A clinico-radiological review of chronic non-bacterial osteomyelitis in paediatrics, adolescents, and adults: demystifying a forgotten differential.

Chronic non-bacterial osteomyelitis (CNO), also known as non-bacterial osteitis, is a chronic autoinflammatory disease of unknown aetiology that primarily occurs in the paediatric population, although rare cases of adult-onset disease also exist. CNO has non-specific clinical and radiological presentations, and the affected population often present with bone pain of insidious onset secondary to sterile bony inflammation that can be associated with swelling, focal tenderness, and warmth at the affected sites. The pattern of bony involvement appears to be dependent on the age of onset, with adults frequently having axial skeletal lesions and children and adolescents often being affected in the appendicular skeletal sites. CNO is a diagnosis of exclusion, and imaging is heavily relied on to identify and characterise the bony lesions in addition to exclude diseases that can mimic CNO. Magnetic resonance imaging is often the reference standard with biochemical and histopathological findings being complementary. Although combining imaging methods can be used to facilitate the diagnosis, a single technique could be adequate depending on the clinical picture. Given the relatively rare incidence of CNO, limited awareness of the disease among care providers, and its similarity in clinical and radiological presentation to various bony diseases, there are often long delays in diagnosis, with adults being unfavourably affected compared to paediatrics and adolescents. This review of CNO will describe the condition, overview its clinical presentation, highlight the radiological features, and emphasise clinical pearls that can aid in diagnosis and ruling out the mimics.

Periarticular calcifications.

Periarticular calcification and ossification is a frequent finding on imaging and may sometimes pose a diagnostic challenge. The differential diagnoses for this radiological finding are wide and can be classified into broad groups such as idiopathic, developmental, trauma, burns, infection, tumor, connective tissue disease, crystalline, metabolic, vascular, and foreign bodies. With careful consideration of the clinical and imaging findings as well as awareness of mimickers of periarticular mineralization, the list of differential diagnoses can be narrowed down. This article aims to review the clinical-radiologic findings of periarticular calcified or ossified lesions with relevant imaging illustrations.

Detection of occult, undisplaced hip fractures with a dual-energy CT algorithm targeted to detection of bone marrow edema.

The purpose of this study is to describe our initial clinical experience with dual-energy computed tomography (DECT) virtual non-calcium (VNC) images for the detection of bone marrow (BM) edema in patients with suspected hip fracture following trauma. Twenty-five patients presented to the emergency department at a level 1 trauma center between January 1, 2011 and January 1, 2013 with clinical suspicion of hip fracture and normal radiographs were included. All CT scans were performed on a dual-source, dual-energy CT system. VNC images were generated using prototype software and were compared to regular bone reconstructions by two musculoskeletal radiologists in consensus. Radiological and/or clinical diagnosis of fracture at 30-day follow-up was used as the reference standard. Twenty-one patients were found to have DECT-VNC signs of bone marrow edema. Eighteen of these 21 patients were true positive and three were false positive. A concordant fracture was clearly seen on bone reconstruction images in 15 of the 18 true positive cases. In three cases, DECT-VNC was positive for bone marrow edema where bone reconstruction CT images were negative. Four patients demonstrated no DECT-VNC signs of bone marrow edema: two cases were true negative, two cases were false negative. When compared with the gold standard of hip fracture determined at retrospective follow-up, the sensitivity of DECT-VNC images of the hip was 90 %, specificity was 40 %, positive predictive value was 86 %, and negative predictive value was 50 %. Our initial experience would suggest that DECT-VNC is highly sensitive but poorly specific in the diagnosis of hip fractures in patients with normal radiographs. The value of DECT-VNC primarily lies in its ability to help detect fractures which may be subtle or undetectable on bone reconstruction CT images.

Cystinosis with sclerotic bone lesions.

A 26-year-old male with nephropathic cystinosis treated with cysteamine and renal transplantation presented for evaluation of multiple sclerotic bone lesions, which were an incidental finding on chest computerized tomography. These lesions were in a pattern consistent with osteoblastic metastases. He did not have a history of clinically significant hyperparathyroidism or cytopenias either preceding or following his transplant. Bone and tumor markers (including alkaline phosphatase and calcium) were all normal. A percutaneous bone biopsy of the lesions showed changes compatible with cystine deposition. Our case demonstrates that sclerotic bone lesions can be a feature of cystinosis in patients with normal parathyroid function and that significant bone marrow infiltration with cystine can be present even in the absence of cytopenias.

Osteoarthritis of the thumb carpometacarpal joint: correlation of ultrasound appearances to disability and treatment response.

