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.

Validation of the register-based lifetime antimicrobial usage measurement for finisher batches based on comparison with recorded antimicrobial usage at farm level.

Assessing the relationship between antimicrobial usage (AMU) and antimicrobial resistance (AMR) requires the accurate and precise utilisation of register data. Therefore, validation of register-based data is essential for evaluating the quality and, subsequently, the internal validity of studies based on the data. In this study, different smoothing methods for Veterinary Medicine Statistic Program database (VetStat)-records were validated by comparing these with farm-records. Comparison between measurements included accuracy as; completeness and correctness, and precision as; a relative difference of the error, correlation with Fisher's z transformation and reliability coefficient. The most valid methods of those examined were then used in re-analyses of the abundance of AMR genes in 10 finisher batches from a previous study. Improved accuracy was found when detailed smoothing methods were applied. Although the precision also increased, the effect was not as pronounced, as the usage estimate of all smoothing methods deviated moderately compared with the farm-registrations. Applying the most valid methods to the 10 finisher batches increased estimates of statistical model fit for aminoglycosides, lincosamides, tetracyclines and decreased estimates of statistical model fit for macrolides. The estimates of statistical model fit for sulfonamides and broad-spectrum penicillins remained the same. Through refined data transformation, VetStat-records can be used to calculate a daily amount of AMU per pig reflecting the true usage accurately and moderately precisely, which is the foundation for calculating lifetime AMU.

Assessing pre- and post-zygotic barriers between North Atlantic eels (Anguilla anguilla and A. rostrata).

Elucidating barriers to gene flow is important for understanding the dynamics of speciation. Here we investigate pre- and post-zygotic mechanisms acting between the two hybridizing species of Atlantic eels: Anguilla anguilla and A. rostrata. Temporally varying hybridization was examined by analyzing 85 species-diagnostic single-nucleotide polymorphisms (SNPs; FST ⩾0.95) in eel larvae sampled in the spawning region in the Sargasso Sea in 2007 (N=92) and 2014 (N=460). We further investigated whether genotypes at these SNPs were nonrandomly distributed in post-F1 hybrids, indicating selection. Finally, we sequenced the mitochondrial ATP6 and nuclear ATP5c1 genes in 19 hybrids, identified using SNP and restriction site associated DNA (RAD) sequencing data, to test a previously proposed hypothesis of cytonuclear incompatibility leading to adenosine triphosphate (ATP) synthase dysfunction and selection against hybrids. No F1 hybrids but only later backcrosses were observed in the Sargasso Sea in 2007 and 2014. This suggests that interbreeding between the two species only occurs in some years, possibly controlled by environmental conditions at the spawning grounds, or that interbreeding has diminished through time as a result of a declining number of spawners. Moreover, potential selection was found at the nuclear and the cytonuclear levels. Nonetheless, one glass eel individual showed a mismatch, involving an American ATP6 haplotype and European ATP5c1 alleles. This contradicted the presence of cytonuclear incompatibility but may be explained by that (1) cytonuclear incompatibility is incomplete, (2) selection acts at a later life stage or (3) other genes are important for protein function. In total, the study demonstrates the utility of genomic data when examining pre- and post-zyotic barriers in natural hybrids.

The association between measurements of antimicrobial use and resistance in the faeces microbiota of finisher batches.

The objectives were to present three approaches for calculating antimicrobial (AM) use in pigs that take into account the rearing period and rearing site, and to study the association between these measurements and phenotypical resistance and abundance of resistance genes in faeces samples from 10 finisher batches. The AM use was calculated relative to the rearing period of the batches as (i) 'Finisher Unit Exposure' at unit level, (ii) 'Lifetime Exposure' at batch level and (iii) 'Herd Exposure' at herd level. A significant effect on the occurrence of tetracycline resistance measured by cultivation was identified for Lifetime Exposure for the AM class: tetracycline. Furthermore, for Lifetime Exposure for the AM classes: macrolide, broad-spectrum penicillin, sulfonamide and tetracycline use as well as Herd Unit Exposure for the AM classes: aminoglycoside, lincosamide and tetracycline use, a significant effect was observed on the occurrence of genes coding for the AM resistance classes: aminoglycoside, lincosamide, macrolide, ß-lactam, sulfonamide and tetracycline. No effect was observed for Finisher Unit Exposure. Overall, the study shows that Lifetime Exposure is an efficient measurement of AM use in finisher batches, and has a significant effect on the occurrence of resistance, measured either by cultivation or metagenomics.

