Environmentally friendly splints for limb immobilisation: a systematic review.

INTRODUCTION: Climate change is estimated to be the biggest global health threat of the 21st century, and has prompted calls to move away from processes in healthcare associated with high energy consumption and greenhouse gas emission. In musculoskeletal medicine, splints are widely used for limb immobilisation. These have typically been made from single-use materials such as gypsum, although in recent years purportedly environmentally friendly splints have been designed. In this systematic review, we set out to assess the clinical effectiveness of all commercially available environmentally friendly splinting materials, including Woodcast®. METHODS: The AMED (Allied and Complementary Medicine Database), CINAHL® (Cumulative Index to Nursing and Allied Health Literature), Cochrane Central Register of Controlled Trials, Embase®, Emcare® and MEDLINE® databases were searched to identify studies assessing the clinical effectiveness of biodegradable and environmentally friendly splints prior to paper review and data extraction. Formal quantitative synthesis was not possible owing to the substantial heterogeneity in the study designs and outcome measures. RESULTS: Six papers met the inclusion criteria, all investigating one particular splint material (Woodcast®). One was a case series, two were cohort studies and three were randomised controlled trials. Primary outcome measures were heterogeneous but the environmentally friendly splints were generally equivalent to traditional splint materials. Studies were mostly at a high risk of bias. CONCLUSIONS: There is limited research assessing 'green' splints in practice although the data suggest similarity with existing materials and no substantial safety concerns. Further scrutiny of the clinical effectiveness and environmental credentials of such splints is also required.

Integrative phylogenetic, phylogeographic and morphological characterisation of the Unio crassus species complex reveals cryptic diversity with important conservation implications.

The global decline of freshwater mussels and their crucial ecological services highlight the need to understand their phylogeny, phylogeography and patterns of genetic diversity to guide conservation efforts. Such knowledge is urgently needed for Unio crassus, a highly imperilled species originally widespread throughout Europe and southwest Asia. Recent studies have resurrected several species from synonymy based on mitochondrial data, revealing U. crassus to be a complex of cryptic species. To address long-standing taxonomic uncertainties hindering effective conservation, we integrate morphometric, phylogenetic, and phylogeographic analyses to examine species diversity within the U. crassus complex across its entire range. Phylogenetic analyses were performed using cytochrome c oxidase subunit I (815 specimens from 182 populations) and, for selected specimens, whole mitogenome sequences and Anchored Hybrid Enrichment (AHE) data on âˆ¼ 600 nuclear loci. Mito-nuclear discordance was detected, consistent with mitochondrial DNA gene flow between some species during the Pliocene and Pleistocene. Fossil-calibrated phylogenies based on AHE data support a Mediterranean origin for the U. crassus complex in the Early Miocene. The results of our integrative approach support 12 species in the group: the previously recognised Unio bruguierianus, Unio carneus, Unio crassus, Unio damascensis, Unio ionicus, Unio sesirmensis, and Unio tumidiformis, and the reinstatement of five nominal taxa: Unio desectusstat. rev., Unio gontieriistat. rev., Unio mardinensisstat. rev., Unio nanusstat. rev., and Unio vicariusstat. rev. Morphometric analyses of shell contours reveal important morphospace overlaps among these species, highlighting cryptic, but geographically structured, diversity. The distribution, taxonomy, phylogeography, and conservation of each species are succinctly described.

Investigation of the safety and feasibility of AAV1/SERCA2a gene transfer in patients with chronic heart failure supported with a left ventricular assist device - the SERCA-LVAD TRIAL.

