Low-intensity pulsed ultrasound does not influence bone healing by distraction osteogenesis: a multicentre double-blind randomised control trial.

AIMS: The aim of this double-blind prospective randomised controlled trial was to assess whether low intensity pulsed ultrasound (LIPUS) accelerated or enhanced the rate of bone healing in adult patients undergoing distraction osteogenesis. PATIENTS AND METHODS: A total of 62 adult patients undergoing limb lengthening or bone transport by distraction osteogenesis were randomised to treatment with either an active (n = 32) or a placebo (n = 30) ultrasound device. A standardised corticotomy was performed in the proximal tibial metaphysis and a circular Ilizarov frame was used in all patients. The rate of distraction was also standardised. The primary outcome measure was the time to removal of the frame after adjusting for the length of distraction in days/cm for both the per protocol (PP) and the intention-to-treat (ITT) groups. The assessor was blinded to the form of treatment. A secondary outcome was to identify covariates affecting the time to removal of the frame. RESULTS: There was no difference in the time to removal of the frame between the PP (difference in favour of the control group was 10.1 days/cm, 95% confidence interval (CI) -3.2 to 23.4, p = 0.054) or ITT (difference 5.0 days/cm, 95% CI -8.2 to 18.21, p = 0.226) groups. The smoking status was the only covariate which increased the time to removal of the frame (hazard ratio 0.47, 95% CI 0.22 to 0.97, p = 0.042). CONCLUSION: LIPUS does not influence the rate of bone healing in patients who undergo distraction osteogenesis. Smoking may influence bone healing. Cite this article: Bone Joint J 2017;99-B:494-502.

Computer hexapod-assisted orthopaedic surgery provides a predictable and safe method of femoral deformity correction.

AIMS: Computer hexapod assisted orthopaedic surgery (CHAOS), is a method to achieve the intra-operative correction of long bone deformities using a hexapod external fixator before definitive internal fixation with minimally invasive stabilisation techniques. The aims of this study were to determine the reliability of this method in a consecutive case series of patients undergoing femoral deformity correction, with a minimum six-month follow-up, to assess the complications and to define the ideal group of patients for whom this treatment is appropriate. PATIENTS AND METHODS: The medical records and radiographs of all patients who underwent CHAOS for femoral deformity at our institution between 2005 and 2011 were retrospectively reviewed. Records were available for all 55 consecutive procedures undertaken in 49 patients with a mean age of 35.6 years (10.9 to 75.3) at the time of surgery. RESULTS: Patients were assessed at a mean interval of 44 months (6 to 90) following surgery. The indications were broad; the most common were vitamin D resistant rickets (n = 10), growth plate arrest (n = 6) and post-traumatic deformity (n = 20). Multi-planar correction was required in 33 cases. A single level osteotomy was performed in 43 cases. Locking plates were used to stabilise the osteotomy in 33 cases and intramedullary nails in the remainder. Complications included two nonunions, one death, one below-knee deep vein thrombosis, one deep infection and one revision procedure due to initial under-correction. There were no neurovascular injuries or incidence of compartment syndrome. CONCLUSION: This is the largest reported series of femoral deformity corrections using the CHAOS technique. This series demonstrates that precise intra-operative realignment is possible with a hexapod external fixator prior to definitive stabilisation with contemporary internal fixation. This combination allows reproducible correction of complex femoral deformity from a wide variety of diagnoses and age range with a low complication rate. Cite this article: Bone Joint J 2017;99-B:283-8.

Incidence of chronic kidney disease among people with diabetes: a systematic review of observational studies.

