The Lancet

Rohini Mathur,Christopher T Rentsch,Caroline E Morton,William J Hulme,Anna Schultze,Brian MacKenna,Rosalind M Eggo,Krishnan Bhaskaran,Angel Y S Wong,Elizabeth J Williamson,Harriet Forbes,Kevin Wing,Helen I McDonald,Chris Bates,Seb Bacon,Alex J Walker,David Evans,Peter Inglesby,Amir Mehrkar,Helen J Curtis,Nicholas J DeVito,Richard Croker,Henry Drysdale,Jonathan Cockburn,John Parry,Frank Hester,Sam Harper,Ian J Douglas,Laurie Tomlinson,Stephen J W Evans,Richard Grieve,David Harrison,Kathy Rowan,Kamlesh Khunti,Nishi Chaturvedi,Liam Smeeth,Ben Goldacrefor the OpenSAFELY Collaborative

doi : 10.1016/S0140-6736(21)00634-6

ARTICLES| VOLUME 397, ISSUE 10286, P1711-1724, MAY 08, 2021

COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England.

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COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study

Victoria Jane Hall,Sarah Foulkes,Ayoub Saei,Nick Andrews,Blanche Oguti,Andre Charlett,Edgar Wellington,Julia Stowe,Natalie Gillson,Ana Atti,Jasmin Islam,Ioannis Karagiannis,Katie Munro,Jameel Khawam,Meera A Chand,Colin S Brown,Mary Ramsay,Jamie Lopez-Bernal,Susan Hopkinsand the SIREN Study Group

doi : 10.1016/S0140-6736(21)00790-X

ARTICLES| VOLUME 397, ISSUE 10286, P1725-1735, MAY 08, 2021

BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing.

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Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial

Lone B Enebo,Kasper K Berthelsen,Martin Kankam,Michael T Lund,Domenica M Rubino,Altynai Satylganova,David C W Lau

doi : 10.1016/S0140-6736(21)00845-X

ARTICLES| VOLUME 397, ISSUE 10286, P1736-1748, MAY 08, 2021

Cagrilintide, a long-acting amylin analogue, and semaglutide 2·4 mg, a glucagon-like peptide-1 analogue, are both being investigated as options for weight management. We aimed to determine the safety, tolerability, pharmacokinetics, and pharmacodynamics of this drug combination.

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Adrenalitis and anasarca in idiopathic multicentric Castleman's disease

Luke Y C Chen,Brian F Skinnider,Don Wilson,David C Fajgenbaum

doi : 10.1016/S0140-6736(21)00674-7

CLINICAL PICTURE| VOLUME 397, ISSUE 10286, P1749, MAY 08, 2021

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Breast cancer

Sibylle Loibl,Philip Poortmans,Monica Morrow,Carsten Denkert,Giuseppe Curigliano

doi : 10.1016/S0140-6736(20)32381-3

SEMINAR| VOLUME 397, ISSUE 10286, P1750-1769, MAY 08, 2021

Breast cancer is still the most common cancer worldwide. But the way breast cancer is viewed has changed drastically since its molecular hallmarks were extensively characterised, now including immunohistochemical markers (eg, ER, PR, HER2 [ERBB2], and proliferation marker protein Ki-67 [MKI67]), genomic markers (eg, BRCA1, BRCA2, and PIK3CA), and immunomarkers (eg, tumour-infiltrating lymphocytes and PD-L1). New biomarker combinations are the basis for increasingly complex diagnostic algorithms. Neoadjuvant combination therapy, often including targeted agents, is a standard of care (especially in HER2-positive and triple-negative breast cancer), and the basis for de-escalation of surgery in the breast and axilla and for risk-adapted post-neoadjuvant strategies. Radiotherapy remains an important cornerstone of breast cancer therapy, but de-escalation schemes have become the standard of care. ER-positive tumours are treated with 5–10 years of endocrine therapy and chemotherapy, based on an individual risk assessment. For metastatic breast cancer, standard therapy options include targeted approaches such as CDK4 and CDK6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PD-L1 immunotherapy, depending on tumour type and molecular profile. This range of treatment options reflects the complexity of breast cancer therapy today.

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New dimensions for hospital services and early detection of disease: a Review from the Lancet Commission into liver disease in the UK

Roger Williams,Charles Alessi,Graeme Alexander,Michael Allison,Richard Aspinall,Rachel L Batterham,Neeraj Bhala,Natalie Day,Anil Dhawan,Colin Drummond,James Ferguson,Graham Foster,Ian Gilmore,Raphael Goldacre,Harriet Gordon,Clive Henn,Deirdre Kelly,Alastair MacGilchrist,Roger McCorry,Neil McDougall,Zulfiquar Mirza,Kieran Moriarty,Philip Newsome,Richard Pinder,Stephen Roberts,Harry Rutter,Stephen Ryder,Marianne Samyn,Katherine Severi,Nick Sheron,Douglas Thorburn,Julia Verne,John Williams,Andrew Yeoman

doi : 10.1016/S0140-6736(20)32396-5

REVIEW| VOLUME 397, ISSUE 10286, P1770-1780, MAY 08, 2021

This Review, in addressing the unacceptably high mortality of patients with liver disease admitted to acute hospitals, reinforces the need for integrated clinical services. The masterplan described is based on regional, geographically sited liver centres, each linked to four to six surrounding district general hospitals—a pattern of care similar to that successfully introduced for stroke services. The plan includes the establishment of a lead and deputy lead clinician in each acute hospital, preferably a hepatologist or gastroenterologist with a special interest in liver disease, who will have prime responsibility for organising the care of admitted patients with liver disease on a 24/7 basis. Essential for the plan is greater access to intensive care units and high-dependency units, in line with the reconfiguration of emergency care due to the COVID-19 pandemic. This Review strongly recommends full implementation of alcohol care teams in hospitals and improved working links with acute medical services. We also endorse recommendations from paediatric liver services to improve overall survival figures by diagnosing biliary atresia earlier based on stool colour charts and better caring for patients with impaired cognitive ability and developmental mental health problems. Pilot studies of earlier diagnosis have shown encouraging progress, with 5–6% of previously undiagnosed cases of severe fibrosis or cirrhosis identified through use of a portable FibroScan in primary care. Similar approaches to the detection of early asymptomatic disease are described in accounts from the devolved nations, and the potential of digital technology in improving the value of clinical consultation and screening programmes in primary care is highlighted. The striking contribution of comorbidities, particularly obesity and diabetes (with excess alcohol consumption known to be a major factor in obesity), to mortality in COVID-19 reinforces the need for fiscal and other long delayed regulatory measures to reduce the prevalence of obesity. These measures include the food sugar levy and the introduction of the minimum unit price policy to reduce alcohol consumption. Improving public health, this Review emphasises, will not only mitigate the severity of further waves of COVID-19, but is crucial to reducing the unacceptable burden from liver disease in the UK.

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