The SERCA-LVAD trial was a phase 2a trial assessing the safety and feasibility of delivering an adeno-associated vector 1 carrying the cardiac isoform of the sarcoplasmic reticulum calcium ATPase (AAV1/SERCA2a) to adult chronic heart failure patients implanted with a left ventricular assist device. The SERCA-LVAD trial was one of a program of AAV1/SERCA2a cardiac gene therapy trials including CUPID1, CUPID 2 and AGENT trials. Enroled subjects were randomised to receive a single intracoronary infusion of 1 × 1013 DNase-resistant AAV1/SERCA2a particles or a placebo solution in a double-blinded design, stratified by presence of neutralising antibodies to AAV. Elective endomyocardial biopsy was performed at 6 months unless the subject had undergone cardiac transplantation, with myocardial samples assessed for the presence of exogenous viral DNA from the treatment vector. Safety assessments including ELISPOT were serially performed. Although designed as a 24 subject trial, recruitment was stopped after five subjects had been randomised and received infusion due to the neutral result from the CUPID 2 trial. Here we describe the results from the 5 patients at 3 years follow up, which confirmed that viral DNA was delivered to the failing human heart in 2 patients receiving gene therapy with vector detectable at follow up endomyocardial biopsy or cardiac transplantation. Absolute levels of detectable transgene DNA were low, and no functional benefit was observed. There were no safety concerns in this small cohort. This trial identified some of the challenges of performing gene therapy trials in this LVAD patient cohort which may help guide future trial design.

The relationship between temperature and hip and wrist fracture incidence.

INTRODUCTION: Predicting when fracture incidence will rise assists in healthcare planning and delivery of preventative strategies. The aim of this study was to investigate the relationship between temperature and the incidence of hip and wrist fractures. METHODS: Data for adults presenting to our unit with a hip or wrist fracture over a seven and eight-year period respectively were analysed. Incidence rates were calculated and compared with meteorological records. A Poisson regression model was used to quantify the relationship between temperature and fracture rate. RESULTS: During the respective study periods, 8,380 patients presented with wrist fractures and 5,279 patients were admitted with hip fractures. All women (≥50 years: p<0.001; <50 years: p<0.001) and men aged ≥50 years (p=0.046) demonstrated an increased wrist fracture rate with reduced temperature. Men aged <50 years also had an increased wrist fracture rate with increased temperature (p<0.001).The hip fracture rate was highest in women aged ≥50 years but was not associated with temperature (p=0.22). In men aged ≥50 years, there was a significant relationship between reduced temperature and increased fracture rate (p<0.001). CONCLUSIONS: Fragility fracture of the wrist is associated with temperature. Compared with an average summer, an additional 840 procedures are performed for wrist fractures during an average winter in our trust with an additional 798 bed days taken up at a cost of £3.2 million. The winter increase seen in male hip fracture incidence requires approximately 888 surgical procedures, with 18,026 bed days, and costs £7.1 million. Hip fracture incidence in older women is not related to temperature.

Proximal humerus fracture-dislocation managed by mini-open reduction and percutaneous screw fixation.

BACKGROUND: We describe a minimally open reduction and percutaneous fixation technique for three- and four-part proximal humeral fracture-dislocations which preserves soft tissues. METHODS: Eleven consecutive patients with three-and four-part proximal humeral fracture-dislocations (eight anterior, three posterior dislocations) were treated this way. The dislocation is reduced using a mini-open deltopectoral approach with a horizontal split in subscapularis. Fracture fragments are fixed with percutaneous screws. Constant and Oxford Shoulder Score were collected prospectively. RESULTS: Mean age was 51 years (range 32-65). Mean follow-up was 36 months (range 24-72 months). At last follow-up mean Constant score was 75 (range 64-86) compared to 88 (range 85-92) for the uninjured shoulder. Mean Oxford shoulder score was 41 (range 34-46). One patient developed avascular necrosis. Screw back out was seen in three patients. These were removed under local anaesthesia. There were no screw penetrations of articular surface. One patient suffered a radial nerve neuropraxia which resolved. CONCLUSION: These results are promising and comparable to published literature with other means of fixation for this complex problem. Due to minimal soft tissue dissection the complications rate is low.

Trends in paediatric distal radius fractures: an eight-year review from a large UK trauma unit.