AIM: To evaluate grading of thumb carpometacarpal joint (CMCJ) osteoarthritis (OA) using ultrasound, correlating findings with disability and treatment response. MATERIALS AND METHODS: Patients with symptomatic thumb OA attending for ultrasound-guided CMCJ steroid injection and a group of asymptomatic controls were recruited prospectively. Thumb CMCJ ultrasound was graded (osteophytes, joint-space narrowing, capsule size, and measured capsule size), and a Disabilities of the Arm Shoulder and Hand (DASH) questionnaire was completed for each patient. Symptomatic patients then underwent injection with DASH repeated 6 weeks post-treatment. Ultrasound features were correlated with the initial DASH disability score and response as defined by change in DASH 6 weeks after treatment. RESULTS: Thirty-one patients with symptomatic OA and 37 asymptomatic controls were recruited. With the exception of osteophytes (p = 0.017), no statistically significant correlation was demonstrated between severity of ultrasound features and patient disability. However, all features demonstrated statistically significant higher grades in the symptomatic group compared to controls. Ultrasound grading did not have statistical correlation with treatment response. CONCLUSION: No correlation was found between the majority of ultrasound features and the clinical severity of OA or likely response to treatment. However, these features are significantly more common in the symptomatic population.

Usage of prophylactic radiologically inserted gastrostomy in head and neck cancer patients.

AIM: To assess outcomes and usage rate of prophylactic radiologically inserted gastrostomy (RIG) in head and neck cancer (HNC) patients. MATERIALS AND METHODS: Outcome data of all HNC patients who underwent prophylactic RIG over a 22-month period (November 2007 to September 2009) in a tertiary referral centre were collected retrospectively. Thirty-day mortality, major and minor complication rates, and subsequent usage of the RIG were analysed. RESULTS: Fifty-one HNC patients underwent prophylactic RIG. Three minor and no major immediate complications were identified. Sixteen minor and three major complications at 30-days were identified. Three (5.9%) major complications were identified. There was one death due to disease progression and not RIG insertion. The RIG was not used in 17.7% of patients post-procedure. CONCLUSION: Prophylactic RIG in HNC patients has a comparable mortality rate to RIG insertion in HNC patients with mixed indications. However, the number of cases where the gastrostomy is not used raises important concerns and warrants further investigation.

Clinical outcomes following endovascular treatment of the malfunctioning autologous dialysis fistula.

BACKGROUND: There is limited long-term prospective data on the use of endovascular techniques and the use of thrombolysis in malfunctioning autologous haemodialysis fistulas. PURPOSE: Prospective assessment of clinical outcomes following angioplasty with or without low-dose thrombolysis was undertaken in patients who presented with malfunctioning autologous haemodialysis fistulas. METHODS: Consecutive patients referred to our department over a 6-month period were included. Twenty-five patients underwent percutaneous intervention by angioplasty alone (n = 14), angioplasty and stent (n = 2), thrombolysis alone (n = 2), angioplasty, thrombolysis and stent (n = 2) and angioplasty and thrombolysis (n = 5). Patients underwent clinical follow-up and were reviewed at 6, 12, 18 and 24 months to determine fistula status. Thirty-day mortality in the group was two patients. Statistical analysis was performed with Mann-Whitney, chi-squared and Kruskal-Wallis tests. Kaplan-Meier curves were constructed to compare primary and secondary patency rates. RESULTS: Technical success and initial clinical success rates were 88% and 76%, respectively. Primary and secondary clinical success rates at 6 months were 68% and 72%, at 12 months were 68% and 72%, at 18 months were 60% and 68% and at 24 months were 52% and 68%, respectively. There were no major complications following interventional procedures. There were four minor complications. After an initially successful procedure, five patients required subsequent intervention during the follow-up period. The overall fistula event rate was very low (five per 600 patient months or 0.0996 per access year) with a fistula loss rate of 0.14 per access year. CONCLUSIONS: Our results confirm that excellent clinical results can be achieved by percutaneous endovascular treatment in malfunctioning autologous fistulas, justifying their continued use as first-line management.

Experimental charge-density study on the nickel(II) coordination complex [Ni(H3L)][NO3][PF6] [H3L = N,N',N''-tris(2-hydroxy-3-methylbutyl)-1,4,7-triazacyclononane]: a reappraisal.

The experimental charge density in the title complex has been re-examined. The original work, reported some 8 years ago [Smith et al. (1997). J. Am. Chem. Soc. 119, 5028-5034], was undertaken using a very early version of the XD software, which contained serious programming errors. A re-refinement, using the original data and a recent version of the XD software, shows that many of the unusual aspects of this earlier study are artefacts due to these programming errors. The topological properties of the newly obtained experimental density compare well with those calculated from a theoretical DFT (density-functional theory) UHF-SCF (unrestricted Hartree Fock-self-consistent field) density. This report corrects several erroneous conclusions regarding the charge density in the title complex--in particular, the highly unusual diffuse Laplacian distribution about the Ni atom, and the trifurcated bond path from the Ni atom to the alcohol oxygen donor atoms are no longer observed. An examination of a range of topological properties of the metal-ligand bonds leads to the conclusion that the Ni-N and Ni-O bonds have an intermediate character, with a significant shared interaction, but with a substantial ionic component. This new study also reveals a previously unrecognized intramolecular H...H interaction in the macrocyclic ligand.

Charge densities from high-resolution synchrotron X-ray diffraction experiments.

