Volume 29 Issue 2, February 2023

Nature Medicine explores the latest translational and clinical research news, with an immunotherapy that delays the onset of type 1 diabetes in high-risk children and adults.

Telehealth is poised to grow into big business in Africa, with home-grown and imported start-ups offering child and maternal health education, remote diagnosis, prescription services and more.

The drug-scheduling system, particularly the approach to rescheduling, should be reformed to ensure all beneficial medicines, including marijuana and psilocybin, are available to scientists and patients.

Data sharing enhances the value of medical research and builds trust in clinical trials, but more biomedical researchers need to be trained in these approaches, which include meta-research, data science and ethical, legal and social issues.

As China amends its ‘zero COVID’ strategy, mitigation measures are needed to reduce transmission.

A study showing feasibility and preliminary efficacy of off-the-shelf CAR T cells represents steady progress on the long road to clinical use.

Pre-symptomatic gene editing in preclinical models of hypertrophic cardiomyopathy shows therapeutic promise; clinical studies are now needed to assess safety and efficacy in humans.

In a phase I trial, the combination of dabrafenib, trametinib and spartalizumab uncovers the crosstalk between the MAPK pathway and the immune system, which offers a promising new strategy to improve clinical outcomes.

A study prospectively evaluating a stratified approach to selecting treatment heralds a new era of precision medicine for type 2 diabetes, which should incorporate ongoing discovery, social determinants of health and healthcare transformation.

Tumor mutation burden is an imperfect predictor of response to immunotherapies. Mutations in regions of the genome unlikely to undergo loss during tumor evolution constitute a persistent tumor mutation burden that may drive sustained immunological tumor control in the context of cancer immunotherapy.

Smoldering multiple myeloma is an asymptomatic precursor condition to multiple myeloma, a cancer in the bone marrow. We conducted a population-based screening study — in which 51% of the population over 40 years of age in Iceland participated — and found that the prevalence of smoldering multiple myeloma was 0.5% in the study population.

The largest whole-exome sequencing study of individuals with premature ovarian insufficiency (POI) so far identifies 20 new disease-associated genes, yields an overall genetic contribution to POI of 23.5%, and provides detailed characterization of the genetic landscape of this disorder.

This Review provides a timely overview of new technological advances and treatment approaches, with a particular emphasis on brain-circuit-based interventions for precision psychiatry.

This Review discusses the effect of comorbidities and multimorbidity on the three mechanistically distinct phases of COVID-19, evaluating the evidence in the context of confounding factors and our evolving understanding of the disease.

Circulating variants of SARS-CoV-2 continue to evade neutralization by COVID-19 vaccines, including bivalent boosters that target the BA.4/BA.5 variants of concern, suggesting that strategies to get ahead of the virus’ evolution might be warranted.

An analysis of sera samples collected between January and July of 2022 in Hong Kong shows that the effectiveness of both the BNT162b2 and CoronaVac COVID-19 vaccines against SARS-CoV-2 Omicron BA.2 variant infection waned rapidly after the third and fourth doses.

Analysis of data from California prisons shows that both COVID-19 vaccination and prior SARS-CoV-2 infection reduces the risk of virus transmission to close contacts.

In the third annual iteration of a survey assessing vaccine confidence in 23 high-income, middle-income and low-income countries, although results were heteregeous across countries, overall willingness to accept a COVID-19 vaccine was found to have increased.

Using a randomized three-way crossover design and stratification approaches based on obesity and renal function in people with type 2 diabetes, the TriMaster study demonstrated that patients with obesity were more likely to have greater glycemic control with pioglitazone (a thiazolidinedione) than with sitagliptin (a DPP4 inhibitor) and that patients with eGFR 60–90 ml/min/1.73 m² were more likely to achieve lower HbA1c levels on sitagliptin than on canagliflozin (an SGLT2 inhibitor).

A prespecified secondary endpoint from the TriMaster study demonstrates that after trying three different classes of diabetes medications most patients preferentially selected the drug that was associated with the best glycemic control on an individual level.

The FLIGHT-FXR trial, testing farnesoid X receptor agonist tropifexor in nonalcoholic steatohepatitis, demonstrated sustained decreases in alanine aminotransferase levels and hepatic fat fraction, but not aspartate aminotransferase, with dose-dependent pruritus being the most common adverse event.

Adenine base editing successfully corrected a MYH7 pathogenic variant that causes hypertrophic cardiomyopathy in human cardiomyocytes and a mouse model of the disease, highlighting the potential of the approach to correct monogenic variants causing cardiac disease.

Two approaches using an adenine base editor and a Cas9 nuclease prevented the development of hypertrophic cardiomyopathy in mice carrying a pathogenic mutation on the Myh6 gene, highlighting the potential of single-dose genetic therapies for the treatment of cardiac disease.

In an interim phase 1 trial analysis, escalating doses of off-the-shelf allogeneic anti-BCMA CAR T cells, in combination with an anti-CD52 antibody-containing lymphodepletion regimen, were feasible to administer and exhibited an encouraging safety profile in patients with relapsed or refractory multiple myeloma

A deep learning model trained on multiple tumor immune cell stainings from patients with colorectal cancer outperforms currently used clinical and single tumor immune cell staining-based parameters in predicting prognosis. The model can also predict the response to neoadjuvant therapy.

Genomic analyses in large cohorts of patients with cancer identify a new measure of tumor mutational burden, based on genomic regions that are unlikely to undergo loss, that is associated with therapeutic response to immunotherapy.

Intratumoral injection of the oncolytic virus talimogene laherparepvec (T-VEC) during weekly paclitaxel before neoadjuvant doxorubicin and cyclophosphamide led to clinical benefit and was well tolerated in patients with stage 2–3 triple-negative breast cancer.

Patients with BRAF^V600E-mutated colorectal cancer have encouraging overall response rates to inhibition of PD-1, BRAF and MEK, with translational analyses suggesting that induction of tumor-intrinsic programs and immune programs contributes to improved outcomes via MAPK inhibition.

A nationwide screening program from the iStopMM study performed in Iceland to detect smoldering multiple myeloma reported a prevalence of 0.5% in individuals over 40 years of age, with increasing risks with age and in males.

The combination of anti-PD-1 treatment with cisplatin and 5-fluorouracil in patients with previously untreated, PD-L1-positive esophageal squamous cell carcinoma improved progression-free survival and overall survival.

Whole-exome sequencing analyses in a cohort of 1,030 patients with premature ovarian insufficiency identify new likely pathogenic variants and reveal distinct genetic architectures between primary and secondary amenorrhea.

A smartphone-based system, designed to induce a steady gaze in children using cartoon-like video stimuli, can identify visually impaired children across a wide range of ophthalmic disorders, based on analysis of gazing behaviors and facial features.