INTRODUCTION: This observational study investigated the incidence of distal radius fractures in children, to determine whether the rate is rising, the effect of seasonal variation on incidence and whether fracture type and rate of surgical intervention has changed, to help in determining costs for secondary care and to aid resource allocation. MATERIALS AND METHODS: All paediatric patients(n = 6529) who sustained a distal radius fracture over an eight-year period (2007-2014) were identified. Poisson regression modelling was used to identify change in trends. RESULTS: There was no change in distal radius fracture incidence, rate of surgical intervention (P = 0.36) or fracture type (P = 0.70). Overall incidence was 337 fractures per 100,000 patient/years. The highest fracture incidence was seen in older school boys (708 per 100,000 patient/years, P < 0.005). Overall fracture rate was lower in winter (P < 0.005). Incidence is highest in summer and the main variation is related to season. DISCUSSION: These data can help to predict accurately the number of children presenting to the emergency department with wrist fractures depending on the time of year.

A systematic review and meta-analysis of interval training versus moderate-intensity continuous training on body adiposity.

Interval training (including high-intensity interval training [HIIT] and sprint interval training [SIT]) is promoted in both scientific and lay media as being a superior and time-efficient method for fat loss compared with traditional moderate-intensity continuous training (MICT). We evaluated the efficacy of HIIT/SIT when directly compared with MICT for the modulation of body adiposity. Databases were searched to 31 August 2016 for studies with exercise training interventions with minimum 4-week duration. Meta-analyses were conducted for within-group and between-group comparisons for total body fat percentage (%) and fat mass (kg). To investigate heterogeneity, we conducted sensitivity and meta-regression analyses. Of the 6,074 studies netted, 31 were included. Within-group analyses demonstrated reductions in total body fat (%) (HIIT/SIT: -1.26 [95% CI: -1.80; -0.72] and MICT: -1.48 [95% CI: -1.89; -1.06]) and fat mass (kg) (HIIT/SIT: -1.38 [95% CI: -1.99; -0.77] and MICT: -0.91 [95% CI: -1.45; -0.37]). There were no differences between HIIT/SIT and MICT for any body fat outcome. Analyses comparing MICT with HIIT/SIT protocols of lower time commitment and/or energy expenditure tended to favour MICT for total body fat reduction (p = 0.09). HIIT/SIT appears to provide similar benefits to MICT for body fat reduction, although not necessarily in a more time-efficient manner. However, neither short-term HIIT/SIT nor MICT produced clinically meaningful reductions in body fat.

Exercise and ectopic fat in type 2 diabetes: A systematic review and meta-analysis.

Ectopic adipose tissue surrounding the intra-abdominal organs (visceral fat) and located in the liver, heart, pancreas and muscle, is linked to cardio-metabolic complications commonly experienced in type 2 diabetes. A systematic review and meta-analysis was performed to determine the effect of exercise on ectopic fat in adults with type 2 diabetes. Relevant databases were searched to February 2016. Included were randomised controlled studies, which implemented≥4 weeks of aerobic and/or resistance exercise and quantified ectopic fat via magnetic resonance imaging, computed tomography, proton magnetic resonance spectroscopy or muscle biopsy before and after intervention. Risk of bias and study quality was assessed using Egger's funnel plot test and modified Downs and Black checklist, respectively. Of the 10,750 studies retrieved, 24 were included involving 1383 participants. No studies were found assessing the interaction between exercise and cardiac or pancreas fat. One study assessed the effect of exercise on intramyocellular triglyceride concentration. There was a significant pooled effect size for the meta-analysis comparing exercise vs. control on visceral adiposity (ES=-0.21, 95% CI: -0.37 to -0.05; P=0.010) and a near-significant pooled effect size for liver steatosis reduction with exercise (ES=-0.28, 95% CI: -0.57 to 0.01; P=0.054). Aerobic exercise (ES=-0.23, 95% CI: -0.44 to -0.03; P=0.025) but not resistance training exercise (ES=-0.13, 95% CI: -0.37 to 0.12; P=0.307) was effective for reducing visceral fat in overweight/obese adults with type 2 diabetes. These data suggest that exercise effectively reduces visceral and perhaps liver adipose tissue and that aerobic exercise should be a key feature of exercise programs aimed at reducing visceral fat in obesity-related type 2 diabetes. Further studies are required to assess the relative efficacy of exercise modality on liver fat reduction and the effect of exercise on pancreas, heart, and intramyocellular fat in type 2 diabetes and to clarify the effect of exercise on ectopic fat independent of weight loss.

Comparison of distal radius fracture intra-articular step reduction with volar locking plates and K wires: a retrospective review of quality and maintenance of fracture reduction.

