Nature Medicine asks leading researchers to name their top clinical trial for 2024, from base editing and a vaccine against HIV to artificial intelligence tools for lung cancer and patient triage.

To the Editor: Lek et al. (Sept. 28 issue)1 report the unexpected death of a patient with Duchenne’s muscular dystrophy (DMD) after recombinant adeno-associated virus serotype 9 (rAAV9)–delivered CRISPR (clustered regularly interspaced short palindromic repeats)–transactivator therapy in an “N-of-1” study. Despite the rigorous planning and precautionary measures, two aspects of the study necessitate

To the Editor: In the ENLIVEN trial, Loomba and colleagues (Sep. 14 issue)1 provided significant evidence regarding the efficacy of pegozafermin in patients with nonalcoholic steatohepatitis (NASH). Almost two thirds of enrolled patients had concomitant type 2 diabetes mellitus, and most were obese. According to the prespecified eligibility criteria, patients who had received stable antidiabetic treatment

To the Editor: Tight glucose control was not shown to improve outcomes in critically ill patients in the TGC-Fast trial conducted by Gunst et al. (Sep. 28 issue).1 However, assessment of glycemic variability (rather than glycemic control alone) might be useful. Critically ill patients are often exposed to high glycemic variation, regardless of whether initial stress hyperglycemia has been corrected;

A trial of tominersen, designed to slow Huntington’s disease progression by lowering levels of huntingtin protein, was stopped prematurely, and an ad hoc analysis of the results at week 69 was carried out.

It is far easier to confront biases in others than in ourselves. But we recognize that the Journal and other medical institutions have in the past justified and advocated the mistreatment of groups on the basis of their race, ethnicity, religion, sex or gender, and physical or mental conditions. We have therefore commissioned an independent group of historians to produce a series of articles covering

Huge improvements in the treatment of many serious diseases have been made in the past half century, during which I have had the privilege of working first as a pediatric oncologist and later as a diabetologist. In the field of pediatric oncology, scientific progress has dramatically changed the prognosis for many forms of cancer from very high mortality to a cure for most children who are affected

In this issue of the Journal, Fakih et al.1 report the results from CodeBreaK 300, a phase 3 trial of the selective Kirsten rat sarcoma viral oncogene homologue (KRAS) glycine-to-cysteine mutation at codon 12 (KRAS G12C) inhibitor sotorasib in combination with the epidermal growth factor receptor (EGFR) inhibitor panitumumab in patients with metastatic colorectal cancer with KRAS G12C mutation. In

The authors discuss adaptive strategies for reducing the risk of climate-sensitive waterborne diseases, such as climate-proofing water treatment and distribution systems and improving early-warning systems.

Background Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody–drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. Methods Download a PDF of the Research Summary. We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the

Background Janus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves β-cell function in type 1 diabetes is unclear. Methods Download a PDF of the Research Summary. In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes

Slavery and the Journal Founded by men whose families profited from slavery, the Journal provided a prominent forum where physicians perpetuated race hierarchies before and after the Civil War.

Quality of life, NHS culture, and challenges around training opportunities are all key issues affecting doctors’ morale Despite the announcement of new strike dates, the recent offer by the government to NHS consultants and progress in conversations between the Department of Health and junior doctor representatives provide hope for resolution of industrial action. Negotiations, and any subsequent offers

Half of all cases of cervical cancer in the UK are diagnosed in women who aren’t up to date in their screening. But the numbers of those turning up for screening have been falling since 2005, and covid has caused further disruption. The NHS has trialled posting DIY human papillomavirus (HPV) testing kits directly to “non responders,” and the question is whether it would be a good strategy for everyone

Questions remain as to why long covid wasn't a political priority, writes Ondine Sherwood In the early weeks and months of the covid-19 pandemic, it was left to patient advocates like us at Long Covid SOS to bring the issue of long term morbidity after a covid-19 infection to the notice of the UK government. Despite a series of letters to policy makers, some of which were published in The BMJ ,12 we

A ceasefire is urgently needed for the survival and safety of women and their babies, writes Soraida Hussein-Sabbah For the estimated 50 000 pregnant women trapped in Gaza, the right to give birth in a safe place with appropriate healthcare has become a distant dream.1 Only a permanent ceasefire will ensure they can seek and receive the medical care they need in safety. Gaza has many doctors, nurses

Nigel Stott’s academic and clinical contributions were built on the principle that improving health requires achieving a deep understanding of, and engagement with, complexity. His formative early life experiences began in the Valley of a Thousand Hills in KwaZulu-Natal, South Africa. Nigel’s father, Halley H Stott, founded the Valley Trust, a non-governmental organisation that understood that a curative-only

This image shows widespread asymptomatic, soft, raised papules over the oral mucosa and lips of a 9 year old girl (fig 1). The papules had been present from early childhood and became more prominent when she consumed citrus and spicy …

Despite data from 20 000 cases of postpartum depression and three times that number of controls, a meta-analysis of genetic association studies fails to identify a single-nucleotide polymorphism of genome-wide significance. This is something of a puzzle because twin studies have suggested that the condition has a heritability of more than 50%. The investigators say that larger studies are needed (