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.

The effect of statin therapy on the progression of carotid artery stenosis in relation to stenosis severity.

OBJECTIVES: To examine the effect of early statin treatment on progression of arteriosclerosis in internal carotid arteries (ICA); to compare the progression of arteriosclerosis in ICA of patients treated with a statin to the progression seen in drug-naïve patients. PATIENTS AND METHODS: We performed repetitive Doppler scans of 363 carotid arteries with ICA stenosis > or =40% in 254 patients over time. Information on statin therapy and other risk factors for stroke were correlated with the annual change in degree of ICA stenosis. RESULTS: In statin-treated patients, 19% of ICA stenosis showed a progression while 74% showed a regression of stenosis. In statin-naïve patients, 63% of stenotic arteries showed a progression, while a reduction could be observed in 28%. Decrease of ICA stenosis was most accentuated in patients with a mild stenosis and was independent of serum cholesterol levels. CONCLUSION: Treatment with statins already in early stages of ICA stenosis might delay the progression and even reverse the degree of stenosis.

Evolving Practice Patterns Over Two Decades (1993-2013) in the Management of Desmoid-type Fibromatosis in British Columbia.

AIMS: Due to the rarity and varied natural history of desmoid-type fibromatosis, evidence-based treatment standards for this disease remain lacking. This study evaluated outcomes in patients with desmoid-type fibromatosis managed at a Canadian institution over two decades. MATERIALS AND METHODS: Records of 227 patients with desmoid-type fibromatosis referred from 1990 to 2013 were retrospectively reviewed to investigate management strategies including active surveillance, surgery, radiation therapy, cryoablation, and systemic therapy, including tamoxifen and chemotherapy. RESULTS: Thirty-two per cent of cases were men, median age 40 years, median tumour size 5.4 cm. Initial treatments were surgery (79%), tamoxifen (13%), radiation therapy (5.0%), chemotherapy (1.8%) and cryoablation (1.2%). Active surveillance was used upfront in 26% of cases, most after 2005. At a median follow-up of 77 months, one patient died of disease, 13 died of unrelated causes and the remainder were alive with no evidence of disease (56%), stable/responding disease (33%) or progressive disease (4%). The recurrence rate was 25% after upfront surgery. Response rates and disease control rates were 40% and 76% for active surveillance; 68% and 96% for radiation therapy; 31% and 67% for tamoxifen; and 53% and 80% for chemotherapy. On univariable analysis, factors associated with a higher recurrence after initial surgery were young age (P = 0.012), male gender (P = 0.012) and extremity location (P = 0.005). On multivariable analysis, only young age was significantly associated with recurrence risk (P = 0.010). CONCLUSIONS: Active surveillance was associated with spontaneous regression and long-term disease control consistent with other studies. Primary radiation therapy appeared to provide a similar response and disease control compared with systemic treatments and may be a viable option for patients who are not candidates for surgery or active surveillance.

Predicting effects of changed antimicrobial usage on the abundance of antimicrobial resistance genes in finisher' gut microbiomes.

