DNA (ctDNA) molecular response and RECIST response was met. The results will inform the second, ctDNA-directed stage.

In the first-in-human trial of elranatamab, patients with refractory or relapsed multiple myeloma who received the bispecific antibody against BCMA and CD3 experienced no dose-limiting toxicities during dose escalation, and the agent showed promising clinical efficacy.

The combination of a bispecific antibody against EGFR and MET with a tyrosine kinase inhibitor (TKI) in patients with TKI-relapsed, chemotherapy-naive, EGFR-mutated advanced NSCLC is safe and shows preliminary efficacy.

In this compassionate use study, treatment of adult patients with H3K27M-mutant diffuse midline glioma with a long peptide vaccine targeting H3K27M led to vaccine-induced peripheral T cell immune responses and encouraging clinical efficacy in the majority of patients, including a durable complete response.

In the ALYCANTE trial, second-line treatment with axicabtagene ciloleucel, a CD19-targeting CAR T-cell therapy, resulted in high response rates and durable remissions in patients with high-risk large B-cell lymphoma deemed ineligible for autologous stem cell transplantation.

In patients with Crohn’s disease, CD4⁺ T cells with cytotoxic T_H1 cell-like effector functions reactive against dietary and commensal yeasts are increased in blood and inflamed tissue compared with patients with ulcerative colitis and healthy controls.

In the LUMINA-1 trial for fibrodysplasia ossificans progressiva, garetosmab, an activin A monoclonal antibody, did not lead to significant changes in heterotopic ossification lesion activity in pre-existing lesions in period 1. Garetosmab prevented the formation of new lesions in both periods 1 and 2.

In patients with acute heart failure, personalized dosing of a diuretic led to treatment intensification in the majority of patients and improved natriuresis, but had no effects on time to all-cause mortality or heart failure rehospitalization.

A reinforcement learning algorithm achieved superior insulin titration optimization versus other deep learning models and standard clinical methods in a prospective cohort and in a proof-of-concept feasibility trial.

Analysis using a combination of molecular and genetic epidemiological approaches reveals an interaction between female sex and the genetic variant PNPLA3 p.I148M that might explain why some women have increased susceptibility to fatty liver disease after onset of menopause.

The NIMBLE biomarker qualification project evaluated the diagnostic performance of five blood-based biomarkers in a cohort of individuals with non-alcoholic fatty liver disease and showed good discriminative performance over commonly used laboratory tests in detecting various stages of non-alcoholic steatohepatitis progression.