AIMS: The aim was to systematically review published articles that reported the incidence of chronic kidney disease among people with diabetes. METHODS: A systematic literature search was performed using MEDLINE, Embase and CINAHL databases. The titles and abstracts of all publications identified by the search were reviewed and 10 047 studies were retrieved. RESULTS: A total of 71 studies from 30 different countries with sample sizes ranging from 505 to 211 132 met the inclusion criteria. The annual incidence of microalbuminuria and albuminuria ranged from 1.3% to 3.8% for Type 1 diabetes. For Type 2 diabetes and studies combining both diabetes types, the range was from 3.8% to 12.7%, with four of six studies reporting annual rates between 7.4% and 8.6%. In studies reporting the incidence of eGFR < 60 ml/min/1.73 m2 using the Modification of Diet on Renal Disease (MDRD) equation, apart from one study which reported an annual incidence of 8.9%, the annual incidence ranged from 1.9% to 4.3%. The annual incidence of end-stage renal disease ranged from 0.04% to 1.8%. CONCLUSIONS: The annual incidence of microalbuminuria and albuminuria is ~ 2-3% in Type 1 diabetes, and ~ 8% in Type 2 diabetes or mixed diabetes type. The incidence of developing eGFR < 60 ml/min/1.73 m2 is ~ 2-4% per year. Despite the wide variation in methods and study design, within a particular category of kidney disease, there was only modest variation in incidence rates. These findings may be useful in clinical settings to help understand the risk of developing kidney disease among those with diabetes.

Sensorimotor dysfunction after limb fracture - An exploratory study.

BACKGROUND: Chronic pain is often associated with sensorimotor dysfunction but little is known about the early impact of limb fracture on sensory and motor performance. This exploratory study sought to assess these changes in patients with recent wrist and ankle fractures. A secondary aim was to determine the incidence of Complex Regional Pain Syndrome (CRPS) and its clinical features. METHODS: Fifty-three patients at a UK fracture centre underwent Quantitative Sensory Testing (QST), Motor Imagery (MI) and Body Perception Disturbance (BPD) assessments ≤5 weeks post-fracture (Time 1). Subjective evaluation of recovery and clinical examination for CRPS was conducted 5 weeks later (Time 2, 50 patients). Patient-reported outcomes of pain, psychological distress and limb function were collected at Times 1 and 2, and 6 months after T1 (Time 3, 36 patients, postal questionnaire). RESULTS: Quantitative sensory testing at Time 1 demonstrated cold and pressure-pain hyperalgesia in the fractured limb compared to the non-fractured side (p < 0.05). Imagined movements were reported as significantly more difficult to perform on the fractured side (p < 0.001). There was evidence of BPD in the fractured limb, similar to that found in CRPS. The incidence of CRPS was 9.4%; however, individual signs and symptoms of the condition were commonly present (70% reported ≥ one symptom). Only 33% of patients reported to being 'back to normal' 6 months after fracture with 34% reporting ongoing pain. CONCLUSIONS: Limb fracture is associated with changes in pain perceptions, motor planning, and disruption to body perception. Signs and symptoms of CRPS, ongoing pain and delayed recovery post-fracture are common. WHAT DOES THIS STUDY ADD?: In the immediate post-fracture period: Body perception disturbance is reported in the fractured limb. Imagined movements of the fractured limb are less vivid and associated with pain This study contributes to the incidence literature on CRPS.

Design and real-time control of a robotic system for fracture manipulation.

This paper presents the design, development and control of a new robotic system for fracture manipulation. The objective is to improve the precision, ergonomics and safety of the traditional surgical procedure to treat joint fractures. The achievements toward this direction are here reported and include the design, the real-time control architecture and the evaluation of a new robotic manipulator system. The robotic manipulator is a 6-DOF parallel robot with the struts developed as linear actuators. The control architecture is also described here. The high-level controller implements a host-target structure composed by a host computer (PC), a real-time controller, and an FPGA. A graphical user interface was designed allowing the surgeon to comfortably automate and monitor the robotic system. The real-time controller guarantees the determinism of the control algorithms adding an extra level of safety for the robotic automation. The system's positioning accuracy and repeatability have been demonstrated showing a maximum positioning RMSE of 1.18 ± 1.14mm (translations) and 1.85 ± 1.54° (rotations).

Intra-operative 3D imaging system for robot-assisted fracture manipulation.

