The Royal Hallamshire Hospital is a general and teaching hospital located in Sheffield, South Yorkshire, England. It is in the city's West End, facing Glossop Road and close to the main campus of University of Sheffield and the Collegiate Crescent campus of Sheffield Hallam University. The hospital is run by the Sheffield Teaching Hospitals NHS Foundation Trust.
Positron emission tomography combined with magnetic resonance imaging (PET/MR) has not yet achieved the level of adoption of PET/CT. This study aimed to harmonise PET imaging protocols across a national PET/MR network and to quantitatively assess whether PET/MR can achieve reliability comparable to PET/CT. While previous PET test-retest studies have demonstrated good repeatability, they have typically been limited to small cohorts or restricted site configurations. We conducted a multi-site harmonisation and rigorous test-retest study across the network of eight PET/MR scanners. Thirty-seven healthy older participants (65-90 years) underwent harmonised one-hour amyloid PET/MR scans using either [ ^18 F]flutemetamol or [ ^18 F]florbetaben on two occasions. Retest scans were performed under conditions of same-site repeatability or multi-site reproducibility. Harmonised acquisition and reconstruction protocols were applied, and amyloid burden was quantified on the Centiloid (CL) scale. CL values across 74 scans showed excellent test-retest agreement (ICC = 0.968), improving to 0.987 after exclusion of one attenuation correction related outlier. Mean test-retest variability was 2.58
Diabetic polyneuropathy affects up to 50% of people with diabetes mellitus. It encompasses several neuropathic syndromes, the most common being distal symmetrical polyneuropathy or ‘diabetic peripheral neuropathy’ (DPN). Risk factors for DPN include poor glycaemic control and drivers of macrovascular disease including hypertension. Strong evidence in humans and animals implicates nerve ischaemia as the cause of DPN. Despite several well-designed recent trials, no novel approved treatment with unequivocal effects on nerve function decline in DPN has emerged. Painful DPN affects about a quarter of those with diabetes, produces considerable disability and is challenging to assess and manage. First-line therapies are tricyclic antidepressants, serotonin–noradrenaline reuptake inhibitors (e.g. duloxetine) and anticonvulsants (e.g. pregabalin, gabapentin). Second-line drugs include opioids only under specialist care and capsaicin 8% patches, with more refractory cases referred for high-frequency spinal cord stimulation. Diabetic autonomic neuropathy also results in considerable morbidity, reduced quality of life and increased mortality. It can involve cardiovascular, gastrointestinal, urogenital, pupillomotor, thermoregulatory and sudomotor function. Although counselling and non-pharmacological interventions are of some use, more severely afflicted individuals require pharmacological intervention.
Cadaveric comparative study. To assess the additional superior reach achievable using the pedicled pectoralis major (PM) flap with subclavicular tunnelling and clavicle osteotomy compared with the standard supraclavicular route. Ten hemi-thoraces from fresh-frozen cadavers without prior clavipectoral surgery were dissected. Each PM flap was passed sequentially through three routes: supraclavicular, subclavicular, and mid-shaft clavicle osteotomy. Maximum superior reach from the clavicle midpoint to the ipsilateral preauricular-temporal region was measured under a standardised manual traction technique. Two observers recorded distances, and their mean value was used for analysis. Comparisons between the three routes were performed using the Friedman test and Wilcoxon signed-rank tests with Bonferroni adjustment. In this cadaveric series, mean ± SD reach was 166.6 ± 42.3 mm (supraclavicular), 195.6 ± 37.6 mm (subclavicular), and 215.4 ± 28.5 mm (clavicular osteotomy). The corresponding mean gains were + 29 mm (p = 0.006) from supraclavicular to subclavicular, + 20 mm (p = 0.004) from subclavicular to osteotomy, and + 49 mm (p = 0.002) from supraclavicular to osteotomy. Each step gave a measurable improvement in reach, all of which proved statistically significant. Subclavicular tunnelling and clavicle osteotomy significantly increased PM flap reach by 20–50 mm. While these gains are modest, they may be clinically useful in salvage situations where free tissue transfer is not feasible.
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.
BACKGROUND:D-dimer testing is widely integrated into diagnostic algorithms for venous thromboembolism (VTE). However, the lack of standardization across D-dimer assays and reporting may limit the comparability of study findings. OBJECTIVES:To summarize reporting of essential characteristics of D-dimer testing in VTE diagnostic management studies. METHODS:We systematically searched MEDLINE and Embase from January 1999 to August 2024 for VTE diagnostic management studies that evaluated diagnostic algorithms, including D-dimer testing, and followed patients for ≥ 4 weeks after VTE was excluded. The primary outcome was reporting of D-dimer assay characteristics. Secondary outcomes were reporting of patient numbers and failure rates per assay. RESULTS:Of 9670 articles screened, 58 studies were included: 36 (62%) enrolled patients with suspected pulmonary embolism, 21 (36%) with suspected deep vein thrombosis, and 1 with suspected VTE. Sample sizes ranged from 191 to 5400; follow-up was 1 to 6 months. Assay name was fully reported in 52 of 58 studies (90%), manufacturer in 49 of 58 (85%), unit magnitude in 42 of 46 (91%), and the unit type in 8/46 (17%). The detection limit was reported in 3 of 58 studies (5.2%); other analytical performance parameters were unreported. Nineteen quantitative assays were used across 19 combinations of thresholds and unit magnitudes. Of 17 studies using multiple assays, 9 reported patient numbers per assay, and 1 reported failure rate per assay. CONCLUSION:Key characteristics of D-dimer testing were inconsistently reported in VTE diagnostic management studies. While assay name, manufacturer, unit magnitude, and thresholds were often included, unit type and assay-specific data were frequently omitted. Minimum reporting standards for D-dimer testing are needed for VTE diagnostic management studies.