This study investigated the accuracy and maintenance of reduction of intra-articular steps achieved with closed reduction and percutaneous K wires and open reduction and a volar locking plate for the treatment of intra-articular distal radius fractures. We performed a retrospective review of 359 patients with an intra-articular fracture of their distal radius. Multivariate linear regression was undertaken to investigate the influence of multiple variables such as age, gender, initial displacement and treatment method on reduction despite differences between groups. A total of 36% of patients treated with K wires and 29% with volar locking plate had a step greater than or equal to 1 mm present on the first post-operative radiograph. A total of 23% treated with K wires and 28% with volar locking plate had a residual step of 1 mm or more on the last available radiograph. There was no difference identified between the two techniques for quality of initial reduction or persisting step on the last available radiographs. Step behaviour and further reduction of step post-operatively was similar for both treatment methods. Initial displacement and increased age influenced initial reduction. Initial fracture displacement shown radiologically was the only variable identified that influenced the persistence of a step on post-operative radiographs. LEVEL OF EVIDENCE: IV.

Risk factors for intramedullary nail breakage in proximal femoral fractures: a 10-year retrospective review.

INTRODUCTION Intramedullary nailing is a common treatment for proximal femoral fractures. Fracture of the nail is a rare but devastating complication that exposes often frail patients to complex revision surgery. We investigated which risk factors predict nail failure. METHODS We reviewed all cases of nail breakage seen over a 10-year period in a single busy trauma unit; 22 nail fractures were seen in 19 patients. Comparison was made with a group of 209 consecutive patients who underwent intramedullary fixation of a proximal femur fracture with no nail breakage over a 2-year period. RESULTS In the fractured nail group, mean age was 70.4 years (range 55-88 years).The mean time to fracture was 10 months (range 2.5-23 months). Logistical regression was used to show that low American Society of Anesthesiologists (ASA) score, subtrochanteric fracture and pathological fracture were independent risk factors for nail fracture. CONCLUSIONS Young patients with a low ASA score are at highest risk of nail breakage. We advise close follow-up of patients with these risk factors until bony union has been achieved. In addition, there may be merit in considering other treatment options, such as proximal femoral replacement, especially for those with pathological fracture with a good prognosis.

Metabolome variations in the Porphyromonas gingivalis vimA mutant during hydrogen peroxide-induced oxidative stress.

The adaptability and survival of Porphyromonas gingivalis in the oxidative microenvironment of the periodontal pocket are indispensable for survival and virulence, and are modulated by multiple systems. Among the various genes involved in P. gingivalis oxidative stress resistance, vimA gene is a part of the 6.15-kb locus. To elucidate the role of a P. gingivalis vimA-defective mutant in oxidative stress resistance, we used a global approach to assess the transcriptional profile, to study the unique metabolome variations affecting survival and virulence in an environment typical of the periodontal pocket. A multilayered protection strategy against oxidative stress was noted in P. gingivalis FLL92 with upregulation of detoxifying genes. The duration of oxidative stress was shown to differentially modulate transcription with 94 (87%) genes upregulated twofold during 10 min and 55 (83.3%) in 15 min. Most of the upregulated genes (55%), fell in the hypothetical/unknown/unassigned functional class. Metabolome variation showed reduction in fumarate and formaldehyde, hence resorting to alternative energy generation and maintenance of a reduced metabolic state. There was upregulation of transposases, genes encoding for the metal ion binding protein transport and secretion system.

WITHDRAWN: Acute effects of a high-volume resistance training session on lung function.

Ahead of Print article withdrawn by publisher.

Anthrax vaccine adsorbed: further evidence supporting continuing the vaccination series rather than restarting the series when doses are delayed.