It is accepted that usage of antimicrobials (AMs) in food animals causes the emergence and spread of antimicrobial resistance (AMR) in this sector, while also contributing to the burden of AMR in humans. Curbing the increasing occurrence of AMR in food animals requires in-depth knowledge of the quantitative relationship between antimicrobial usage (AMU) and AMR to achieve desired resistance reductions from interventions targeting AMU. In the observational study, the relationships between lifetime AMU in 83 finisher batches from Danish farms and the AMR gene abundances of seven antimicrobial classes in their gut microbiomes were quantified using multi-variable linear regression models. These relationships and the national lifetime AMU in pigs were included in the predictive modelling that allowed for testing of scenarios with changed lifetime AMU for finishers produced in Denmark in 2014. A total of 50 farms from the observational study were included in validating the observational study and the predictive modelling. The results from the observational study showed that the relationship was linear, and that the parenteral usage of AMs had a high effect on specific AM-classes of resistance, whereas the peroral usage had a lower but broader effect on several classes. Three different scenarios of changed lifetime AMU were simulated in the predictive modelling. When all tetracycline usage ceased, the predicted interval reductions of aminoglycoside, lincosamide and tetracycline resistance were 4-42 %, 0-8 % and 9-18 %, respectively. When the peroral tetracycline usage of the 10 % highest users was replaced with peroral macrolide usage, the tetracycline resistance fell by 1-2 % and the macrolide and MLSb resistance increased by 5-8 %. When all extended-spectrum penicillin usage was replaced with parenteral lincosamide usage, the beta-lactam resistance fell by 2-7 %, but the lincosamide usage and resistance increased by 194 % and 10-45 %, respectively. The external validation provided results within the 95 % CI of the predictive modelling outcome at national level, while the external validation at farm level was less accurate. In conclusion, interventions targeting AMU will reduce AMR abundance, though differently depending on the targeted AM-class and provided the reduction of one AM-class usage is not replaced with usage of another AM-class. Predicting several classes of AMR gene abundance simultaneously will support stakeholders when deciding on interventions targeting AMU in the finisher production to avoid adverse and unforeseen effects on the AMR abundance. This study provides a sound predictive modelling framework for further development, including the dynamics of AMU on AMR in finishers at national level.

Pentraxin 3 in primary percutaneous coronary intervention for ST elevation myocardial infarction is associated with early irreversible myocardial damage : Kinetic profile, relationship to interleukin 6 and infarct size.

BACKGROUND: The inflammatory marker long pentraxin 3 (PTX3) has been shown to be a strong predictor of 30-day and one-year mortality after acute myocardial infarction. The aim of this study was to evaluate the kinetic profile of PTX3 and its relationship with interleukin 6 (IL-6), high-sensitive C-reactive protein (hs-CRP) and infarct size. METHODS: PTX3, IL-6 and hs-CRP were measured at predefined time points, at baseline (before percutaneous coronary intervention (PCI)), at 12 and 72 hours after PCI in 161 patients with first-time ST elevation myocardial infarction (STEMI). RESULTS: PTX3 and IL-6 levels increased in the early phase, followed by a gradual decrease between 12 and 72 hours. There were statistically significant correlations between PTX3 and IL-6 in general, for all time points and for changes over time (0-72 hours). In a linear mixed model, PTX3 predicted IL-6 (p < 0.001). PTX3 is also correlated with hs-CRP in general, and at each time point post PCI, except at baseline. PTX3, IL-6 and hs-CRP were all significantly correlated with infarct size in general, and at the peak time point for maximum troponin I. In addition, there was a modest correlation between IL-6 levels at baseline and infarct size at 72 hours after PCI (ρ = 0.23, p = 0.006). CONCLUSIONS: PTX3 had a similar kinetic profile to IL-6, with an early increase and decline, and was statistically significantly correlated with markers of infarct size in STEMI patients post primary PCI. Baseline levels of IL-6 only predicted infarct size at 72 hours post PCI.

Dual energy computed tomography in tophaceous gout.

OBJECTIVE: To evaluate the potential utility of a dual energy CT (DECT) scan in assessing urate deposits among patients with tophaceous gout, and obtain computerised quantification of tophus volume in peripheral joints. METHODS: 20 consecutive patients with tophaceous gout and 10 control patients with other arthritic conditions were included. DECT scans were performed using a renal stone colour-coding protocol that specifically assessed the chemical composition of the material (ie, urate coloured in red, calcium coloured in blue). An automated volumetric assessment of DECT was used to measure the volume of urate deposits in all peripheral joint areas. RESULTS: All 20 patients with gout showed red colour-coded urate deposits on their DECT scans, whereas none of 10 controls showed urate deposits. DECT scans revealed a total of 440 areas of urate deposition in 20 patients, whereas physical examination showed 111 areas of urate deposition (mean 22 vs 6 per patient, respectively, p<0.001). Total urate volume in a given patient ranged from 0.63 cm(3) to 249.13 cm(3), with a mean of 40.20 cm(3). CONCLUSIONS: DECT scans can produce obvious colour displays for urate deposits and help to identify subclinical tophus deposits. Furthermore, tophus volume can be measured by DECT scans through an automated volume estimation procedure.

