Radiographs late in the follow up of uncomplicated distal radius fractures: are they worth it? Clinical outcome and financial implications

Fractures of the distal radius are common. Displacement can quickly lead to secondary osteoarthritis. Early follow up radiographs are subsequently paramount to facilitate for early attempts at reduction. Developing callus eventually makes this impractical. In the absence of complications we propose that radiographs may become obsolete at the later stages of follow up. We investigate whether clinical deformity, range of wrist movement and grip strength are independent of radiographs taken later than 2 weeks into the follow up of uncomplicated cases. Local cases between May 2009 and December 2011 were reviewed. Devised criteria regulated case selection. Data was collected from radiological software and occupational therapy clinical notes. Fractures were placed in short or term follow up groups dependant on whether they were imaged later than 2 weeks into follow up. T-tests compared our outcomes measures between these groups. 138 cases were included; 77 short term; 61 long term. No cases reported visible clinical deformity. There were no significant differences between grip strength or range of wrist movement for the short and long term groups. No cases required intervention for late displacement. Although complications may justify delayed imaging, our results suggest radiographs late in the follow up of uncomplicated distal radius fractures have no impact on our outcome measures. Further studies are required to confirm this. Financial regulation means any potential benefits from the removal of these unnecessary radiographs should be recognised. Established radiological follow up regimes need to be devised

The Genetic And Cell Free Dna Characteristics Of Soft Tissue Sarcomas

Soft tissue sarcomas (STSs) are a group of rare, malignant tumours with a relatively poor prognosis. Although they have been broadly classified as complex or simple based on their karyotype, only a few studies have investigated the genetic characteristics of STSs in detail. To further explore STS genomics we analysed a group of primary STSs using Illumina Next Generation Sequencing. This analysis revealed several characteristics of the analysed tumours including 1) a low single nucleotide variant and insertion/deletion mutational burden, 2) a high number of recurrent amplifications/deletions, 3) significant inter-tumoural heterogeneity regardless of histopathological classification and 4) complex genotypes in the vast majority of STSs analysed. Currently no circulating STS biomarkers exist. Short fragments of DNA termed cell free DNA (cfDNA) can be found in the bloodstream. Some cancer patient cfDNA is tumour derived (circulating tumour derived DNA / ctDNA) and in several malignancies this ctDNA appears to correlate with disease behaviour. Despite this, very few studies have investigated STS patient cfDNA/ctDNA. To address this paucity of work we next used quantitative PCR, semiconductor targeted NGS and digital droplet PCR to characterise the cfDNA/ctDNA characteristics of two groups of metastatic and non-metastatic STS patients. This analysis revealed elevated cfDNA levels in the metastatic patients, which weakly correlated with disease burden suggesting a potential diagnostic role. Overall ctDNA was also identified in 27% (non-metastatic) - 36% (metastatic) of the analysed patients suggesting either that 1) the experimental approach used was not specific enough to detect ctDNA in tumours as genetically heterogeneous as STSs, or that 2) not all STSs shed ctDNA. Moving forwards although this analysis highlights a potential role for the use of ctDNA profiling in STS patients, it has also identified several significant challenges that must be addressed before ctDNA can be proposed as a realistic source for novel biomarkers

Apparent trends in the use of femoral megaprostheses: an analysis from the National Joint Registry

Abstract Background Megaprosthetic replacement (MPR) of the femur is typically reserved for salvage or oncological reconstruction. Presently little is known about the provision of femoral MPRs performed nationally, the trends in indications for their use, and their outcomes beyond published unit-level data. Although the National Joint Registry (NJR) collects data as part of a mandatory arthroplasty audit process, MPR data entry on this platform is thought to be inconsistent. The aim of this study is to determine current trends for femoral MPR procedures as submitted to the NJR. Methods Data for all procedures submitted to the NJR using the following implants were extracted: METS (Stanmore/Stryker), MUTARS (Implantcast), Segmental (Zimmer), GMRS (Stryker) and MEGA C (LINK). Pseudoanonymized data were analyzed through the NJR’s research Data Access Portal and are reported using descriptive statistics. Results A total of 1781 procedures were identified. Submitted cases increased for primary and revision hip and knee categories over the study period, although they plateaued in recent years. MPR implants were most commonly used in revision hip arthroplasty procedures. MPR use for the management of peri-prosthetic fractures has increased and now represents the most commonly reported indication for MPR use in both hip and knee revision categories. Few centers submitted large MPR case volumes (which were noted to be lower than published unit case series, indicating NJR under-reporting), and the vast majority of centers submitting MPR cases did so in low volume. Conclusions Due to the limitations identified, reported case volumes must be interpreted with caution. An MPR-specific NJR data entry form has been developed to allow more accurate and tailored reporting of MPR procedures, to support specialist service provision, and to provide meaningful data for future research