Whether to restart or continue the series when anthrax vaccine doses are missed is a frequent medical management problem. We applied the noninferiority analysis model to this prospective study comparing the Bacillus anthracis protective antigen (PA) IgG antibody response and lethal toxin neutralization activity at day 28 to the anthrax vaccine adsorbed (AVA) (Biothrax®) administered on schedule or delayed. A total of 600 volunteers were enrolled: 354 in the on-schedule cohort; 246 in the delayed cohort. Differences were noted in immune responses between cohorts (p<0.0001) and among the racial categories (p<0.0001). Controlling for covariates, the delayed cohort was non-inferior to the on-schedule cohort for the rate of 4-fold rise in both anti-PA IgG concentration (p<0.0001) and TNA ED50 titers (p<0.0001); as well as the mean log10-transformed anti-PA IgG concentration (p<0.0001) and the mean log10-transformed TNA ED50 titers (p<0.0001). Providing a missed AVA dose after a delay as long as 5-7 years, elicits anti-PA IgG antibody and TNA ED50 responses that are robust and non-inferior to the responses observed when the 6-month dose is given on-schedule. These important data suggest it is not necessary to restart the series when doses of the anthrax vaccine are delayed as long as 5 or more years.

Fibula physeal fracture causing syndesmotic diastasis.

We report an unusual physeal fibula fracture seen in a 12 year old child. The fragment was rotated and incarcerated in the distal tibiofibular joint causing syndesmotic diastasis. The fragment required open reduction and the fibula was stabilised with k-wires. The patient made an excellent recovery.

Complications after volar locking plate fixation of distal radius fractures.

Volar locking plates are an increasingly popular treatment for distal radius fractures. We reviewed complications observed after volar locking plate fixation in a busy teaching hospital. The purpose of the study was to assess whether complication rates after volar locking plate use in general, routine trauma practice were higher than published literature from expert users. A retrospective review was carried out of patients treated with a volar locking plate between January 2009 and December 2010. The series included 206 procedures in 204 patients (77 males and 127 females) with mean age of 55 years (range 16-94). Surgery was performed by 18 different consultant surgeons and 11 registrars. A total of 22 complications were observed in 20 patients with an overall complication rate of 9.7%. Seven (3.4%) patients developed tendon problems including four (1.9%) tendon ruptures. Four (1.9%) patients required re-operation for metalwork problems; four patients developed complex regional pain syndrome (CRPS). Three fracture reduction problems were noted. A total of 16 further operations were carried out for complications. The overall complication rate was low even when surgery was done by many surgeons, suggesting that this is a safe and reproducible technique. This study provides information which can be used to counsel patients about risks, including those of tendon and metalwork problems. This allows patients to make an informed decision. Surgeons must have specific strategies to avoid these complications and remain vigilant so that these can be identified and managed early.

A systematic review and meta-analysis of the effect of aerobic vs. resistance exercise training on visceral fat.

It is increasingly recognized that the location of excess adiposity, particularly increased deposition of visceral adipose tissue (VAT), is important when determining the adverse health effects of overweight and obesity. Exercise therapy is an integral component of obesity management, but the most potent exercise prescription for VAT benefit is unclear. We aimed to evaluate the independent and synergistic effects of aerobic exercise (AEx) and progressive resistance training (PRT) and to directly compare the efficacy of AEx and PRT for beneficial VAT modulation. A systematic review and meta-analysis was performed to assess the efficacy of exercise interventions on VAT content/volume in overweight and obese adults. Relevant databases were searched to November 2010. Included studies were randomized controlled designs in which AEx or PRT in isolation or combination were employed for 4 weeks or more in adult humans, where computed tomography (CT) or magnetic resonance imaging (MRI) was used for quantification of VAT pre- and post-intervention. Of the 12196 studies from the initial search, 35 were included. After removal of outliers, there was a significant pooled effect size (ES) for the comparison between AEx therapy and control (-0.33, 95% CI: -0.52 to -0.14; P < 0.01) but not for the comparison between PRT therapy and control (0.09, 95% CI: -0.17 to -0.36; P = 0.49). Of the available nine studies which directly compared AEx with PRT, the pooled ES did not reach statistical significance (ES = 0.23, 95% CI: -0.02 to 0.50; P = 0.07 favouring AEx). The pooled ES did not reach statistical significance for interventions that combined AEx and PRT therapy vs. control (-0.28, 95% CI: -0.69 to 0.14; P = 0.19), for which only seven studies were available. These data suggest that aerobic exercise is central for exercise programmes aimed at reducing VAT, and that aerobic exercise below current recommendations for overweight/obesity management may be sufficient for beneficial VAT modification. Further investigation is needed regarding the efficacy and feasibility of multi-modal training as a means of reducing VAT.

