Two early-phase clinical trials show impressive response rates and symptom improvement with the selective KIT inhibitor avapritinib, which will provide a much-needed new treatment option for patients.

Advanced systemic mastocytosis (AdvSM) is a rare hematologic neoplasm driven by the KIT D816V mutation and associated with poor survival. This phase 1 study (NCT02561988) evaluated avapritinib (BLU-285), a selective KIT D816V inhibitor, in patients with AdvSM. The primary endpoints were the maximum tolerated dose, recommended phase 2 dose and safety of avapritinib. Secondary endpoints included overall

Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase 2 trial (no. NCT03580655) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200 mg in patients

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) injected periodically have been shown to not increase and, for some members of this class, decrease the risk of cardiovascular events. The cardiovascular safety of delivering a continuous subcutaneous infusion of the GLP-1RA exenatide (ITCA 650) is unknown. Here, we randomly assigned patients with type 2 diabetes with, or at risk for, atherosclerotic

Lessons from the rapid development, manufacture and distribution of vaccines against COVID-19 must be broadly applied to expedite vaccine development for other infectious diseases.

Despite the success of antiretroviral therapy (ART) for people living with HIV, lifelong treatment is required and there is no cure. HIV can integrate in the host genome and persist for the life span of the infected cell. These latently infected cells are not recognized as foreign because they are largely transcriptionally silent, but contain replication-competent virus that drives resurgence of the

In a phase 1/2 trial, an investigational gene therapy brought about sustained expression of clotting factor VII and a dramatic reduction in the bleeding rate.

Early detection of infectious diseases is crucial for reducing transmission and facilitating early intervention. In this study, we built a real-time smartwatch-based alerting system that detects aberrant physiological and activity signals (heart rates and steps) associated with the onset of early infection and implemented this system in a prospective study. In a cohort of 3,318 participants, of whom

Being transgender can inspire these researchers and improve their work, but sometimes their research has nothing to do with their identity.

New research can help policymakers make evidence-based decisions about the risks and benefits of in-person schooling; strategic use of the available data will be key to getting this right.

New equations to estimate kidney function enable accurate clinical assessment without the use of race as a modifier.

An anti-tick mRNA vaccine shows promise in guinea pigs, causing early detachment and reduced transmission of Lyme disease–causing pathogens.

Collection of data on sexual orientation, gender identity and intersex status will help to reduce health disparities that affect people from sexual and gender minority communities.

The particularly interdisciplinary nature of human microbiome research makes the organization and reporting of results spanning epidemiology, biology, bioinformatics, translational medicine and statistics a challenge. Commonly used reporting guidelines for observational or genetic epidemiology studies lack key features specific to microbiome studies. Therefore, a multidisciplinary group of microbiome

Polygenic risk scores (PRSs) aggregate the many small effects of alleles across the human genome to estimate the risk of a disease or disease-related trait for an individual. The potential benefits of PRSs include cost-effective enhancement of primary disease prevention, more refined diagnoses and improved precision when prescribing medicines. However, these must be weighed against the potential risks

Bifidobacterium species enriched in breastfed infants produce metabolites that strengthen infants’ gut barrier and immune systems.

Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing

STEMM organizations must be proactive in advancing diversity, equity and inclusion.

Racial equity and global inclusion are essential if biomedical science is to fulfil its mission to improve human health.

Funders’ goals for diversity, equity and inclusion are laudable, but they will only be successful if the funders prioritize health disparities research and address biases in the funding application process.

The National Institutes of Health (NIH) is committed to increasing the participation of underrepresented groups in science and medicine, through changes in our funding and recruitment processes. These actions provide a blueprint for the global research community.

New studies highlight the immunological benefits of COVID-19 vaccine boosters, but questions remain over how to best make use of a limited global supply.

SGLT-2 inhibitors show promise for treatment of heart failure with preserved ejection fraction, but clinical data are nuanced. Appropriate endpoint selection will be key to deciphering their benefits.

We are launching a series on Diversity, Equity and Inclusion in medical research and are redoubling our commitment to representation in our pages.

The applicability of circulating tumor DNA (ctDNA) genotyping to inform enrollment of patients with cancer in clinical trials has not been established. We conducted a phase 2 trial to evaluate the efficacy of pertuzumab plus trastuzumab for metastatic colorectal cancer (mCRC), with human epidermal growth factor receptor 2 (HER2) amplification prospectively confirmed by tumor tissue or ctDNA analysis

A HPV vaccination program in England has almost completely eliminated cervical cancer in women who were vaccinated at the age of 12–13 years.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is rarely fatal in children and young people (CYP, <18 years old), but quantifying the risk of death is challenging because CYP are often infected with SARS-CoV-2 exhibiting no or minimal symptoms. To distinguish between CYP who died as a result of SARS-CoV-2 infection and those who died of another cause but were coincidentally

A translational study reveals a role for interleukin-1–fibroblast–neutrophil signaling in drug-resistant inflammatory bowel disease, opening a potential path to targeted treatment.

A phase 3 study with dalpiciclib reinforces the efficacy of CDK4/6 inhibitors in select patients with metastatic breast cancer; with several such inhibitors available, more evidence is needed to help guide treatment decisions.