Physician associates seem to be everywhere at the moment, from government briefings to anonymous social media accounts and even parliament. Here’s the lowdown on the role, its history, and current controversies The role originated at Duke University, North Carolina, as a response to a shortage of primary care physicians in the 1960s.1 The first graduating class included Navy Hospital Corpsmen, who

Through earthquakes and civil war, the doctors and staff of the Ain Al Bayda Hospital are going above and beyond—even as a funding crisis threatens to shut them down Ghufran, a 22 year old midwife, works a 9 am to 4 pm shift in an antenatal clinic at the Ain Al Bayda Hospital in northwest Syria. She’s responsible for monthly check-ups on patients who live in one of the 58 neighbouring camps for internally

A 4 year old boy was brought to the paediatric dermatology department by his parents because they had noticed a small light brown spot on his left palm, which had been growing progressively over the past year. The child had been seen previously by a dermatologist, who suspected melanoma and referred him. The lesion had shown no signs of prior inflammation or trauma. Apart from palm hyperhidrosis (excessive

Health leaders must take action to prevent contagion The world has faced a shortage of medical workforce for decades.1 Failure to tackle problems of recruitment and retention, accelerated by the covid-19 pandemic, is now manifesting in the closure of urgent and emergency services, and even whole hospitals, across high income countries. Closures and mergers of rural and remote hospitals are nothing

As we approach the close of 2023, a hard, unforgiving year, consider this: the world, as we know it, is about to end. Life on Earth may not survive into the 22nd century; humanity has no more than 30 years. The window of opportunity to prevent both those extinction events is less than eight years, says doctor and climate activist Hugh Montgomery (youtube.com/watch?v=i2a-6KCAuKs).1 However, hope is

Abstract not available

Abstract not available

Background Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. Methods PROSPECT

While at medical school, the calendar’s 11th month—the year’s 11th hour—seems to be inseparable from the twilight treks from hospital to home. When you awake in the dark and leave and return home in the dark, daylight is a rare and precious currency—and the holidays are too far away yet to get excited about. Although I studied in the northwest of England, after a childhood spent in one of the top most

Objective To assess the clinical and cost effectiveness of conservative management compared with laparoscopic cholecystectomy for the prevention of symptoms and complications in adults with uncomplicated symptomatic gallstone disease. Design Parallel group, pragmatic randomised, superiority trial. Setting 20 secondary care centres in the UK. Participants 434 adults (>18 years) with uncomplicated symptomatic

Good Medical Practice is a guide produced by the General Medical Council (GMC) that sets out the standards expected of doctors. A new version, coming into force next month, contains some substantial changes.1 The first is that, in anticipation of the GMC’s suggested future role as regulator of physician associates and anaesthetic associates, the guidance is no longer aimed solely at doctors—indeed

As the Universal Declaration of Human Rights turns 75 this month, we must urgently reclaim the human rights narrative in global health and defend civic space, argue Rajat Khosla and Katri Bertram > “If access to healthcare is considered a human right, who is considered human enough to have that right?” —Paul Farmer, medical anthropologist and physician For global health, 2023 has been a particularly

We read with great dismay about the decline of life support training for doctors.1 Advanced life support training gives doctors the key skills for managing patients who are deteriorating and training in cardiopulmonary resuscitation. These skills are core lifesaving interventions that need to be in the repertoire of all doctors who might need to use them. Advanced life support courses provide the opportunity

A toxic culture of defensiveness and hostility pervades the NHS, and despite many patient safety reviews nothing has fundamentally changed, Rob Behrens tells Abi Rimmer Early on in his career as a civil servant, Rob Behrens, now the parliamentary and health service ombudsman, was sent by the UK government to South Africa, to work on the transformation from apartheid to democracy. “People in Britain

We must move away from a “one size fits all” approach Symptomatic gallstone disease (cholelithiasis) is the classic indication for elective cholecystectomy.1 In addition to relieving symptoms, cholecystectomy reduces the risk of gallstone related complications such as acute cholecystitis, cholangitis, and pancreatitis. Since the late 1980s, when the advent of laparoscopic surgery reduced postoperative

Nanna Maaløe and colleagues argue that resource challenges, unclear and outdated clinical practice guidelines, and lack of women’s perspectives lead to overdiagnosis and overtreatment of prolonged labour Prolonged labour results in considerable morbidity and mortality globally in women and children, as well as risk of caesarean section, uterine rupture, and fetal adverse events.1 In some instances

Pulmonary fibrosis develops as a consequence of failed regeneration after injury. Analyzing mechanisms of regeneration and fibrogenesis directly in human tissue has been hampered by the lack of organotypic models and analytical techniques. In this work, we coupled ex vivo cytokine and drug perturbations of human precision-cut lung slices (hPCLS) with single-cell RNA sequencing and induced a multilineage

Tobacco smoking doubles the risk of active tuberculosis (TB) and accounts for up to 20% of all active TB cases globally. How smoking promotes lung microenvironments permissive to Mycobacterium tuberculosis ( Mtb ) growth remains incompletely understood. We investigated primary bronchoalveolar lavage cells from current and never smokers by performing single-cell RNA sequencing (scRNA-seq), flow cytometry

