Volume 30 Issue 3, March 2024

Growing evidence shows that lower doses or shorter treatments of precision cancer therapies could reduce toxicity and save money — but more clinical trials are needed.

Health impacts from climate change have been apparent for at least 20 years, but the climate crisis is still not treated like other global public health emergencies.

Drawing from real-life scenarios and insights shared at the RAISE (Responsible AI for Social and Ethical Healthcare) conference, we highlight the critical need for AI in health care (AIH) to primarily benefit patients and address current shortcomings in health care systems such as medical errors and access disparities.

Digital health technologies can be used to reduce disparities in cardiovascular care, but improved digital access and literacy are needed.

Electronic health information, including from electronic health records, is needed to develop AI tools for health, but the seamless flow of data will require standards and interoperability.

The US Supreme Court decision on affirmative action will disrupt efforts to diversify the physician–scientist workforce and requires immediate action.

A new study shows the benefits of treating anxiety to prevent postnatal depression — and highlights the need for more pragmatic research to simplify treatment packages, address other comorbid symptoms, and deliver effective perinatal mental health care at scale.

A flurry of emerging treatment options is transforming the therapeutic landscape of hepatocellular carcinoma; two new studies highlight the complexities and gaps in knowledge, but also hint at a greater understanding of how to apply immunotherapy in early and advanced disease.

After many lean years, important progress has been made in updating the anti-tuberculosis drug armamentarium; a new drug that targets bacterial protein synthesis is one of several that could help transform the treatment of this neglected and deadly disease.

Longitudinal analysis of stool samples reveals new insights into how the gut microbiome changes during immunotherapy. These findings could inform the application of microbiome-targeted interventions to maximize the outcomes of immune checkpoint blockade.

Acute kidney injury affects one in five hospitalized patients and can lead to lasting kidney damage or death. We show that clonal hematopoiesis of indeterminate potential — a common age-related condition caused by blood cell mutations — increases the risk of acute kidney injury in multiple cohorts of human patients and in mouse models.

Primary fetal organoids are currently derived from tissue samples obtained at termination of pregnancy. We developed an approach that enables prenatal derivation of epithelial organoids from fetal fluids. Single-cell mapping of the human amniotic fluid content unveiled the presence of viable fetal epithelial progenitors of multiple tissues that can form fetal lung, kidney and intestinal organoids.

Patient-reported outcomes are invaluable tools, but may impose a burden on patients; this consensus statement provides a set of 19 recommendations to reduce respondent burden.

Self-care interventions have the potential to improve health coverage for women while offering greater agency and autonomy, but only if certain barriers—such as stigma and cost—can be overcome.

In an analysis of severe dengue cases in a cohort of children in India, more than half could be attributed to primary rather than secondary infection, suggesting that primary dengue infections might also contribute substantially to severe disease burden.

In a phase 3 trial, an anxiety-focused cognitive behavioral therapy intervention delivered during pregnancy by non-specialist providers in Pakistan reduced the incidence of postnatal depression and anxiety compared to enhanced care.

An interrupted time series analysis found that the World Health Organization Framework Convention for Tobacco Control reduced smoking prevalence across 170 countries (excluding China) since the country-specific year of ratification.

An observational study reports the joint effects of polygenic risk scores and radiation treatment exposure with a subsequent increased risk of multiple solid cancers in two large cohorts of survivors of childhood cancer.

In the phase 2 RENOBATE trial, the combination of regorafenib and nivolumab as first-line treatment for unresectable hepatocellular carcinoma exhibited a safe profile and met the primary endpoint with a 31% overall response rate.

Results from a multicenter, randomized phase 2 trial in China show that adjuvant anti-PD-1 therapy in patients with resected hepatocellular carcinoma with microvascular invasion leads to prolonged recurrence-free survival compared to active surveillance.

In the phase 2 HUDSON study, patients with advanced non-small-cell lung cancer received anti-PD-L1 combined with biomarker-guided therapy targeting ATR kinase, PARP, STAT3 or CD73, leading to encouraging clinical benefit in response to combination of the ATR kinase inhibitor ceralasertib with durvalumab.

In an exploratory preplanned biomarker analysis of the phase 3 PARADIGM trial, a lack of resistance gene alterations in baseline circulating tumor DNA (negative hyperselection) was associated with prolonged overall survival after first-line panitumumab with chemotherapy in patients with RAS wild-type metastatic colorectal cancer.

In a prespecified interim analysis of the phase 3 trial GEMSTONE-304, anti-PD-L1 with chemotherapy versus chemotherapy alone led to significantly prolonged progression-free survival and overall survival of patients with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma.

Cohort-scale integration of clinical and proteomic data from tumor tissues in patients with pancreatic ductal adenocarcinoma led to the identification of a prognostic risk model for patient stratification as well as biomarkers of response to adjuvant chemotherapy, validated in independent external cohorts.

In this first-in-human phase 1 dose-escalation trial of OMO-103, a MYC inhibitor, in patients with solid tumors, treatment was safe and showed preliminary clinical activity along with demonstrated target engagement and identification of potential pharmacodynamic markers.

In the final report of a phase 1/2 trial evaluating allogeneic CD19-specific CAR-NK cells armored with IL-15 in patients with CD19⁺ hematologic malignancies, the therapy was shown to be safe and efficacious with distinct cord blood features associated with response.

Understanding the dynamics of the gut microbiota over the course of cancer treatment regimens and their associated adverse events can help identify microbial features that associate with response to immune checkpoint blockade.

Efforts to identify microbial signatures of response to immune checkpoint blockade suggest that strain-level associations may be cancer type agnostic but cancer therapy specific.

Clonal hematopoiesis, which increases with age and is implicated in a variety of age-related diseases, is shown here to be associated with a greater risk of acute kidney injury and worse outcome following injury, as demonstrated using multiple patient cohorts, Mendelian randomization analysis and mechanistic studies in mouse disease models.

Sex-stratified genome-wide association studies identify loci showing sex-specific effects on blood pressure, allowing for the development of sex-specific polygenic risk scores for blood pressure traits.

Denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, previously developed for osteoporosis, was shown to be effective at inducing structural modification in patients with erosive hand osteoarthritis after 24 weeks.

A large-scale study examined the heterogeneous effects of artificial intelligence (AI) assistance on 140 radiologists across 15 chest X-ray diagnostic tasks and found that conventional experience-based factors, such as years of experience, subspecialty and familiarity with AI tools, fail to reliably predict the impact of AI assistance.

Pretrained using over 100,000 diagnostic histopathological slides across 20 major tissue types, a self-supervised model is shown to outperform existing baselines across various clinically relevant computational pathology tasks.

Developed using diverse sources of histopathology images, biomedical text and over 1.17 million image–caption pairs, evaluated on a suite of 14 diverse benchmarks, a visual-language foundation model achieves state-of-the-art performance on a wide array of clinically relevant pathology tasks.

The generation of primary organoids, from fetal fluid-derived epithelial stem or progenitor cells, offers the possibility of modeling different developing tissues during gestation, even beyond the limits of pregnancy termination.

Integrated analysis of clinical, serological and behavioral data estimates that current clinical surveillance systems detect only 1 of 3,280 true community infections in a cholera-endemic region of Bangladesh.

A new inhibitor of Mycobacterium tuberculosis leucyl-tRNA synthetase is associated with bactericidal activity in humans and may be a candidate for combination therapy of tuberculosis.