The aim of this study was to quantify variables that influence outcome after median and ulnar nerve transection injuries. The authors present a meta-analysis based on individual patient data on motor and sensory recovery after microsurgical nerve repair. From 130 studies found after literature review, 23 articles were ultimately included, giving individual data for 623 median or ulnar nerve injuries. The variables age, sex, nerve, site of injury, type of repair, use of grafts, delay between injury and repair, follow-up period, and outcome were extracted. Satisfactory motor recovery was defined as British Medical Research Council motor scale grade 4 and 5, and satisfactory sensory recovery was defined as British Medical Research Council grade 3+ and 4. For motor and sensory recovery, complete data were available for 281 and 380 nerve injuries, respectively. Motor and sensory recovery were significantly associated (Spearman r = 0.62, p < 0.001). Multivariate logistic regression analysis showed that age (40 years: odds ratio, 4.3; 95 percent confidence interval, 1.6 to 11.2), site (proximal versus distal: odds ratio, 0.46; 95 percent confidence interval, 0.20 to 1.10), and delay (per month: odds ratio, 0.94; 95 percent confidence interval, 0.90 to 0.98) were significant predictors of successful motor recovery. In ulnar nerve injuries, the chance of motor recovery was 71 percent lower than in median nerve injuries (odds ratio, 0.29; 95 percent confidence interval, 0.15 to 0.55). For sensory recovery, age (odds ratio, 27.0; 95 percent confidence interval, 9.4 to 77.6) and delay (per month: odds ratio, 0.92; 95 percent confidence interval, 0.87 to 0.98) were found to be significant predictors. In this individual patient data meta-analysis, age, site, injured nerve, and delay significantly influenced prognosis after microsurgical repair of median and ulnar nerve injuries.

Dupuytren's disease is a benign fibromatosis of the hands and fingers that leads to flexion contractures. We hypothesized that multiple genetic and environmental factors influence susceptibility to this disease and sought to identify susceptibility genes to better understand its pathogenesis. We conducted a genomewide association study of 960 Dutch persons with Dupuytren's disease and 3117 controls (the discovery set) to test for association between the disease and genetic markers. We tested the 35 single-nucleotide polymorphisms (SNPs) most strongly associated with Dupuytren's disease (P<1×10⁻⁴) in the discovery set in three additional, independent case series comprising a total of 1365 affected persons and 8445 controls from Germany, the United Kingdom, and the Netherlands. Initially, we observed a significant genomewide association between Dupuytren's disease and 8 SNPs at three loci. Tests of replication and joint analysis of all data from 2325 patients with Dupuytren's disease and 11,562 controls yielded an association with 11 SNPs from nine different loci (P<5.0×10⁻⁸). Six of these loci contain genes known to be involved in the Wnt-signaling pathway: WNT4 (rs7524102) (P=2.8×10⁻⁹; odds ratio, 1.28), SFRP4 (rs16879765) (P=5.6×10⁻³⁹; odds ratio, 1.98), WNT2 (rs4730775) (P=3.0×10⁻⁸; odds ratio, 0.83), RSPO2 (rs611744) (P=7.9×10⁻¹⁵; odds ratio, 0.75), SULF1 (rs2912522) (P=2.0×10⁻¹³; odds ratio, 0.72), and WNT7B (rs6519955) (P=3.2×10⁻³³; odds ratio, 1.54). This study implicates nine different loci involved in genetic susceptibility to Dupuytren's disease. The fact that six of these nine loci harbor genes encoding proteins in the Wnt-signaling pathway suggests that aberrations in this pathway are key to the process of fibromatosis in Dupuytren's disease.

A locus for triphalangeal thumb, variably associated with pre-axial polydactyly, was previously identified in the zone of polarizing activity regulatory sequence (ZRS), a long range limb-specific enhancer of the Sonic Hedgehog ( SHH ) gene at human chromosome 7q36.3. Here, we demonstrate that a 295T>C variant in the human ZRS , previously thought to represent a neutral polymorphism, acts as a dominant allele with reduced penetrance. We found this variant in three independently ascertained probands from southern England with triphalangeal thumb, demonstrated significant linkage of the phenotype to the variant (LOD = 4.1), and identified a shared microsatellite haplotype around the ZRS , suggesting that the probands share a common ancestor. An individual homozygous for the 295C allele presented with isolated bilateral triphalangeal thumb resembling the heterozygous phenotype, suggesting that the variant is largely dominant to the wild-type allele. As a functional test of the pathogenicity of the 295C allele, we utilized a mutated ZRS construct to demonstrate that it can drive ectopic anterior expression of a reporter gene in the developing mouse forelimb. We conclude that the 295T>C variant is in fact pathogenic and, in southern England, appears to be the most common cause of triphalangeal thumb. Depending on the dispersal of the founding mutation, it may play a wider role in the aetiology of this disorder.

The use of 18F-FDG PET–CT (PET–CT) is widespread in many cancer types compared to sarcoma. We report a large retrospective audit of PET–CT in bone and soft tissue sarcoma with varied grade in a single multi-disciplinary centre. We also sought to answer three questions. Firstly, the correlation between sarcoma sub-type and grade with 18FDG SUVmax, secondly, the practical uses of PET–CT in the clinical setting of staging (during initial diagnosis), restaging (new baseline prior to definitive intervention) and treatment response. Finally, we also attempted to evaluate the potential additional benefit of PET–CT over concurrent conventional CT and MRI. A total of 957 consecutive PET–CT scans were performed in a single supra-regional centre in 493 sarcoma patients (excluding GIST) between 2007 and 2014. We compared, PET–CT SUVmax values in relation to histology and FNCCC grading. We compared PET–CT findings relative to concurrent conventional imaging (MRI and CT) in staging, restaging and treatment responses. High-grade (II/III) bone and soft tissue sarcoma correlated with high SUVmax, especially undifferentiated pleomorphic sarcoma, leiomyosarcoma, translocation induced sarcomas (Ewing, synovial, alveolar rhabdomyosarcoma), de-differentiated liposarcoma and osteosarcoma. Lower SUVmax values were observed in sarcomas of low histological grade (grade I), and in rare subtypes of intermediate grade soft tissue sarcoma (e.g. alveolar soft part sarcoma and solitary fibrous tumour). SUVmax variation was noted in malignant peripheral nerve sheath tumours, compared to the histologically benign plexiform neurofibroma, whereas PET–CT could clearly differentiate low from high-grade chondrosarcoma. We identified added utility of PET–CT in addition to MRI and CT in high-grade sarcoma of bone and soft tissues. An estimated 21% overall potential benefit was observed for PET–CT over CT/MRI, and in particular, in ‘upstaging’ of high-grade disease (from M0 to M1) where an additional 12% of cases were deemed M1 following PET–CT. PET–CT in high-grade bone and soft tissue sarcoma can add significant benefit to routine CT/MRI staging. Further prospective and multi-centre evaluation of PET–CT is warranted to determine the actual predictive value and cost-effectiveness of PET–CT in directing clinical management of clinically complex and heterogeneous high-grade sarcomas.