Volume 29 Issue 11, November 2023

Nature Medicine explores the latest translation and clinical research news, with results from a clinical trial of Novartis' discontinued gene therapy to restore fetal hemoglobin.

Nature Medicine explores the latest translation and clinical research news, with two separate groups announcing that genetically modified pig kidneys are functional in brain-dead human hosts.

Billions of dollars are pouring into longevity biotechs, but measuring success is challenging, given how little is known about the biology of aging.

Artificial intelligence chatbots based on large language models can pass medical exams but their diagnoses are often inaccurate.

Not involving communities throughout the research process may be attributable to prejudice and a failure to recognize privilege. The result is a loss for all involved.

External comparator arms should be used when investigating novel therapies for gastrointestinal stromal tumor and other rare tumors to facilitate drug testing and regulatory approvals.

AstraZeneca has introduced digital health solutions into clinical trials, demonstrating improved patient experience, accelerated timelines and reduced costs.

Use of telepsychiatry increased during the COVID-19 pandemic, resulting in greater access and the potential for improved care, although barriers to wider adoption remain.

The introduction of publicly funded not-for-profit institutional review boards would realign incentives to promote research participants’ interests and improve accountability.

We asked the winners of the Nature Award for Inclusive Health Research to share their key lessons for conducting medical research in partnership with under-represented communities.

Two modelling studies offer compelling evidence that less-than-perfect adherence to HIV pre-exposure prophylaxis can still provide reasonable protection for cisgender women — providing optimism for a more person-centered approach and lower discontinuation rates.

The response to neoadjuvant treatment can be used to stratify individuals with muscle-invasive bladder cancer according to their risk of progression, enabling bladder-sparing approaches for some — and heralding a shift from the existing one-size-fits-all approach.

A new approach that combines CAR T cells with serial mRNA vaccine injections facilitates robust anti-neoplastic activity in patients with genitourinary cancers, which will pave the way for a promising new targeted treatment strategy.

Epidural electrical stimulation of the spinal cord alleviated freezing-of-gait and other postural impairments in a patient with Parkinson’s disease, potentially addressing an unmet need and offering an exciting new avenue for therapy.

A spatially coupled, individual-based simulation of malaria in Rwanda was used to evaluate changes in drug policy in response to artemisinin-resistant Plasmodium falciparum. Our findings suggest that the deployment of multiple first-line therapies has the potential to reduce treatment failures and slow the fixation of resistant alleles in populations.

By analyzing human samples and multiple mouse models of Huntington’s disease, we found that complement proteins and microglia mediate early and selective loss of corticostriatal synapses. Strategies that block this process can reduce synaptic loss, increase excitatory input to the striatum and prevent the development of cognitive deficits in mice.

The induction of neutralizing antibodies is the main goal of an HIV-1 vaccine, although data on the longevity of such antibodies is lacking. By tracking neutralizing antibodies in a large cohort of individuals infected with HIV-1 who had varying viral loads, we show that the HIV-1 neutralization response can last for several years even at low antigen levels.

This Review explores how research coproduction with Indigenous peoples is evolving; it discusses the challenges and complexities and makes recommendations for researchers wishing to pursue coproduction with Indigenous peoples in responsive and effective ways.

Targeted depletion of TRBV9⁺ T cells induces remission in a single patient with ankylosing spondylitis, with significant improvements in functional and mobility metrics.

In a large multi-cancer cohort, a single liquid biopsy assay enables the detection of four epigenomic modifications, allowing the monitoring of expression of potential drug targets and resistance genes.

Comparison of representation of blind and deaf participants in the All of Us Research Program (AoURP) with CDC national estimates demonstrates that these populations are underrepresented in the AoURP cohort, raising concerns about the generalizability of findings generated using this dataset.

Pre-exposure prophylaxis (PrEP) with daily antiretrovirals to prevent human immunodeficiency virus type 1 acquisition has not been shown to be consistently effective in cisgender women. Modeling adherence to daily PrEP clarifies how robust protection can be achieved.

Modeling shows that antiretroviral treatment as pre-exposure prophylaxis (PrEP) can be highly effective in cisgender women at preventing HIV-1 acquisition, but underscores the need to understand the barriers that limit PrEP adherence in women.

Human immunodeficiency virus type 1 (HIV-1)-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may be able to elicit a durable antibody response.

A model investigating 26 possible malaria treatment policy intervention scenarios showed that introducing multiple first-line antimalarial therapies is the most effective single policy change in slowing the spread of artemisinin-resistant pfkelch R561H mutations in Rwanda over 5 years.

A new framework for linking metagenomic data on the gut microbiome to human traits uncovers bacterial SNPs that associate with BMI in geographically independent cohorts.

Distinct signatures of the airway microbiota associate with acute respiratory distress syndrome, hospital-acquired pneumonia and prolonged mechanical ventilation, and may help to inform clinical outcomes in critically ill patients.

In a pilot feasibility study involving recipients of allogeneic hematopoietic stem cell transplants, adherence to a dietary intervention and its effects on the gut microbiota were assessed in the run-in to a study testing the effects of modulation of the microbiome on transplant outcomes.

The bispecific molecule tebotelimab, which blocks both PD-1 and LAG-3, is well tolerated as a monotherapy and in combination with the anti-HER-2 antibody margetuximab and elicits encouraging clinical activity in solid tumors with high LAG-3 levels and/or expression of IFN-γ-regulated genes.

In a phase 2 trial, the combination of gemcitabine, cisplatin and anti-PD-1 led to a clinical complete response in 43% of patients with muscle-invasive bladder cancer, which facilitated bladder sparing and was associated with long-term bladder-intact metastasis-free survival.

In this pre-specified interim analysis, patients with resected stage IIB/C melanoma who received adjuvant nivolumab had significantly prolonged recurrence-free survival compared to placebo-treated patients, providing another treatment option for this population.

In the ongoing phase 1/2 BNT211-01 trial, CLDN6-specific chimeric antigen receptor (CAR)-T cells given with or without CARVac, a CAR-T cell-amplifying RNA vaccine, were well-tolerated and exhibited encouraging clinical activity in patients with relapsed or refractory CLDN6-positive solid tumors, with the highest response rate in patients with germ cell tumors.

A spinal cord neuroprosthesis targeting leg motor neurons in real time improves walking and reduces freezing of gait in non-human primate models and in one individual with advanced Parkinson’s disease.

Microglia mediate the early and selective degeneration of corticostriatal synapses and the development of cognitive deficits in presymptomatic Huntington’s disease via the complement cascade.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Results from the DiViD Intervention, a phase 2 randomized, placebo-controlled trial, showed that antiviral treatment with pleconaril and ribavirin for 6 months resulted in higher endogenous insulin production in children and adolescents with new-onset type 1 diabetes.

In the SURMOUNT-3 trial, once-weekly treatment with tirzepatide was demonstrated to result in clinically meaningful additional weight loss in adults with overweight or obesity following initial successful weight loss of at least 5% body weight with intensive lifestyle intervention.

In the phase 3 MAESTRO-NAFLD-1 trial, the liver-targeted thyroid hormone receptor-β selective agonist resmetirom was well tolerated and improved liver biomarkers in adults with nonalcoholic fatty liver disease.

A systematic review, combined with a stakeholder survey, presents an overview of current practices and recommendations for dataset curation in health, with specific focuses on data diversity and artificial intelligence-based applications.

SteatoSITE is an open resource that integrates histopathologic assessments, transcriptomic data and longitudinal electronic health records for a cohort of 940 patients with metabolic dysfunction-associated steatotic liver disease.