Volume 28 Issue 10, October 2022

Nature Medicine explores the latest translational and clinical research news

Dogs develop diseases similar to those of humans, and their inbred genetics makes them a useful model for disease biology, allowing the development of new therapies for veterinary and human use.

Hematopoietic stem-cell gene therapy has proven to be an effective treatment for several primary immunodeficiencies, and yet companies in this space are withdrawing from the EU market. Technological and regulatory innovations and a change to cost–benefit models are needed so that rare disease patients can receive these life-saving medicines.

Paying individual people for their health data will widen inequalities and reduce altruism, luring people to sell their privacy. Health data should instead be treated as collective property, and commercial profits should be shared with the public.

Wastewater monitoring has been used to identify SARS-CoV-2 outbreaks and track new variants. This sentinel system should be expanded to monitor other pathogens and boost public health preparedness.

Machine learning algorithms are a powerful tool in healthcare, but sometimes perform no better than traditional statistical techniques. Steps should be taken to ensure that algorithms are not overused or misused, in order to provide genuine benefit for patients.

The Global Burden of Disease provides essential data for evidence-based healthcare, but could be improved by investment in health data systems in low- and middle-income countries

Although questions remain about several diet and disease associations, current evidence supports dietary guidelines to limit red meat and increase vegetable intake.

New analyses are prompting a shift in how we think about systolic blood pressure, with substantial benefits to be gained from population-wide interventions alongside targeting high-risk groups.

Challenges that characterize weight-loss drug trials necessitate good trial design — as highlighted by the STEP 5 trial of semaglutide.

A phase 2 study fails to meet its primary endpoint, but the treatment — a glucagon receptor antagonist — shows clinically relevant improvements in glycemic control, warranting further investigation as a potential adjunct to insulin.

Following a single infusion of CD19-targeting CAR T cells, five patients with SLE showed reduction in disease activity and disease markers; long-term follow-up of these patients and larger trials are now key priorities.

Serial heart MRI scans conducted in previously well people with mild initial COVID-19 illness suggest that lingering cardiac symptoms may be explained, at least in part, by ongoing mild cardiac inflammation.

CAR-mediated trogocytosis contributes to dysfunction of natural killer (NK) cells by promoting fratricide and is an important mechanism of relapse after CAR-NK cell therapy. This problem can be overcome using a dual-CAR strategy that incorporates a dominant-negative signal to prevent NK cell fratricide and exhaustion, while sparing the CAR-activating signal against tumor targets.

Colorectal cancers expressing the mutant BRAF^V600E comprise 10% of all metastatic colorectal cancers, present with a poor prognosis, and are refractory to common therapies. We discovered that a subgroup of these tumors that carries loss-of-function RNF43 mutations is associated with significantly improved response to the current standard-of-care anti-BRAF–anti-EGFR combination therapy.

The identification of KRAS^G12C inhibitors has reignited interest in targeting RAS proteins. This work describes the discovery of the KRAS^G12D-specific inhibitor MRTX1133 and demonstrates the feasibility of potently and selectively targeting this oncogenic variant. MRTX1133 treatment markedly inhibited KRAS-dependent signaling and induced tumor regression in xenograft models harboring the KRAS^G12D mutation.

This Perspective reflects on the past, present and future of the dynamic, expanding public health endeavor that is the Global Burden of Disease Study.

This Review discusses the impact of COVID-19 on mental health, from pandemic-related societal effects to direct infection-related neuropsychiatric sequelae, highlighting the lessons learned and outstanding knowledge gaps.

A new Burden of Proof meta-analytic method that accounts for between-study heterogeneity and corrects for bias between different study designs is used to interpret the strength of evidence between different pairs of risk factors and health outcomes.

A meta-analysis using the Burden of proof method reported consistent evidence supporting harmful associations between smoking and 28 different health outcomes.

A systematic review using the burden of proof meta-analytic method found a significant harmful effect between high systolic blood pressure and ischemic heart disease.

A meta-analysis using the Burden of Proof function identified modest evidence supporting a protective role of vegetable consumption against ischemic heart disease, stroke and esophageal cancer but not type 2 diabetes.

Using the burden of proof analytical tool, a meta-analysis found weak or no evidence of associations between unprocessed red meat consumption and increased risk of six cardiometabolic disease and cancer outcomes.

Results from the STEP 5 trial, testing semaglutide as an adjunct to behavioral interventions in adults with overweight or obesity, demonstrate sustained weight loss over a period of 104 weeks.

A phase 2 study testing glucagon receptor antagonist volagidemab as an adjunct to insulin therapy in patients was found to be safe and tolerable. Although the primary endpoint of reduction in daily insulin usage was not met, volagidemab therapy was associated with improved glycaemic control compared to placebo.

A new study examines microbiome-generated ethanol in individuals with and without nonalcoholic fatty liver disease (NAFLD), concluding that microbial ethanol might contribute to pathogenesis in some patients with NAFLD.

A machine learning algorithm can predict the future risk of idiopathic pulmonary fibrosis, a disease that is difficult to diagnose at its early stages, based on comorbidity signatures in electronic health records.

In individuals with long-term cardiac symptoms after an initially mild course of COVID-19 illness, magnetic resonance imaging and measurement of cardiac injury biomarkers commonly detected ongoing cardiac inflammation but not structural heart disease.

Results from a study of five patients with refractory systemic lupus erythematosus, who were treated with anti-CD19 CAR T cell therapy under a compassionate-use program, demonstrate remission of SLE disease with follow-up of up to 17 months.

A new dual-chimeric antigen receptor (CAR) system enhances the antitumor activity of CAR natural killer cells and makes them less susceptible to therapeutic resistance in preclinical models.

Analysis of outcomes of over 800 patients with relapsed/refractory diffuse large B cell lymphoma, treated with commercially available CAR T cell therapy, supports higher efficacy and also a higher toxicity of axicabtagene ciloleucel compared to tisagenlecleucel as the third or more treatment line for this type of tumor.

In a single-arm, non-randomized trial, neoadjuvant atezolizumab therapy in a large cohort of patients with resectable non-small cell lung cancer was safe and the study met its primary end point of major pathological response ≥15%.

The presence of inactivating mutations in RNF43, a negative regulator of WNT, in tumor cells predicts improved response rates and survival outcomes in patients with metastatic BRAF^V600E colorectal cancer treated with anti-BRAF/EGFR therapy.

A potent and selective inhibitor of KRAS^G12D, the most common mutant form of the KRAS oncoprotein, has anti-tumor efficacy in multiple pre-clinical cancer models, opening the possibility to therapeutically target this highly prevalent oncogenic driver.

The SIGNAL Phase 2 study of pepinemab immunotherapy in early Huntington’s disease (HD) did not meet its coprimary clinical efficacy endpoints, but had a favorable safety profile and showed a significant treatment-related reduction in caudate brain atrophy and reversal of the characteristic decline in brain metabolic activity that is typical of HD progression.

Empirically based models of disease progression in familial frontotemporal dementia reveal the relative ordering of clinical, neuroimaging, and fluid biomarker changes and facilitate novel clinical trial designs

Using a neural network-based model, Parkinson’s disease can be diagnosed and its severity monitored based on breathing patterns while someone is asleep, with the potential for at-home touchless monitoring.