CT-guided bone biopsy: Initial experience with a commercially available hand held Black and Decker drill.

PURPOSE: To describe the use of a simple commercially available Black and Decker hand based drill in performing CT-guided bone biopsies. MATERIALS AND METHODS: Three international institutions were enrolled in the study. In each centre, a fellowship trained musculoskeletal radiologist directed the assessment of a hand based commercial drill for performing CT-guided bone biopsies. A specially designed component was engineered which allowed the connection of a standard bone biopsy set to a commercial drill. The component was distributed to the three centres involved. Over a 3-year period, data from all three institutions was collected. Information regarding technical success, diagnostic data and complication rates were all collated to assess the technical feasibility of this technique. RESULTS: In total 68 patients underwent bone biopsy using a hand held commercial drill. Technical success was achieved in 65 patients. Diagnostic material was obtained in 53 patients. Non-diagnostic material was obtained in 12 patients. Five out of the 12 patients with non-diagnostic material had repeat biopsies with diagnostic material obtained in 2 of these. No major complications occurred in any patient. CONCLUSION: CT-guided bone biopsy using a hand held commercial drill has a technically high success rate with minimal complications.

The imaging features of gastrointestinal stromal tumours.

Gastrointestinal stromal tumours (GISTs) are a rare group of mesenchymal neoplasms that occur predominantly in the gastrointestinal tract. Previously GISTs were classified as smooth muscle tumours referred to as leiomyomas, leiomyosacromas or leiomyoblastomas. However, with the advent of immunohistochemistry, GISTs are now defined by the identification of cKit positivity. This is now used to select patients with metastatic disease who may respond to chemotherapeutic agents such as the tyrosine kinase inhibitor, STI-571. In this pictorial essay we have attemped to describe the range of imaging findings of GISTs that can suggest a pre-biopsy diagnosis.

The use of radiologically placed gastrostomy tubes in head and neck cancer patients receiving radiotherapy.

PURPOSE: Patients undergoing radiotherapy to the head and neck area frequently experience radiation reactions that can markedly restrict oral intake, require hospitalization, and occasionally cause treatment interruptions. The Vancouver Cancer Center (VCC) has recently employed radiologically placed gastrostomy tubes (G-tubes) in the management of this problem. A review of the patients on whom this procedure had been performed is the subject of this review. METHODS AND MATERIALS: Thirty-four patients had gastrostomy tubes inserted under radiologic guidance. This group is compared to a control group matched for age, sex, irradiated volume, and radiation dose, who did not have gastrostomy tubes. Patients with gastrostomy tubes were divided into two categories: (a) patients who had tubes inserted in anticipation of severe reactions, and (b) patients who developed severe radiation reactions necessitating nutritional support. RESULTS: The gastrostomy group consisted of 65% males with an average age of 59 years and stage range of II (12%), III (24%), and IV (65%). In both the elective group and the nonelective group, patients maintained their weight at 95 to 97% of the pretreatment weight, at follow-up of 6 weeks and 3 months. This compared with an average weight loss in the control group of 9% at 6 weeks and 12% at 3 months. The length of hospitalization was a mean of 4.9 days in the elective group and 19 days in the nonelective group. Complication were low compared to those documented in the literature, but included two tube migrations, two aspirations, and one gastrointestinal bleed. CONCLUSIONS: We believe that gastrostomy tubes contribute significantly to the management of patients with head and neck cancer, particularly in maintanence of nutrition, and they may decrease the need for hospitalization.

Self-reported prescribing of antibiotics for children with undifferentiated acute respiratory tract infections with cough.