Soft tissue sarcoma

Soft tissue sarcom

A prospective randomized control study on patient’s recall of consent after hand surgery: how much they want to know?

Informed consent implies that the person undergoing an intervention thoroughly understands its pros and cons. We conducted a randomized control trial to evaluate patients’ recall of complications after day case hand surgery and how this can be influenced by age and/or socioeconomic factors. Patients’ wishes on the extent and type of provided information were also evaluated. A total of 124 cases were recruited. Ten cases were excluded because they presented for follow up more than 2 weeks after surgery. The other patients were randomized into 2 groups: the first one (48) received only verbal information, while the second one (66) also received written information sheets. No statistically significant difference was noted in the recall between the two groups. No difference among gender, age or socioeconomic status was noted. Most patients preferred both written and verbal information. Preference for knowledge of rates of complications increased when surgery was dangerous. Our results don’t show any significant difference in patients’ recall depending on the type of consenting method. Nevertheless, we still propose that patients should receive as much information as possible before undergoing any intervention

Ischemia Is Not Required for Arteriogenesis in Zebrafish Embryos

OBJECTIVE: The role of ischemia in collateral vessel development (arteriogenesis) is a contentious issue that cannot be addressed using mammalian models. To investigate this, we developed models of arteriogenesis using the zebrafish embryo, which gains sufficient oxygenation via diffusion to prevent ischemia in response to arterial occlusion. METHODS AND RESULTS: We studied gridlock mutant embryos that suffer a permanently occluded aorta, and show that these restore aortic blood flow by collateral vessels. We phenocopied gridlock mutants by laser-induced proximal aortic occlusion in transgenic Fli1:eGFP/GATA1:dsRED embryos. Serial imaging showed these restore aortic blood flow via collateral vessels by recruitment of pre-existing endothelium in a manner similar to gridlocks. Collateral aortic blood flow in gridlock mutants was dependent upon both nitric oxide and myeloid cells. Confocal microscopy of transgenic gridlock/Fli1:eGFP mutants demonstrated no aberrant angiogenic response to the aortic occlusion. qPCR of HIF1α expression confirmed the absence of hypoxia in this model system. CONCLUSIONS: We conclude that NO and myeloid cell-dependent collateral vessel development is an evolutionarily ancient response to arterial occlusion, and is able to proceed in the absence of ischemia

Telomere maintenance in soft tissue sarcomas.

Soft tissue sarcomas (STS) are a diverse group of heterogeneous malignant tumours derived from mesenchymal tissues. Over 50 different STS subtypes are recognised by WHO, which show a wide range of different biological behaviours and prognoses. At present, clinicians managing this complex group of tumours face several challenges. This is reflected by the relatively poor outcome of patients with STSs compared with many other solid malignant tumours. These include difficulties securing accurate diagnoses, a lack of effective systemic treatments and absence of any sensitive circulating biomarkers to monitor patients throughout their treatment and follow-up. In order to progress STS's cells must evade the usual cellular proliferative checkpoints, and then activate a telomere maintenance mechanism in order to achieve replicative immortality. The purpose of this review is to provide an overview of STS genetics focusing particularly on these mechanisms. We will also highlight some of the key barriers to improving outcome for patients with STS, and hypothesise how a better understanding of these genetic characteristics may impact on future STS management

