Advances in the clinical management of uveal melanoma.

Melanomas arising in the uveal tract of the eye are a rare form of the disease with a biology and clinical phenotype distinct from their more common cutaneous counterparts. Treatment of primary uveal melanoma with radiotherapy, enucleation or other modalities achieves local control in more than 90% of patients, although 40% or more ultimately develop distant metastases, most commonly in the liver. Until January 2022, no systemic therapy had received regulatory approval for patients with metastatic uveal melanoma, and these patients have historically had a dismal prognosis owing to the limited efficacy of the available treatments. A series of seminal studies over the past two decades have identified highly prevalent early, tumour-initiating oncogenic genomic aberrations, later recurring prognostic alterations and immunological features that characterize uveal melanoma. These advances have driven the development of a number of novel emerging treatments, including tebentafusp, the first systemic therapy to achieve regulatory approval for this disease. In this Review, our multidisciplinary and international group of authors summarize the biology of uveal melanoma, management of primary disease and surveillance strategies to detect recurrent disease, and then focus on the current standard and emerging regional and systemic treatment approaches for metastatic uveal melanoma.

Small ruptured cerebral aneurysms-do they rupture on formation or not?

PURPOSE: Of patients presenting with subarachnoid haemorrhage, most are due to rupture of a small aneurysm. It has been postulated that in most cases, these aneurysms form and rupture rapidly over a short period of time of days to weeks. We evaluated the hypothesis that such aneurysms therefore should never be discoverable as a pre-existing condition on medical imaging studies. METHODS: All patients presenting with subarachnoid haemorrhage due to a small cerebral aneurysm over an 11-year period were reviewed for prior imaging studies capable of detecting small aneurysms. In the subgroup that had such imaging studies, these were reviewed for the presence or absence of the index aneurysm. RESULTS: Of 851 patients presenting with subarachnoid haemorrhage over an 11-year period, 35 had prior imaging studies capable of detecting small aneurysms. In 18 out of these 35 (51%) patients, the index aneurysm was identified as a small unruptured aneurysm on these prior studies. The median time between prior imaging and aneurysm rupture was 31 months. CONCLUSION: The theory that nearly all cases of subarachnoid haemorrhage due to small aneurysms occur as a result of aneurysm formation, and rupture over a short time period is incorrect. Our findings indicate that at least half of all subarachnoid haemorrhage cases arise from the population harbouring small aneurysms as a pre-existing condition.

Aortic valve replacement in over 70- and over 80-year olds: 5-year cohort study.

BACKGROUND: Demand for aortic valve intervention remains high, and together with the recent introduction of transcatheter aortic valve implantation, this motivates a review of surgical aortic valve replacement in elderly recipients. METHODS: Consecutive patients over 70 years of age having isolated aortic valve replacement during 2007-11 were retrospectively identified and divided into 70-79 and ≥ 80 years age groups for analyses. RESULTS: 62 octogenarians and 121 septuagenarians were eligible. Among octogenarians, a lower proportion were in Canadian Cardiovascular Society angina class 3-4 (3.2% vs. 14.0%, p = 0.022) and fewer had diabetes (11.3% vs. 24.8%, p = 0.034), but a higher proportion had infective endocarditis (6.5% vs. 0%, p = 0.012), and EuroSCORE II was higher (4.9% vs. 3.7%, p < 0.001). Despite this, operative mortality was lower in octogenarians (0% vs. 7.4%, p = 0.029), although hospital stay (11.7 vs. 8.9 days, p = 0.026) was longer. One-, 3-, and 5-year survival rates were 95.2%, 90.1%, and 75.3% for octogenarians and 89.2%, 81.7%, and 70.2% for septuagenarians (p = 0.398). Canadian Cardiovascular Society angina class 3-4 and the presence of other valvular stenosis or regurgitation were independent predictors of mortality. CONCLUSION: Octogenarians had lower operative mortality despite a higher predicted risk preoperatively. Other factors beyond age and EuroSCORE, such as frailty, may be important in deciding whether elderly patients should undergo aortic valve replacement.