BACKGROUND: Physicians are often called on to manage children with acute respiratory tract infections with cough when the clinical presentation may not allow a differentiation between viral and bacterial etiology. To develop guidelines for appropriate antibiotic use, it is necessary to understand the present prescribing patterns of physicians who manage children presenting with such an undifferentiated acute respiratory tract infection with cough (UARTIC). OBJECTIVES: To determine the variability of self-reported prescribing habits for antibiotics for children with UARTIC. METHODS: In this cross-sectional survey by a modified Dillman's Total Design Method, a mail-out questionnaire was administered to a random sample of 181 primary care family physicians and pediatricians (Toronto, Ontario, Canada) to assess perceptions of their own antibiotic-prescribing habit. RESULTS: Completed questionnaires were received from 136 (75%) eligible physicians; 32% reported that > 10% of their office visits were for UARTIC. For a 3-day history of UARTIC 24% reported prescribing antibiotics or antibiotics in reserve (i.e. a prescription to be filled if the patient's condition does not improve) always or most times. This increased to 45% when UARTIC had worsened in the 24 h before the office visit (P < 0.001). CONCLUSION: When a pediatric patient presented with UARTIC, antibiotics or antibiotics in reserve were prescribed in the absence of clear indicators of bacterial infection. Research- and evidence-based guidelines are needed to support rational antibiotic use for UARTIC.

Lesions of cartilage and bone around the knee.

A variety of bone and cartilage abnormalities can be demonstrated on magnetic resonance imaging (MRI), which can play an important role in the diagnosis and management of these abnormalities. Ischemic bone lesions, including medullary bone infarction, primary osteonecrosis, and the osteochondroses, can be precisely evaluated as to their anatomic locations and relationship to overlying cartilage. Osteochondritis dissecans may also be diagnosed and staged. Presence of subchondral fractures and bone contusions, which are frequently associated with ligament and meniscal injuries, can also be diagnosed and followed; these conditions may play a role in the evolution of osteoarthritis. The changes of osteoarthritis, including cartilage abnormalities, cyst formation, and loose bodies, can be evaluated; this evaluation may be important in the assessment of therapies. Stress fractures often have characteristic appearances, and MR may be used in making this diagnosis, especially when symptoms and other imaging are unclear. Diffuse marrow disorders including hemoglobinopathies and neoplasia are also well demonstrated.

Pseudopermeative skeletal lesions.

Permeative bone lesions are well known to radiologists and usually invoke a differential diagnosis that includes aggressive lesions such as round cell malignancies and infection. In contrast to permeative lesions, which demonstrate multiple small holes at the endosteal surface of the cortex secondary to a medullary process, we describe a series of 19 patients (seven with aggressive osteoporosis, eight with prior radiation therapy and four with hemangiomas) who demonstrated multiple tiny lucencies in the cortex which were superimposed on the medullary space and mimicked a permeative pattern radiographically. We termed this a pseudopermeative pattern. Recognition of a pseudopermeative pattern may allow a less sinister differential diagnosis to be considered and may avert unnecessary biopsy in many instances.

Carotid artery stenosis in patients who have undergone radiation therapy for head and neck malignancy.

Although it is established that small and medium sized arteries undergo extensive radiation damage, the effect on large vessels such as the carotid arteries is less well understood. We sought to determine if an increased severity of carotid artery stenosis is present in patients who have undergone radiotherapy for head and neck tumours. 45 patients aged 43-90 years (average 67) with head and neck malignancies treated with radiotherapy underwent colour Doppler ultrasonographic scanning of the carotid arteries. These patients were compared with a population of asymptomatic historical controls. 60% of patients demonstrated stenosis ranging from 21 to 86%. 38% of patients demonstrated a stenosis greater than or equal to 50%. Carotid artery stenosis appears to be increased in patients who have previously undergone treatment with radiotherapy to the head and neck regions compared with controls (p < 0.001). These findings suggest that radiation has an adverse effect on large vessels. Colour Doppler follow-up may be indicated for patients receiving head and neck radiation therapy.