Ultra-high-field MRI of postmortem human fetal wrist joints: initial experience.

BACKGROUND: This study aimed to assess the feasibility of postmortem ultra-high-field magnetic resonance imaging (UHF-MRI) to study fetal musculoskeletal anatomy and explore the contribution of variation in iodine and formaldehyde (paraformaldehyde, PFA) treatment of tissue. METHODS: Seven upper extremities from human fetuses with gestational ages of 19 to 24 weeks were included in this experimental study, approved by the Medical Research Ethics Committee. The specimens were treated with various storage (0.2-4% PFA) and staining (Lugol's solution) protocols and the wrist joint was subsequently imaged with 7.0 T UHF-MRI. Soft-tissue contrast was quantified by determining regions of interest within a chondrified carpal bone (CCB) from the proximal row, the triangular fibrocartilage (TFC), and the pronator quadratus muscle (PQM) and calculating the contrast ratios (CRs) between mean signal intensities of CCB to TFC and CCB to PQM. RESULTS: UHF-MRI showed excellent soft-tissue contrast in different musculoskeletal tissues. Increasing storage time in 4% PFA, CRs decreased, resulting in a shift from relatively hyperintense to hypointense identification of the CCB. Storage in 0.2% PFA barely influenced the CRs over time. Lugol's solution caused an increase in CRs and might have even contributed to the inversion of the CRs. CONCLUSIONS: UHF-MRI is a feasible technique to image musculoskeletal structures in fetal upper extremities and most successful after short storage in 4% PFA or prolonged storage in 0.2% PFA. The use of Lugol's solution is not detrimental on soft-tissue MRI contrast and therefore enables effectively combining UHF-MRI with contrast-enhanced micro-computed tomography using a single preparation of the specimen. RELEVANCE STATEMENT: UHF-MRI can be performed after CE-micro-CT to take advantage of both techniques. KEY POINTS: • UHF-MRI is feasible to study human fetal cartilaginous and ligamentous anatomy. • Storage in low PFA concentrations (i.e., 0.2%) improves soft-tissue contrast in UHF-MRI. • Limited preservation time in high concentrations of PFA improves soft-tissue contrast in UHF-MRI. • Prior staining with Lugol's solution does not reduce soft-tissue contrast in UHF-MRI.

The Bone Biomarker of Quantitative Chemical Shift Imaging in Patients with Type 1 Gaucher Disease Receiving Low-Dose Long-Term Enzyme Replacement Therapy.

Quantitative chemical shift imaging (QCSI) is the most sensitive imaging biomarker to assess bone marrow involvement in Gaucher disease. Widespread QCSI use is limited by test availability. Anecdotal reports describe two patients demonstrating significant improvement in fat fraction (FF) assessed by QCSI following a switch from imiglucerase to taliglucerase alfa. This analysis evaluated bone marrow involvement in adults with Type 1 Gaucher disease receiving low-dose enzyme replacement therapy (ERT) with imiglucerase and/or velaglucerase alfa. We report baseline data for 30 patients meeting eligibility criteria. Median (range) duration and dose of ERT were 18 (5-26) years and 30 (30-60) U/kg/month, respectively. Low FF scores (<0.30) were observed for seven patients (23%; 95% confidence interval, 10-42%) and were more common in females (n = 6) versus males (n = 1; p < 0.025); one female was menopausal. These baseline data demonstrate that prolonged low-dose ERT with imiglucerase or velaglucerase alfa led to an adequate bone response, assessed by QCSI, in the majority of patients. A minority of such patients with suboptimal bone response require therapeutic change. The next phase of the study will address the effect of switching to taliglucerase alfa on bone status for patients with less than optimal QCSI scores (<0.30).

[Anaphylaxis due to traumatic rupture of an echinococcal cyst]. / Anafylactische reactie door ruptuur van een echinococcuscyste.

BACKGROUND: Echinococcus granulosis tapeworms' definitive hosts are dogs who live in endemic areas. Humans are infected by petting dogs or eating infected, not propely, heated food. In multiple organs, preferably in liver and lungs, these tapeworms can form cysts which in time might cause mechanical complications. CASE DESCRIPTION: A 7 year old Syrian boy was brought to our emergency department unconsciously after a light abdominal trauma. On ultrasound and CT there was no sign of traumatic injury, but a ruptured echinococcal cyst was found in the liver. The patient developed a severe anaphylaxis, with hypotension and loss of consciousness on the spill of the echinococcal cyst. The cyst was removed surgically and the boy was treated with medication. CONCLUSION: In patients with unexplained anaphylaxis, from an echinococcus endemic area, rupture of an echinococcal cyst should be part of the differential diagnosis.