Mesothelioma is a rare and fatal cancer with limited therapeutic options until the recent approval of combination immune checkpoint blockade. Here we report the results of the phase 2 PrE0505 trial (NCT02899195) of the anti-PD-L1 antibody durvalumab plus platinum-pemetrexed chemotherapy for 55 patients with previously untreated, unresectable pleural mesothelioma. The primary endpoint was overall survival

Bruton’s tyrosine kinase (BTK) is crucial for FcεRI-mediated mast cell activation and essential for autoantibody production by B cells in chronic spontaneous urticaria (CSU). Fenebrutinib, an orally administered, potent, highly selective, reversible BTK inhibitor, may be effective in CSU. This double-blind, placebo-controlled, phase 2 trial (EudraCT ID 2016-004624-35) randomized 93 adults with ant

Blockade of the cyclin-dependent kinase 4 and 6 pathway has been shown to be effective in the treatment of hormone receptor-positive advanced breast cancer (ABC). We report the interim results of DAWNA-1 (NCT03927456), a double-blind, randomized, phase 3 trial of dalpiciclib (a new cyclin-dependent kinase 4 and 6 inhibitor) plus fulvestrant in hormone receptor-positive, HER2-negative ABC with disease

AI-based analysis reveals clusters of patients with distinct responses to β-blockers, which could help to personalize treatment and improve survival.

The effectiveness of the coronavirus disease 2019 (COVID-19) BNT162b2 vaccine in preventing disease and reducing viral loads of breakthrough infections (BTIs) has been decreasing, concomitantly with the rise of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear whether the observed decreased effectiveness of the vaccine in reducing viral loads

With the global expansion of the highly transmissible SARS-CoV-2 Delta (B.1.617.2) variant, we conducted a matched test-negative case–control study to assess the real-world effectiveness of COVID-19 messenger RNA vaccines against infection with Delta in Qatar’s population. BNT162b2 effectiveness against any, symptomatic or asymptomatic, Delta infection was 45.3% (95% CI, 22.0–61.6%) ≥14 d after the

Greater convergence between national regulators will help prepare for the next pandemic

In normal epithelium, mutant clones compete with emerging tumors for space and survival, helping to curb early cancer development.

Patients with heart failure and preserved ejection fraction (HFpEF) have a high burden of symptoms and functional limitations, and have a poor quality of life. By targeting cardiometabolic abmormalities, sodium glucose cotransporter 2 (SGLT2) inhibitors may improve these impairments. In this multicenter, randomized trial of patients with HFpEF (NCT03030235), we evaluated whether the SGLT2 inhibitor

Certain infected individuals suppress human immunodeficiency virus (HIV) in the absence of anti-retroviral therapy (ART). Elucidating the underlying mechanism(s) is of high interest. Here we present two contrasting case reports of HIV-infected individuals who controlled plasma viremia for extended periods after undergoing analytical treatment interruption (ATI). In Participant 04, who experienced viral

Among tool kits to combat the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, school closures are one of the most frequent non-pharmaceutical interventions. However, school closures bring about substantial costs, such as learning loss. To date, studies have not reached a consensus about the effectiveness of these policies at mitigating community transmission

The role that traditional and hybrid in-person schooling modes contribute to the community incidence of SARS-CoV-2 infections relative to fully remote schooling is unknown. We conducted an event study using a retrospective nationwide cohort evaluating the effect of school mode on SARS-CoV-2 cases during the 12 weeks after school opening (July–September 2020, before the Delta variant was predominant)

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive

During androgen-deprivation therapy, certain bacteria in the gut can synthesize androgens, thereby promoting tumor progression and therapy resistance.

Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology and in situ localization across three cohorts of patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular inflammatory response in IBD that map to distinct histopathological and

The COVID-19 pandemic has exacerbated the already substantial burden of depression and anxiety, with tens of millions of additional cases reported globally in 2020.

RNA interference (RNAi) for spinocerebellar ataxia type 1 can prevent and reverse behavioral deficits and neuropathological readouts in mouse models, with safety and benefit lasting over many months. The RNAi trigger, expressed from adeno-associated virus vectors (AAV.miS1), also corrected misregulated microRNAs (miRNA) such as miR150. Subsequently, we showed that the delivery method was scalable,

Genes involved in distinct diabetes types suggest shared disease mechanisms. Here we show that One Cut Homeobox 1 (ONECUT1) mutations cause monogenic recessive syndromic diabetes in two unrelated patients, characterized by intrauterine growth retardation, pancreas hypoplasia and gallbladder agenesis/hypoplasia, and early-onset diabetes in heterozygous relatives. Heterozygous carriers of rare coding

Clonal hematopoiesis (CH) results from somatic genomic alterations that drive clonal expansion of blood cells. Somatic gene mutations associated with hematologic malignancies detected in hematopoietic cells of healthy individuals, referred to as CH of indeterminate potential (CHIP), have been associated with myeloid malignancies, while mosaic chromosomal alterations (mCAs) have been associated with

Under-reporting of fatal police violence is rife within the US government–run database — intervention strategies are urgently needed to quantify and address this public-health issue

A study shows that monozygotic (‘identical’) twins can be identified by a distinct epigenetic signature, shedding light on a process that has been shrouded in mystery.

The effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found

New strategies based on nucleic acid technologies are being exploited to treat chronic hepatitis B—a pilot clinical study of antisense oligonucleotide treatment shows the potential promise of this approach.

During the COVID-19 pandemic, the public have turned to scientists and doctors for vital information. But science communication is a skill in itself, so we asked the experts to share their tips.

A new spatial analysis calls for a tiered and geographically targeted approach to tackling the vast, ongoing burden of anemia in women within low- and middle-income countries.