The combination of intense X-ray sources, especially synchrotron radiation, with area-detector technology has accomplished an enormous advance in the experimental conditions available for charge-density analysis by single-crystal high-resolution X-ray diffraction. Such experiments can now be carried out in a time measured in hours rather than weeks. Some features of these experiments are examined and preliminary results are reported for charge-density studies of 2-hydroxy-5-nitrobenzaldehyde N-cyclohexylimine (1), octakis(m-tolylthio)naphthalene (2), and 7-fluoro-4-styrylcoumarin (3). Weak interactions in crystals of (1) and (3) are found to have similar charge-density characteristics. Cages in the crystal lattice of (2) have a complex charge distribution.

To breed or not to breed: an analysis of the social and density-dependent constraints on the fecundity of female badgers (Meles meles).

Data from post-mortem examinations, population density estimates and long term capture-mark-recapture studies have been combined to look at the pattern of reproductive behaviour and the social factors leading to reproductive failure in badgers in Britain. The results are used to evaluate whether the hypothesis that the defence of oestrous females (as opposed to defence of food resources) best explains territorial behaviour and the social organization of badgers. Badgers in Britain have two peaks of reproductive activity, one immediately post partum and one in the summer/autumn. These coincide with two peaks of ovulation, and in the late winter/spring there is a steep rise in the number of sows carrying blastocysts, to reach an asymptote in June for yearling sows and April in older sows. Measured by their contribution to overall productivity, winter/spring matings were much more important than summer/autumn matings, contributing 65% of total autumn blastocysts in yearling sows and 71% of autumn blastocysts in older sows. The relative importance of the two mating periods is reflected in the seasonal pattern of bite wounding in adult male badgers; minor bite wounding in January-March was 2.3 times as frequent as in August-October, and moderate-extensive bite wounding was 3.1 times more frequent. In the populations studied, pre- and post-natal losses were high, with reproductive failure occurring at all stages of the breeding cycle, so that less than 30% of potential productivity was achieved. Indeed 22% of sows failed to develop blastocysts; these had a lower body mass, less body fat, larger adrenal glands, poorer health and higher bite wound scores than sows with blastocysts. Only 44% of adult sows implanted their blastocysts and proceeded to the end of pregnancy. However, it was less easy to identify features characteristic of sows that did or did not go on to implant their blastocysts. Finally, 35% of sows that produced cubs ceased lactation early, and this loss of entire litters was thought to be due to infanticide by dominant sows. The presence of annexe setts correlates with increased productivity in younger sows, and this is thought to be because annexe setts enable younger sows and their cubs to avoid the aggression of older, more dominant sows. Living in large social groups has no net reproductive gain for adult males or females, and there was a decline in productivity (per adult) with increasing group size.(ABSTRACT TRUNCATED AT 400 WORDS)

The Gram-Charlier and multipole expansions in accurate X-ray diffraction studies: can they be distinguished?

The Gram-Charlier temperature factor formalism has been applied to a set of accurate low-temperature data on bis(pyridine)(meso-tetraphenylporphinato)iron(II), and to a theoretical set of static structure factors on the hexaaquairon(II) ion. The refinements are compared with the multipole treatment for atomic asphericity due to chemical bonding. In a treatment of the experimental data in which only the iron atom asphericity is considered, the 'thermal motion' formalism is as efficient as the multipole formalism in accounting for the observations. It is slightly less efficient when applied to the static theoretical data, though model maps based on the two treatments are remarkably similar. A high-order Gram-Charlier refinement of the porphyrin data, followed by a multipole refinement of all data with the Gram-Charlier parameters initially fixed, and later varied, shows that simultaneous refinement of anharmonic and aspherical effects is possible, though the resulting separation may not be accurate. A combined Gram-Charlier multipole refinement on the static data, however, leads to non-significant thermal parameters. It is concluded that the statistical Gram-Charlier formalism is remarkably successful in representing bonding effects in the valence charge density if these are not specifically accounted for in the scattering formalism. Statistical anharmonic thermal motion formalisms should only be used for X-ray data analysis in combination with a formalism accounting for the effect of bonding on the atomic charge density.

Crystallographic and molecular-orbital studies on the geometry of antifolate drugs.

In the common dihydrofolate reductase inhibitors an amino substituent replaces the pteridine carbonyl oxygen atom of folates, with altered hydrogen-bonding properties and size. Flexibility in the amino groups could facilitate enzyme binding. Studies of cycloguanil hydrochloride by neutron diffraction show both in-plane and out-of-plane deformation of amino groups. Molecular-orbital calculations ab initio on 2,4-diamino-5-methylpyrimidinium cation confirm that the 4-amino group is readily deformable. The 2,4-diaminoquinazoline structure is reported. Atomic co-ordinates, thermal parameters, bond distances and bond angles for cycloguanil and 2,4-diaminoquinazoline have been deposited as Supplementary Publication SUP 50108 (13 pages) at the British Library Lending Division, Boston Spa. Wetherby, West Yorkshire LS23, 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.