Targeting angiotensin-converting enzyme 2 (ACE2) represents a promising and effective approach to combat not only the COVID-19 pandemic but also potential future pandemics arising from coronaviruses that depend on ACE2 for infection. Here, we report ubiquitin specific peptidase 2 (USP2) as a host-directed antiviral target; we further describe the development of MS102, an orally available USP2 inhibitor

Low back pain (LBP) is often associated with the degeneration of human intervertebral discs (IVDs). However, the pain-inducing mechanism in degenerating discs remains to be elucidated. Here, we identified a subtype of locally residing human nucleus pulposus cells (NPCs), generated by certain conditions in degenerating discs, that was associated with the onset of discogenic back pain. Single-cell transcriptomic

Candida causes an estimated half-billion cases of vulvovaginal candidiasis (VVC) every year. VVC is most commonly caused by Candida albicans , which, in this setting, triggers nonprotective neutrophil infiltration, aggressive local inflammation, and symptomatic disease. Despite its prevalence, little is known about the molecular mechanisms underpinning the immunopathology of this fungal infection.

Abstract not available

Do you want to gain insight into how a medical journal is run, get involved in creating engaging educational material, and learn how to get published? If so, then apply for The BMJ Student Clegg Scholarship We are looking for four students who are studying medicine within the UK or European Union who will spend 16 days with us, remotely, between April and May 2024. There may also be the opportunity

This editorial by Jones and colleagues ( BMJ 2021;372:n463, doi:10.1136/bmj.n463, published 10 March 2021) has been retracted following …

This paper by Pell and colleagues ( BMJ 2021;372:n254, doi:10.1136/bmj.n254, published 10 March 2021) has been retracted by the journal following discussion with the authors.1 As a result of subsequent analysis after publication, the authors identified an error in the paper that, when corrected, altered the main messages of the …

In 2017, I was drafting the first manuscript for a phase I clinical trial. I was familiar with the consolidated standards of reporting trials (Consort) for randomised parallel group trials, so I was surprised by the absence of Consort reporting guidance tailored for early phase dose finding trials. After searching top medical journals for published dose finding trials to assess how they had been reported

Since around 2000, there has been a shift in UK medical and surgical culture and guidelines towards including patients in written correspondence about their care.1 UK guidelines and standards234 state that all clinical letters between physicians should be copied to the patient they concern, apart from exceptional circumstances such as the potential for patient harm or third party data breach.23 More

Alexander Azan describes how this year’s wildfires were an urgent reminder of how primary care needs to adapt to the threat climate change poses to health and health equity As a primary care physician and climate health research fellow, I’m alarmed by how unprepared I was to counsel and care for my patients during an air quality emergency in New York City earlier this year. In June 2023, air pollution

YYNYsalazar301123.f1YY Susan Abarca Salazar, a consultant in infectious diseases who was conducting doctoral research on evaluating new diagnostics to distinguish between children with tuberculous meningitis and other central nervous system infections, has died unexpectedly. Abarca Salazar was born in Cusco, Peru, the third child of Práxides Salazar Saire and Vicente Abarca Duran, who came from rural

We, a group of medical professionals, researchers, patient representatives, and politicians, call for the UK government to commit to a reversal in the rate of prescribing of antidepressants. Over the past decade, antidepressant prescriptions have almost doubled in England, rising from 47.3 million in 2011 to 85.6 million in 2022-23. Over 8.6 million adults in England are now prescribed them annually

Transformative change is needed, says WHO The effect of climate change on human health is increasingly visible,1 and health systems will inevitably be challenged over coming decades. Healthcare professionals are also increasingly aware of our climate impact—healthcare is responsible for 4.6% of emissions globally.1 The 28th annual UN climate conference (COP28) for the first time included a “health

Young leaders are critical for research, programme design, and advocacy Women, people aged under 30, and marginalised populations, especially from low and middle income countries (LMICs), continue to face barriers to participation in global health governance systems. As a result, these voices often go unheard and are not included in decision making processes related to health. As the BMJ collection

Chronic kidney disease (CKD) represents a global public health crisis, but awareness by patients and providers is poor. Defined as persistent abnormalities in kidney structure or function for more than three months, manifested as either low glomerular filtration rate or presence of a marker of kidney damage such as albuminuria, CKD can be identified through readily available blood and urine tests.

General practitioner Mat Owen-Veale talks to Kathy Oxtoby about his love of amateur dramatics and the therapeutic value of being on stage Mat Owen-Veale has found a way of escaping from being a decision laden GP—he becomes a different person. It’s a character transformation that has happened many times over the years. A low ranking cook in the trenches during the first world war, the son of a powerful

The Royal College of Surgeons of Edinburgh (RCSEd) thanks The BMJ for raising awareness about the challenges facing international medical graduates (IMGs) seeking training in the UK.1 The NHS has long benefited from the knowledge and expertise of doctors who have qualified outside the UK, and in many instances it has provided high quality training in return. The experience can vary, however, depending