Aneurysmal bone cysts: A UK wide tumor center experience

Background and ObjectivesThis multicenter retrospective series of consecutive extra-spinal aneurysmal bone cysts aims to identify risk factors for treatment failure.MethodsAneurysmal bone cysts treated within seven collaborating centers with over 12-months follow-up were eligible for inclusion. Survival analyses were performed to identify variables associated with recurrence using log-rank tests and Cox proportional hazard regression.ResultsOne hundred and fifteen (M:F 60:55) patients were included. Median age at presentation was 13 years and median follow-up was 27 months. Seventy-five patients underwent surgical curettage and 27% of these required further intervention for recurrence. Of the 30 patients who underwent biopsy with limited percutaneous curettage as initial procedure, 47% required no further treatment. Patients under 13 years (log-rank p = 0.006, HR 2.3, p = 0.011) and those treated who had limited curettage (log-rank p = 0.001, HR 2.7, p = 0.002) had a higher risk of recurrence/persistence.ConclusionsThere is a high risk of recurrence following surgical treatment for aneurysmal bone cysts and this risk is higher in young patients. However, the cyst heals in a substantial number of patients who have a limited curettage at the time of biopsy

The Circulating Nucleic Acid Characteristics of Non-Metastatic Soft Tissue Sarcoma Patients

Soft tissue sarcomas (STS) are rare, malignant tumours with a generally poor prognosis. Our aim was to explore the potential of cell free DNA (cfDNA) and circulating tumour DNA (ctDNA) analysis to track non-metastatic STS patients undergoing attempted curative treatment. The analysed cohort (n = 29) contained multiple STS subtypes including myxofibrosarcomas, undifferentiated pleomorphic sarcomas, leiomyosarcomas, and dedifferentiated liposarcomas amongst others. Perioperative cfDNA levels trended towards being elevated in patients (p = 0.07), although did not correlate with tumour size, grade, recurrence or subtype, suggesting a limited diagnostic or prognostic role. To characterise ctDNA, an amplicon panel covering three genes commonly mutated in STSswas first trialled on serial plasma collected fromnine patients throughout follow-up. This approach only identified ctDNA in 2.5% (one in 40) of the analysed samples. Next custom-designed droplet digital PCR assays and Ion AmpliSeq™ panels were developed to track single nucleotide variants identified in patients’ STSs by whole exome sequencing (1-6 per patient). These approaches identified ctDNA in 17% of patients. Although ctDNA was identified before radiologically detectable recurrence in two cases, the absence of demonstrable ctDNA in 83% of cases highlights the need for much work before circulating nucleic acids can become a useful means to track STS patients

Circulating tumour-derived DNA in metastatic soft tissue sarcoma.

Following treatment 40% of soft tissue sarcoma (STS) patients suffer disease recurrence. In certain cancers circulating cell free DNA (cfDNA) and circulating tumour-derived DNA (ctDNA) characteristics correlate closely with disease burden, making them exciting potential sources of biomarkers. Despite this, the circulating nucleic acid characteristics of only 2 STS patients have been reported to date. To address this we used an Ion AmpliSeq™ panel custom specifically designed for STS patients to conduct a genetic characterisation of plasma cfDNA, buffy coat (germline) DNA and where available Formalin-Fixed Paraffin-Embedded (FFPE) primary STS tissue DNA in a cohort of 11 metastatic STS patients. We found that total cfDNA levels were significantly elevated in the STS patients analysed, and weakly correlated with disease burden. Using our Ion AmpliSeq™ panel we also successfully detected ctDNA in 4/11 (36%) patients analysed with a wide variety of STS subtypes and disease burdens. This evidence included the presence of cancer associated TP53 / PIK3CA mutations in 2 patients' plasma and matched primary STS tumour tissue, and in the plasma alone for 2 patients. We also identified 2 potential examples of allelic loss of heterozygosity in an additional patient's STS DNA and cfDNA. This is the largest study performed characterising STS patient cfDNA/ctDNA and confirms that the field remains an attractive potential source of novel STS biomarkers. Further work is required to investigate the circulating nucleic acid characteristics of individual STS subtypes, and the potential prognostic or therapeutic roles that cfDNA/ctDNA may hold for patients with these complex tumours