From guidelines to standards of care for open tibial fractures

IntroductionThe standards for the management of open fractures of the lower limb published by the British Association of Plastic, Reconstructive and Aesthetic surgeons (BAPRAS) and British Orthopaedic Association (BOA) were introduced to improve the treatment received by patients after open injury to the lower limb. These Standards were released after BAPRAS/BOA published Guidelines for the management of open tibial fractures.MethodsWe wished to determine the impact of these Standards upon the surgical management of open tibial fractures by comparing patients admitted to an orthoplastic centre in the 45 months concluding December 2009 (the Guidelines era) with those admitted during 2011 (the Standards era). Surgical procedures required during the first 30 days and 12 months after injury were determined. Cases were divided into ‘directly admitted patients’ (DAP) and ‘transferred patients’ (TP). Standards-era patients were divided further into those who had surgery exclusively at the orthoplastic centre (orthoplastic patients (OPP)) and those transferred after surgery (TASP).ResultsThe number of TP trebled in frequency in the Standards era, 25% of whom were transferred before surgery. Significantly fewer surgical procedures were required for DAP and OPP groups compared with TP (and TASP) groups in both eras (Mann–Whitney U-test, p=0.05). DAP and OPP groups during the Standards era underwent the fewest procedures, with the vast majority of cases treated with two or fewer procedures in the first 12 months (88% and 80%, respectively, compared with 61% in the Guidelines era). In the Guidelines era, 44% of TP cases and in the Standards era 39% of TP and 29% of TASP groups underwent two or fewer procedures.Approximately two-thirds of open tibial fractures managed in our orthoplastic centre were patients transferred after surgery. The greatest impact of the Standards was evident for those who underwent surgery exclusively in the orthoplastic centre, reflecting a more deliberate combined strategy.ConclusionThese findings vindicate the Standards as well as mandating reorganisation and resourcing of orthoplastic services to ensure immediate transfer and early combined surgery. By increasing the capacity to deal with time-dependent initial surgery, the surgical burden that the patient must endure, and which the service must provide, are reduced.     

Magnetic resonance imaging of wrist and finger joints in healthy subjects occasionally shows changes resembling erosions and synovitis as seen in rheumatoid arthritis

OBJECTIVE: To explore the presence of changes resembling rheumatoid arthritis erosions and synovitis in metacarpophalangeal (MCP) and wrist joints of healthy individuals on magnetic resonance imaging (MRI) and to compare the MRI findings with conventional radiographic, clinical, and biochemical findings. METHODS: Twenty-eight healthy individuals were studied. Contrast-enhanced MRI and conventional radiography of the dominant wrist and second through fifth MCP joints were performed, coupled with standard clinical assessments and biochemical analyses. MR images were evaluated according to the latest OMERACT (Outcome Measures in Rheumatology Clinical Trials) recommendations with respect to synovitis, erosions, and bone marrow edema. RESULTS: Conventional radiography revealed erosion-like changes in 1 of 224 MCP joint bones (0.4%) and in 1 of 420 wrist joint bones (0.2%). MRI depicted low-grade erosion-like changes in 5 of 224 MCP joint bones (2.2%) and in 7 of 420 wrist joint bones (1.7%), but postcontrast enhancement within the lesion was detected in only 8.3% of these. MRI depicted low-grade synovitis-like changes in 10 of 112 MCP joints (8.9%) and in 8 of 84 assessed wrist areas (9.5%), while only minimal early synovial enhancement was detected by dynamic MRI. Three subjects had elevated serum levels of C-reactive protein, and these subjects displayed 44.5% of the synovitis-like changes and 41.7% of the erosion-like changes. Bone marrow edema-like changes were not found in any joints. CONCLUSION: Changes resembling mild synovitis or small bone erosions are occasionally found in the MCP and wrist joints of healthy controls. Signs of synovitis on dynamic MRI, enhancement within bone erosion-like changes, and signs of bone marrow edema appear rarely or are absent in healthy controls. These signs may thus prove to be very specific in the distinction between arthritic and normal joints.     

Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease

The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.     

Circulating sCD36 is associated with unhealthy fat distribution and elevated circulating triglycerides in morbidly obese individuals

Background:

The recently identified circulating sCD36 has been proposed to reflect tissue CD36 expression, and is upregulated in case of obesity, insulin resistance and hepatic steatosis. The aim of this study was to explore the effect of weight loss secondary to bariatric surgery in relation to sCD36 among morbidly obese individuals. Furthermore, we investigated the levels of sCD36 in relation to obesity-related metabolic complications, low-grade inflammation and fat distribution.

Methods:

Twenty morbidly obese individuals (body mass index (BMI) 43.0±5.4 kg m⁻²) with a referral to Roux-en-Y gastric bypass were included. Anthropometric measurements and fasting blood samples were collected at a preoperative baseline visit and 3 months after surgery. sCD36 was measured by an in-house assay, whereas insulin sensitivity and the hepatic fat accumulation were estimated by the homeostasis model assessment (HOMA-%S) and liver fat percentage (LF%), respectively.

Results:

Postoperatively, BMI was reduced by 20% to 34.3±5.2 kg m⁻² (P<0.001). sCD36 was reduced by 31% (P=0.001) and improvements were observed in the amount of fat mass (P<0.001), truncal fat mass (P<0.001), circulating triglycerides (P=0.001), HOMA-%S (P=0.007), LF% (P=0.001) and the inflammatory marker high-sensitive C-reactive protein (P=0.005). sCD36 correlated with triglycerides (ρ=0.523, P=0.001) and truncal fat mass (ρ=0.357, P=0.026), and triglycerides were found to be an independent predictor of sCD36. At baseline, participants with the metabolic syndrome had a higher LF% and higher levels of the inflammatory biomarker YKL-40 (P=0.003 and P=0.014) as well as a tendency towards higher levels of sCD36.

Conclusion:

sCD36 was reduced by weight loss and associated with an unhealthy fat accumulation and circulating triglycerides, which support the proposed role of sCD36 as a biochemical marker of obesity-related metabolic complications and risks.     

Mitochondrial hexokinase II (HKII) and phosphoprotein enriched in astrocytes (PEA15) form a molecular switch governing cellular fate depending on the metabolic state

The metabolic state of a cell is a key determinant in the decision to live and proliferate or to die. Consequently, balanced energy metabolism and the regulation of apoptosis are critical for the development and maintenance of differentiated organisms. Hypoxia occurs physiologically during development or exercise and pathologically in vascular disease, tumorigenesis, and inflammation, interfering with homeostatic metabolism. Here, we show that the hypoxia-inducible factor (HIF)-1-regulated glycolytic enzyme hexokinase II (HKII) acts as a molecular switch that determines cellular fate by regulating both cytoprotection and induction of apoptosis based on the metabolic state. We provide evidence for a direct molecular interactor of HKII and show that, together with phosphoprotein enriched in astrocytes (PEA15), HKII inhibits apoptosis after hypoxia. In contrast, HKII accelerates apoptosis in the absence of PEA15 and under glucose deprivation. HKII both protects cells from death during hypoxia and functions as a sensor of glucose availability during normoxia, inducing apoptosis in response to glucose depletion. Thus, HKII-mediated apoptosis may represent an evolutionarily conserved altruistic mechanism to eliminate cells during metabolic stress to the advantage of a multicellular organism.