Volume 28 Issue 6, June 2022

Designing a new drug is not enough; it has to be delivered to its target, which can be achieved via a cornucopia of vehicles, from nanoparticles and microneedles to red blood cells and microalgae.

Rapid communication of clinical trial results has likely saved lives during the COVID-19 pandemic and should become the new norm.

Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.

Forcibly displaced persons, such as refugees, are at an increased risk of physical and mental health conditions and would therefore benefit from novel healthcare technologies, research on which can be conducted under an ethical framework.

Patient-reported outcomes are increasingly collected in clinical trials and in routine clinical practice, but strategies must be taken to include underserved groups to avoid increasing health disparities.

Mental health services often seek to increase supply, without considering demand, which can be addressed by matching care to the needs and preferences of users.

A phase 3 trial highlights the importance of problem-led design, multidisciplinary commitment and patient-reported outcomes — with skilled oncology nurses having a crucial role.

Biopsies from synovial joints — and the abundance of B cells and macrophages therein — may instruct more effective treatment decisions for individuals with rheumatoid arthritis.

New technologies allow the noninvasive detection and staging of asymptomatic alcohol-associated liver disease; further refinement of this approach could transform clinical management and improve patient outcomes.

Preventing atherosclerotic cardiovascular disease in adults will require innovative public health approaches focused on children and families, to improve risk factor trajectories across the lifespan and prioritize children at highest risk of future disease.

Experiencing a mental health crisis has a detrimental impact on a patient’s life. A machine learning algorithm trained retrospectively with electronic health records can predict almost 60% of mental health crises 4 weeks in advance. Prospective evaluation of the algorithm in clinical practice reveals its potential to enable preemptive interventions.

Substance addiction is a major public health crisis. Neuromodulation treatments show promise, but the therapeutic targets remain unclear. Studying human brain lesions that led to addiction remission with the lesion-network-mapping approach resulted in the identification of a brain circuit shared across addiction disorders that may have therapeutic potential.

A prospective clinical study evaluating patients 28–60 days after hospitalization for COVID-19 reveals increased cardio-renal inflammation, reduced lung function and poorer self-reported clinical outcomes in patients relative to that in control participants.

The authors propose a new conceptual model of critical illness that moves away from the current syndrome-based framework in favor of more precise biological descriptors—spurred by mounting translational evidence and insights from Coronavirus Disease 2019 (COVID-19) research.

Restoration of visual function in degenerative retinal disease may be an attainable goal, thanks to advances in cell-based therapy, gene therapy, and prosthetics. This Review discusses the most promising strategies that will probably reach clinical use in the next decade.

A new study reveals that polygenic scores for lipid traits derived from data of African American individuals have high predictive value in a South African Zulu cohort but are poor predictors in a cohort from Uganda, further highlighting the need to improve polygenic predictions in populations of African ancestries.

In a randomized phase 2 trial, sotigalimab, a CD40 agonist, did not significantly improve overall survival in patients with previously untreated metastatic pancreatic cancer when combined with chemotherapy or with nivolumab and chemotherapy. Multi-omic exploratory analyses provide insights into immunologic features associated with clinical benefit.

Results from the PRADO extension cohort of the OpACIN-neo trial show that pathologic response rate to neoadjuvant ipilimumab and nivolumab can be used as a criterion for personalization of further treatment in stage III nodal melanoma, with the potential to reduce treatment morbidity and increase patient quality of life.

In an interim analysis of a phase 1 trial, CAR T cells specific for Claudin18.2, a tight junction protein isoform highly expressed on gastrointestinal tract tumors, were well-tolerated and exhibited promising clinical activity in patients with gastrointestinal cancers.

In a trial of patients with soft-tissue sarcomas, clinical outcome measures following anti-PD-1 treatment were better in a cohort prospectively selected for the presence of intratumoral tertiary lymphoid structures than in other cohorts where most patients lacked these structures.

Lineage tracing analyses of cells from two monozygotic twins presenting with myelofibrosis in adulthood provide evidence of in utero transplacental transmission of the tumorigenic clone.

A novel gene expression classifier of AML heterogeneity captures patient-specific variation in leukemia cell composition and predicts clinical responses to treatment.

The phase 3 CAPRI clinical trial evaluating the impact of a digital nurse navigator-led system in patients receiving oral anticancer treatment shows that remote monitoring using a smartphone app results in an improved patient care experience and optimizes healthcare resources.

A decentralized, privacy-preserving machine learning framework used to train a clinically relevant AI system identifies actionable molecular alterations in patients with colorectal cancer by use of routine histopathology slides collected in real-world settings.

Machine learning applied on electronic health records can predict mental health crises 28 days in advance and become a clinically valuable tool for managing caseloads and mitigating the risk of crisis.

Lesions resulting in addiction remission occur in multiple different brain locations but map to a specific brain circuit.

Biomarker analysis of the phase 4 R4RA trial identifies pretreatment synovial biopsy features selectively associated with response to rituximab or tocilizumab, and leads to the development of models that might predict treatment benefit in patients with rheumatoid arthritis

New data from a 2 × 2 factorial randomized, controlled trial shows that empagliflozin improves time in range in patients with type 1 diabetes using a closed-loop automated insulin delivery system.

Interogation of mass-spectrometry-based proteomics of liver and plasma from a cohort of patients with alcohol-related liver disease identifies noninvasive biomarkers associated with early stages of disease progression, including significant fibrosis, inflammation and steatosis.

A combination of three monoclonal antibodies transiently reduced viremia in people living with HIV-1 and not on antiretroviral therapy, but it did not prevent viral rebound. Further studies are needed to determine if this approach can be optimized.

Therapeutic antibodies, and sera from immunocompromised individuals prophylactically treated with therapeutic antibodies, differ in neutralizing activity against the SARS-CoV-2 Omicron BA.1 and BA.2 sublineages, which could have implications for pre-exposure and post-exposure treatment.

Deep clinical phenotyping at 28–60 days post-discharge of patients who had been hospitalized with COVID-19 and subsequent long-term follow-up with electronic health records reveal evidence of persistent cardio-renal involvement.

An interrupted time series analysis of 31 healthcare services in ten low-income, middle-income and high-income countries demonstrates that the COVID-19 pandemic caused immediate, heterogeneous and prolonged disruptions in service delivery, highlighting the need for health system resilience in pandemic preparedness.