Reduction is a crucial step in the treatment of broken bones. Achieving precise anatomical alignment of bone fragments is essential for a good fast healing process. Percutaneous techniques are associated with faster recovery time and lower infection risk. However, deducing intra-operatively the desired reduction position is quite challenging due to the currently available technology. The 2D nature of this technology (i.e. the image intensifier) doesn't provide enough information to the surgeon regarding the fracture alignment and rotation, which is actually a three-dimensional problem. This paper describes the design and development of a 3D imaging system for the intra-operative virtual reduction of joint fractures. The proposed imaging system is able to receive and segment CT scan data of the fracture, to generate the 3D models of the bone fragments, and display them on a GUI. A commercial optical tracker was included into the system to track the actual pose of the bone fragments in the physical space, and generate the corresponding pose relations in the virtual environment of the imaging system. The surgeon virtually reduces the fracture in the 3D virtual environment, and a robotic manipulator connected to the fracture through an orthopedic pin executes the physical reductions accordingly. The system is here evaluated through fracture reduction experiments, demonstrating a reduction accuracy of 1.04 ± 0.69 mm (translational RMSE) and 0.89 ± 0.71 ° (rotational RMSE).

Glycogen synthase kinase-3ß (GSK-3ß) and its dysregulation in glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most frequently occurring and devastating human brain malignancy, retaining almost universal mortality and a median survival of only 14 months, even with recent advances in multimodal treatments. Gliomas are characterised as being both highly resistant to chemo- and radiotherapy and highly invasive, rendering conventional interventions palliative. The continual dismal prognosis for GBM patients identifies an urgent need for the evolutionary development of new treatment modalities. This includes molecular targeted therapies as many signaling molecules and associated pathways have been implicated in the development and survival of malignant gliomas including the protein kinase, glycogen synthase kinase 3 beta (GSK-3ß). Here we review the activity and function of GSK-3ß in a number of signaling pathways and its role in gliomagenesis.

The University of Oklahoma College of Medicine summer medical program for high school students.

To enhance diversity of applicants to University of Oklahoma College of Medicine, a Summer Medical Program for High School Students was started in 2009. This comprehensive pipeline program included sessions on applying to medical school, interaction with a panel of minority physicians and health care professionals role models, clinically oriented didactics taught by physician faculty, shadowing experiences in clinics and hospitals, and presentation of student research reports. Students' assessments in 2009 showed increased understanding of the medical school application process, the medical curriculum and the medical field, and an increase in students'likeliness to choose a medical career. Importance of long-term mentoring and follow-up with students to sustain their medical interests is discussed.

Assessment and management of hypertension in patients with type 2 diabetes.

BACKGROUND: Hypertension is a major risk factor for adverse outcomes in type 2 diabetes and an important target for intervention. Despite this, the management of blood pressure (BP) remains suboptimal, particularly in patients at increased risk for cardiovascular and chronic kidney disease. The aim of this study was to estimate the frequency of hypertension and its management in consecutive clinic-based samples of patients with type 2 diabetes in Australian primary care. METHODS: BP levels and antihypertensive management strategies were compared in patients with type 2 diabetes recruited as part of the Developing Education on Microalbuminuria for Awareness of reNal and cardiovascular risk in Diabetes (DEMAND) study in 2003 (n = 1831) and the National Evaluation of the Frequency of Renal impairment cO-existing with Non-insulin-dependent diabetes (NEFRON) study in 2005 (n = 3893). Systolic BP levels and the use of antihypertensive therapies were examined in patients with and without chronic kidney disease. RESULTS: The patient characteristics in both studies were similar in that more than 80% of patients in both studies were hypertensive. Systolic BP targets of < or =130 mmHg were achieved in approximately half of all treated patients in both studies. However, the use of antihypertensive therapy either alone or in combination increased from 70.4% in DEMAND to 79.5% in NEFRON 2 years later (P < 0.001). Despite this, antihypertensive therapy continued to be underutilized in high-risk groups, including in those with established chronic kidney disease. CONCLUSION: The DEMAND and NEFRON studies both show that BP control is achievable in Australian general practice, with more than half of all patients seeing their general practitioners achieving a target systolic BP < or =130 mmHg. However, more needs to be done to further reduce BP levels, particularly in patients at high risk of adverse outcomes.

NICE work.

This editorial examines the influence of the National Institute for Clinical Excellence (NICE) on the conduct of orthopaedic surgery. It proffers criticism and suggests ways of improvement.

A pathogenic role for JNK signaling in experimental anti-GBM glomerulonephritis.