Simulating natural selection in landscape genetics.

Linking landscape effects to key evolutionary processes through individual organism movement and natural selection is essential to provide a foundation for evolutionary landscape genetics. Of particular importance is determining how spatially-explicit, individual-based models differ from classic population genetics and evolutionary ecology models based on ideal panmictic populations in an allopatric setting in their predictions of population structure and frequency of fixation of adaptive alleles. We explore initial applications of a spatially-explicit, individual-based evolutionary landscape genetics program that incorporates all factors--mutation, gene flow, genetic drift and selection--that affect the frequency of an allele in a population. We incorporate natural selection by imposing differential survival rates defined by local relative fitness values on a landscape. Selection coefficients thus can vary not only for genotypes, but also in space as functions of local environmental variability. This simulator enables coupling of gene flow (governed by resistance surfaces), with natural selection (governed by selection surfaces). We validate the individual-based simulations under Wright-Fisher assumptions. We show that under isolation-by-distance processes, there are deviations in the rate of change and equilibrium values of allele frequency. The program provides a valuable tool (cdpop v1.0; http://cel.dbs.umt.edu/software/CDPOP/) for the study of evolutionary landscape genetics that allows explicit evaluation of the interactions between gene flow and selection in complex landscapes.

Effect of prolonged exercise and pre-exercise dietary manipulation on hepatic triglycerides in trained men.

The purpose of this study was to examine the effect of exercise and pre-exercise dietary manipulation on hepatic triglyceride concentration (HTGC). HTGC was measured by proton magnetic resonance spectroscopy ((1)H-MRS) before and after 90 min of moderate intensity cycling in six endurance trained males following 67 h of mixed diet (M) and an isocaloric minimal carbohydrate (2%) high fat (83%) diet (HF). Diets were administered by balanced crossover design. Whole-body fat oxidation, plasma-free fatty acid (FFA), glycerol and triglyceride concentrations were significantly elevated during exercise in HF versus M (P < 0.05 for all). There was no significant treatment × time interaction for HTGC (P = 0.368). However, there was a significant net increase in HTGC (time effect) during the combined 6 h exercise and post-exercise period (P = 0.037). In conclusion, we observed no measurable net change in the hepatic triglyceride pool across a period involving a prolonged exercise bout. Furthermore, manipulation of pre-exercise dietary intake did not influence the interaction between the hepatic triglyceride concentration and exercise in lean trained men. This supports the contention that hepatic triglycerides do not meaningfully contribute to the high rate of fat oxidation observed during acute exercise, or the enhancement of this with regular exercise training and/or pre-exercise dietary manipulation.

BCL2 mutations in diffuse large B-cell lymphoma.

BCL2 is deregulated in diffuse large B-cell lymphoma (DLBCL) by the t(14;18) translocation, gene amplification and/or nuclear factor-κB signaling. RNA-seq data have recently shown that BCL2 is the most highly mutated gene in germinal center B-cell (GCB) DLBCL. We have sequenced BCL2 in 298 primary DLBCL biopsies, 131 additional non-Hodgkin lymphoma biopsies, 24 DLBCL cell lines and 51 germline DNAs. We found frequent BCL2 mutations in follicular lymphoma (FL) and GCB DLBCL, but low levels of BCL2 mutations in activated B-cell DLBCL, mantle cell lymphoma, small lymphocytic leukemia and peripheral T-cell lymphoma. We found no BCL2 mutations in GC centroblasts. Many mutations were non-synonymous; they were preferentially located in the flexible loop domain, with few in BCL2-homology domains. An elevated transition/transversions ratio supports that the mutations result from somatic hypermutation. BCL2 translocations correlate with, and are likely important in acquisition of, additional BCL2 mutations in GCB DLBCL and FL. DLBCL mutations were not independently associated with survival. Although previous studies of BCL2 mutations in FL have reported mutations to result in pseudo-negative BCL2 protein expression, we find this rare in de-novo DLBCL.