Nottingham City Hospital is a large hospital located in Nottingham, England. It occupies a large 90-acre (360,000 m2) site on the ring road to the North of the city centre. It is composed of many buildings, most of which are joined together by long corridors. Buildings include a leisure club, a Maggies Centre for people with cancer, and a patient hotel. It is managed by the Nottingham University Hospitals NHS Trust.
BACKGROUND AND OBJECTIVE:BRCA1 and BRCA2 pathogenic germline variants (PGVs) are associated with higher risk of prostate cancer (PC). The IMPACT study evaluated the utility of targeted prostate-specific antigen (PSA) screening in BRCA1/BRCA2 PGV carriers. Here we report outcomes after five rounds of PSA screening in IMPACT. METHODS:Between 2005 and 2015, 3063 participants aged 40-69 yr (median 54 yr) were recruited from 65 centres in 20 countries in two cohorts: (1) BRCA1/BRCA2 PGV carriers (915 BRCA1, 901 BRCA2); and (2) age-matched noncarriers for a familial PGV (727 BRCA1 and 520 BRCA2 noncarriers). Annual PSA screening was performed, with PSA >3.0 ng/ml used as the indication for prostate biopsy. Our aim was to identify differences by PGV status in (1) the incidence of PC and of clinically significant PC (csPC; grade group ≥2) and (2) tumour stage and characteristics after five screening rounds. KEY FINDINGS AND LIMITATIONS:There was no statistically significant difference in PC incidence between BRCA1/BRCA2 PGV carriers and noncarriers. csPC incidence was significantly higher for BRCA2 PGV carriers than for noncarriers (3.1% vs 1.3%; p = 0.04). Among men with PC, the proportion of tumours with National Comprehensive Cancer Network intermediate unfavourable/high risk was higher in the BRCA1/BRCA2 PGV groups versus the corresponding group without PGVs (BRCA2: 65% vs 32%, p = 0.029; BRCA1: 56% vs 18%, p = 0.0017). There were no T4 or metastatic PC cases. Pathology after radical prostatectomy revealed tumour upgrading for 7/23 (26%) BRCA1 PGV carriers and 10/34 (26%) BRCA2 PGV carriers, with no tumour upgrading for men without PGVs. Study limitations include the biopsy compliance rate and changes in PC diagnostic pathways since 2005. CONCLUSIONS AND CLINICAL IMPLICATIONS:Annual PSA screening in BRCA2 PGV carriers confirmed a higher incidence of csPC and detection of clinically relevant tumours in comparison to noncarriers. For the first time, we confirm that PSA screening in BRCA1 PGV carriers results in early detection of NCCN IR-U/HR PC. Systematic PSA screening is recommended for BRCA2 PGV carriers and should be considered for BRCA1 PGV carriers.
Pontine warning syndrome describes recurrent, transient neurological episodes arising from pontine pathology and carries a high risk of subsequent infarction. We report the case of a 102-year-old woman who presented with repeated, stereotyped episodes of unilateral weakness and dysarthria before developing a confirmed pontine infarct. Early CT imaging was normal, and the diagnosis was established only after MRI demonstrated an acute brainstem lesion. Her clinical course reflects previously described patterns of fluctuating deficits linked to pontine perforator disease, intermittent hypoperfusion, and sensitivity to blood pressure changes. She was treated with dual antiplatelet therapy and made a complete recovery. This case highlights the importance of recognising pontine warning syndrome promptly, as early localisation guides imaging strategy, monitoring, and management.