Activation of the c-Jun NH2-terminal kinase (JNK) signaling pathway is involved in the immune response; however, little is known of its role in immune-induced renal injury. In this study, we examine JNK signaling in the rat anti-glomerular basement membrane (GBM) disease model using CC-401, a specific JNK inhibitor. Animals were given CC-401, vehicle alone or no treatment starting before anti-GBM serum injection and continued treatment until killing. In acute disease, CC-401 blocked JNK signaling and reduced proteinuria in the first 24 h. The transient neutrophil influx seen at 3 h of disease was not affected, however. Continued CC-401 treatment suppressed glomerular and tubulointerstitial damage usually seen at 14 days. The protective effect may be due to modulation of macrophage activation, as CC-401 had no effect upon glomerular macrophage infiltration at day 14 despite the suppression of glomerular lesions and a marked reduction in renal tumor necrosis factor-alpha and inducible nitric oxide synthase messenger RNA levels. Treatment with CC-401 had no apparent effect on T cell or humoral immune responses. These studies suggest that JNK signaling promotes renal injury in acute and progressive rat anti-GBM disease. JNK inhibitors may be a novel therapeutic approach for the treatment of human glomerulonephritis.

Chronic kidney disease as a global public health problem: approaches and initiatives - a position statement from Kidney Disease Improving Global Outcomes.

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem. There is now convincing evidence that CKD can be detected using simple laboratory tests, and that treatment can prevent or delay complications of decreased kidney function, slow the progression of kidney disease, and reduce the risk of cardiovascular disease (CVD). Translating these advances to simple and applicable public health measures must be adopted as a goal worldwide. Understanding the relationship between CKD and other chronic diseases is important to developing a public health policy to improve outcomes. The 2004 Kidney Disease Improving Global Outcomes (KDIGO) Controversies Conference on 'Definition and Classification of Chronic Kidney Disease' represented an important endorsement of the Kidney Disease Outcome Quality Initiative definition and classification of CKD by the international community. The 2006 KDIGO Controversies Conference on CKD was convened to consider six major topics: (1) CKD classification, (2) CKD screening and surveillance, (3) public policy for CKD, (4) CVD and CVD risk factors as risk factors for development and progression of CKD, (5) association of CKD with chronic infections, and (6) association of CKD with cancer. This report contains the recommendations from the meeting. It has been reviewed by the conference participants and approved as position statement by the KDIGO Board of Directors. KDIGO will work in collaboration with international and national public health organizations to facilitate implementation of these recommendations.

Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice.

Diabetic nephropathy involves a renal inflammatory response induced by the diabetic milieu. Macrophages accumulate in diabetic kidneys in association with the local upregulation of monocyte chemoattractant protein-1 (MCP-1); however, the contribution of macrophages to renal injury and the importance of MCP-1 to their accrual are unclear. Therefore, we examined the progression of streptozotocin (STZ)-induced diabetic nephropathy in mice deficient in MCP-1 in order to explore the role of MCP-1-mediated macrophage accumulation in the development of diabetic kidney damage. Renal pathology was examined at 2, 8, 12 and 18 weeks after STZ treatment in MCP-1 intact (+/+) and deficient (-/-) mice with equivalent blood glucose and hemoglobin A1c levels. In MCP-1(+/+) mice, the development of diabetic nephropathy was associated with increased kidney MCP-1 production, which occurred mostly in tubules, consistent with our in vitro finding that elements of the diabetic milieu (high glucose and advanced glycation end products) directly stimulate tubular MCP-1 secretion. Diabetes of 18 weeks resulted in albuminuria and elevated plasma creatinine in MCP-1(+/+) mice, but these aspects of renal injury were largely suppressed in MCP-1(-/-) mice. Protection from nephropathy in diabetic MCP-1(-/-) mice was associated with marked reductions in glomerular and interstitial macrophage accumulation, histological damage and renal fibrosis. Diabetic MCP-1(-/-) mice also had a smaller proportion of kidney macrophages expressing markers of activation (inducible nitric oxide synthase or sialoadhesin) compared to diabetic MCP-1(+/+) mice. In conclusion, our study demonstrates that MCP-1-mediated macrophage accumulation and activation plays a critical role in the development of STZ-induced mouse diabetic nephropathy.

Evidence for TeV gamma-ray emission from a region of the galactic plane.