The triangular fibrocartilage complex in the human wrist: A scoping review toward uniform and clinically relevant terminology.

The aim of this scoping review was to assess the composition, terminology, and anatomy of the triangular fibrocartilage complex (TFCC) of the wrist and propose unambiguous terminology regarding the individual components. The review was conducted according to the methodological framework by Arksey and O'Malley (International Journal of Social Research Methodology, 2005, 8, 19-32). Electronic databases were searched from inception until September 1, 2021 for original anatomical studies, using MeSH terms and keywords on terminology and anatomy of TFCC components. Studies using gross dissections or macro- or microscopic histology were included. Animal studies, fetal studies and studies with unknown disease status, were excluded. A total of 24 studies were included. The articular disc, the radioulnar ligaments, the meniscus homologue and the extensor carpi ulnaris tendon (sub)sheath were unanimously classified as TFCC components. One study did not include the ulnolunate and ulnotriquetral ligaments and only one study did include the ligamentum subcruentum. The largest disagreement existed regarding the inclusion of the ulnar collateral ligament. Terminological ambiguity was seen in "triangular fibrocartilage," "triangular ligament," "igamentum subcruentum," and the "proximal and distal lamina." Anatomical ambiguity existed especially regarding the radioulnar ligaments, the ulnar attachments of the TFCC and the ulnar collateral ligament. Definitions of the individual TFCC components are redundant, ambiguous, and ill-defined and therefore subject to different interpretations. In order to preclude confusion, consensus regarding terminology is recommended. We proposed a concise definition of the healthy TFCC that can be used as a starting point for future studies and current clinical practice.

Ulnar variance and triangular fibrocartilage thickness in adolescents: a cross-sectional MRI study of healthy participants.

Skeletally immature wrists are considered at risk of injury due to increased axial loading through a relatively shorter ulna. The aim of this study was to determine whether triangular fibrocartilage thickness relates to ulnar variance and age in adolescents. The radiographs and MRIs of 24 healthy adolescents were retrospectively assessed. Four observers assessed bone age and ulnar variance on radiographs and measured triangular fibrocartilage thickness on MRIs. Median calendar and bone age was 13 years and ulnar variance was -0.7 mm. Median triangular fibrocartilage thickness was 1.4 mm, with excellent inter-observer agreement (r = 0.86). It was moderately correlated with ulnar variance (ρ = -0.46) as well as with bone age (ρ = -0.49). Both variables were statistically significant predictors in a multivariate analysis. This suggests that triangular fibrocartilage thickness changes during skeletal maturation, which might influence axial load distribution in skeletally immature wrists.

The triangular fibrocartilage complex on high-resolution 3 T MRI in healthy adolescents: the thin line between asymptomatic findings and pathology.

OBJECTIVE: The objective of the study is to provide a reference for morphology, homogeneity, and signal intensity of triangular fibrocartilage complex (TFCC) and TFCC-related MRI features in adolescents. MATERIALS AND METHODS: Prospectively collected data on asymptomatic participants aged 12-18 years, between June 2015 and November 2017, were retrospectively analyzed. A radiograph was performed in all participants to determine skeletal age and ulnar variance. A 3-T MRI followed to assess TFCC components and TFCC-related features. A standardized scoring form, based on MRI definitions used in literature on adults, was used for individual assessment of all participants by four observers. Results per item were expressed as frequencies (percentages) of observations by all observers for all participants combined (n = 92). Inter-observer agreement was determined by the unweighted Fleiss' kappa with 95% confidence intervals (95% CI). RESULTS: The cohort consisted of 23 asymptomatic adolescents (12 girls and 11 boys). Median age was 13.5 years (range 12.0-17.0). Median ulnar variance was -0.7 mm (range - 2.7-1.4). Median triangular fibrocartilage (TFC) thickness was 1.4 mm (range 0.1-2.9). Diffuse increased TFC signal intensity not reaching the articular surface was observed in 30 (33%) observations and a vertical linear increased signal intensity with TFC discontinuation in 19 (20%) observations. Discontinuation between the volar radioulnar ligament and the TFC in the sagittal plane was seen in 23 (25%) observations. The extensor carpi ulnaris was completely dislocated in 10 (11%) observations, more frequent in supinated wrists (p = 0.031). Inter-observer agreement ranged from poor to fair for scoring items on the individual TFCC components. CONCLUSION: MRI findings, whether normal variation or asymptomatic abnormality, can be observed in TFCC and TFCC-related features of asymptomatic adolescents. The rather low inter-observer agreement underscores the challenges in interpreting these small structures on MRI. This should be taken into consideration when interpreting clinical MRIs and deciding upon arthroscopy.

