mRNA-4359 alone or in combination with pembrolizumab dependent on which arm the participant is assigned. mRNA-4359 dosing: mRNA-4359 will be given at the study site by injection into shoulder or thigh muscle (intramuscular [IM] injection) once every 3 weeks (Day 1 of every cycle). Up to 9 doses of mRNA-4359 will be given in this study, over an approximately 6-month period. Pembrolizumab dosing: If taking pembrolizumab in combination with mRNA-4539, pembrolizumab will be given at the study site by infusion into ...

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The primary objective is to determine whether there is a cyclical component to hypercortisolaemia in all patients diagnosed with endogenous Cushing’s syndrome. The secondary objective is to study post-operative CS patients who have features of CS recurrence and also to study patients with strong clinical suspicion for CS but no test is confirming the diagnosis. Study question in this group: how long should patients be monitored before it can be concluded that the patient does not have CS.

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Breast cancer affects one in eight women. Over 40% of women needing surgery require mastectomy and are offered breast reconstruction with an implant. Since 2015, surgeons have been using mesh to provide additional cover and support to the implant on the chest wall. Mesh costs £2500 and uncertainty exists about its benefits and risks to patients. Meshes have been reported to increase post-operative problems whereas the mesh industry reports benefits. We must discuss concerns about mesh following publicised issues with ...

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The liver plays a key role in producing the proteins involved in blood clotting (haemostasis), both proteins promoting clotting (pro-coagulants) and those preventing clotting (anti-coagulants). It also has a role in removing these proteins from the circulation. Patients with liver disease have complex changes in haemostasis, which is overall ‘rebalanced’. When patients with liver disease are sick, and admitted to hospital, this rebalanced haemostasis is thought to be more unstable. These patients are at high risk of both bleeding and ...

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A malignant pleural effusion (MPE) is a buildup of fluid around the lungs due to any type of cancer that has either started or spread to the lining of the lungs (pleura). This effects over 100 people per day in the UK and patients with MPE experience debilitating breathlessness due to fluid build up and delays in diagnosis. In the current investigation and management pathway for patients suspected MPE, patients have some fluid drawn off and analysed for cancer cells, but ...

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This is a single stage,single arm phase II,open,label,multi centre trial of patients with HER2 positive GOA who are ctDNA positive following neoadjuvant chemotherapy and surgery. HER2 positive will be defined as IHC3+ or IHC2+/ISH+ positive on diagnostic biopsy or resection specimen. ctDNA result will be determined using the Natera Signatera assay. All patients will be treated with trastuzumab deruxtecan at a dose of 6.4 mg/kg intravenously every 21 days for 6 months. If required patients may dose reduce to 5.4 ...

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The PROTECT-HF trial, funded by the British Heart Foundation, will compare two different pacing approaches for treating patients with slow heart rates. In it we will compare the standard approach for pacing, right ventricular pacing, with a new form of pacing, physiological pacing. With right ventricular pacing the pacemaker lead is positioned on the heart muscle in the right ventricle (the chamber of the heart which pumps blood to the lungs). This method is very effective at treating slow heart ...

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IELSG48 is a Phase III,interventional,multicenter,open label,randomized study to evaluate whether treatment with zanubrutinib in combination with rituximab will result in an improvement in PFS compared to treatment with rituximab in patients with previously untreated SMZL. Approximately 120 subjects will be randomized in a 1:1 ratio to receive zanubrutinib and rituximab Treatment Arm A) or rituximab (Treatment Arm B). The study will include a Screening Phase,a Treatment Phase,and a Follow-Up Phase. Subjects with investigator-confirmed progressive disease according to the Lugano 2014 criteria ...

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Follicular lymphoma is a common mature B cell malignancy with a UK incidence of 3.3/100,000 people per year1. Most patients have advanced stage disease that follows a protracted and incurable disease course leading to a high overall disease prevalence. Despite advances in front line management, treatment of relapsed and refractory (r/r) FL has not been standardised and data on treatment patterns and clinical outcomes are lacking, presenting significant challenges for therapy selection and novel drug development to optimise clinical outcomes. ...

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Clavicle (collar bone) fractures make up around 5% of all bone fractures. Usually, people fracture the middle part of their collarbone but sometimes the outer part on top of the shoulder breaks and separates. This is called a “displaced distal clavicle fracture”. These fractures can be very painful, make it hard to move your arm, disturb sleep and affect the appearance of your shoulder. Patients either undergo surgery to repair the collarbone with plates and screws or they wear a ...

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