Gamma-ray emission from a narrow band at the galactic equator has previously been detected up to 30 GeV. We report evidence for a TeV gamma-ray signal from a region of the galactic plane by Milagro, a large-field-of-view water Cherenkov detector for extensive air showers. An excess with a significance of 4.5 standard deviations has been observed from the region of galactic longitude l E (40 degrees, 100 degrees) and latitude /b/ < 5 degrees. Under the assumption of a simple power law spectrum, with no cutoff in the EGRET-Milagro energy range, the measured integral flux is phi gamma(>3.5 TeV) = (6.4 +/- 1.4 +/- 2.1) x 10(-11) cm(-2) s(-1) sr(-1). This flux is consistent with an extrapolation of the EGRET spectrum between 1 and 30 GeV in this galactic region.

A new Mother-to-Infant Bonding Scale: links with early maternal mood.

Some mothers find it hard to relate to their new baby, and such failure may have long-term effects on the infant. This has been a neglected area of research. A new simple 8 item self-rating mother-to-infant bonding questionnaire has been designed to assess the feelings of a mother towards her new baby. A principal components and reliability analysis demonstrated an alpha score of 0.71. One hundred and sixty two women filled in the Kennerley Blues Scale, the Edinburgh Postnatal Depression Scale (EPDS) the Highs Scale and the new Mother to Infant Bonding Scale on day 3 postpartum. Twelve weeks later they were sent the EPDS and the Bonding scales again. One hundred and forty four returned all questionnaires. There was a strong correlation between the Bonding scores at 3 days and at 12 weeks (r(s)=0.54 p<0.001). Multiple regression analysis showed that those with raised Blues scores had worse, and those with raised Highs scores had better bonding at 3 days. Those with raised EPDS scores at 3 days (13 and over) had worse bonding scores in the "first few weeks" (median 4 versus 1, p = 0.028), as recalled at 12 weeks. This simple questionnaire is acceptable for use with mothers and gives significant correlations with their early mood.

Glomerulonephritis.

The term glomerulonephritis encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus and other compartments of the kidney. Studies with animal models have shown the crucial interaction between bone-marrow-derived inflammatory cells and cells intrinsic to the kidney that is both fundamental and unique to the pathogenesis of glomerulonephritis. The mechanisms of interaction between these cells and the mediators of their coordinated response to inflammation are being elucidated. Despite these pathophysiological advances, treatments for glomerulonephritis remain non-specific, hazardous, and only partly successful. Glomerulonephritis therefore remains a common cause of end-stage kidney failure worldwide. Molecule-specific approaches offer hope for more effective and safer treatments in the future.

Anatomy of pilon fractures of the distal tibia.

In a series of 126 consecutive pilon fractures, we have described anatomically explicable fragments. Fracture lines describing these fragments have revealed ten types of pilon fracture which belong to two families, sagittal and coronal. The type of fracture is dictated by the energy of injury, the direction of the force of injury and the age of the patient.

Chronic kidney disease in the general population.

End-stage kidney disease (ESKD), defined as the need for dialysis, receipt of a transplant, or death from chronic kidney failure, generally affects fewer than 1% of the population. However ESKD is the end result of chronic kidney disease (CKD), a widely prevalent but often silent condition with elevated risks of cardiovascular morbidity and mortality and a range of metabolic complications. A recently devised classification of CKD has facilitated prevalence estimates that reveal an "iceberg" of CKD in the community, of which dialysis and transplant patients are the tip. Hypertension, smoking, hypercholesterolemia, and obesity, currently among the World Health Organization's (WHO's) top 10 global health risks, are strongly associated with CKD. The factors, together with increasing diabetes prevalence and an aging population, will result in significant global increases in CKD and ESKD patients. Treatments now available effectively reduce the rate of progression of CKD and the extent of comorbid conditions and complications. The challenges are (1) to intervene effectively to reduce the excess burden of cardiovascular morbidity and mortality associated with CKD, (2) to identify those at greatest risk for ESKD and intervene effectively to prevent progression of early CKD, and (3) to ultimately introduce cost-effective primary prevention to reduce the overall burden of CKD. The vast majority of the global CKD burden will be in developing countries, and policy responses must be both practical and sustainable in these settings.