Interobserver Reliability in Imaging-Based Fracture Union Assessment-Two Systematic Reviews.

OBJECTIVES: (A) To investigate the specialty of observers involved in imaging-based assessment of bone fracture union in recent orthopaedic trials and (B) to provide a general overview of observer differences (in terms of interobserver reliability) in radiologic fracture union assessment that have been reported between surgeons and radiologists. DATA SOURCES: Two separate systematic reviews (A, B) of English-, German-, and French-language articles in MEDLINE and Embase databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were done, with the following time frames: (A) January 2016-August 2017 and (B) through November 2017. STUDY SELECTION: (A) Clinical trials of surgical fracture treatment evaluating radiologic (non) union. (B) Interobserver studies reporting kappa-values or intraclass correlation coefficients as reliability coefficient for radiologic fracture union assessment. Inclusion criteria for both reviews were fractures of the appendicular skeleton and the use of radiographs or computed tomography. DATA EXTRACTION: Data were independently retrieved by 2 reviewers. DATA SYNTHESIS: Descriptive statistics and percentages were reported. RESULTS: (A) Forty-eight trials were included, whereof 33 (68%) did not report the observer's specialty. Six trials (13%) reported surgeon observers only, and 6 (13%) reported radiologist observers only. The median number of observers is 1 (interquartile range, 1-2). (B) Thirty-one interobserver studies were included, whereof 11 (35%) included at least 1 surgeon and 1 radiologist. Interobserver reliability varied considerably across the various fracture types studied and outcome scale used and was often unsatisfactory (kappa or intraclass correlation coefficients of <0.7). CONCLUSIONS: In most trials providing observer's characteristics, radiologic fracture union was either rated by 1 surgeon or 1 radiologist. As interobserver reliability can be unsatisfactory, we recommend surgeons and radiologists to further intensify collaboration and trials to include at least 2 observers and associated reliability statistics.

Well-founded practice or personal preference: a comparison of established techniques for measuring ulnar variance in healthy children and adolescents.

OBJECTIVES: Ulnar variance is a clinical measure used to determine the relative difference in length between the radius and ulna. We aimed to examine consistency in ulnar variance measurements and normative data in children and adolescents using the perpendicular and the Hafner methods. METHODS: Two raters measured ulnar variance on hand radiographs of 350 healthy children. Participants' mean calendar and skeletal ages were 12.3 ± 3.6 and 12.0 ± 3.7 years, 52% were female. Raters used the perpendicular method, an adapted version of the perpendicular method (in which the distal radial articular surface is defined as a sclerotic rim) and the Hafner method, being the distance between the most proximal points of the ulnar and radial metaphyses (PRPR) and the distance between the most distal points of both (DIDI). Intraclass correlation coefficients (ICCs) for intermethod consistency and inter- and intrarater agreement were calculated using a two-way ANOVA model. Variability and limits of agreement were determined using the Bland-Altman method. RESULTS: The interrater ICC was 0.75 (95% CI, 0.61-0.84) for the adapted perpendicular method, 0.88 (95% CI, 0.80-0.93) for PRPR, and 0.94 (95% CI, 0.90-0.97) for DIDI. The intermethod consistency ICC was 0.60 (95% CI, 0.48-0.70) for perpendicular versus PRPR and 0.60 (95% CI, 0.49-0.70) for perpendicular versus DIDI. The intrarater ICC was 0.88 (95% CI, 0.70-0.95) for perpendicular, 0.90 (95% CI, 0.83-0.94) for PRPR, and 0.81 (95% CI, 0.69-0.89) for DIDI. The perpendicular method was not useable in 38 cases (skeletal age ≤ 9 years) and the Hafner method in 79 cases (skeletal age ≥ 12 years). CONCLUSIONS: The perpendicular and Hafner methods show moderate intermethod consistency. The Hafner method is preferred for children with skeletal ages < 14 years, with good to excellent inter- and intrarater agreement. The adapted perpendicular method is recommended for patients with skeletal ages ≥ 14 years. KEY POINTS: • The perpendicular method for measuring ulnar variance requires extended instructions to ensure good interrater agreement in pediatric and adolescent patients. • The Hafner method is recommended for ulnar variance measurement in children with unfused growth plates and up to a skeletal age of 13 years, and the perpendicular method is recommended for children with fused growth plates and from skeletal age 14 and older. • The mean ulnar variance measured in this study for each skeletal age group (range, 5-18 years) is provided, to serve as a reference for future ulnar variance measurements using both methods in clinical practice.

Risk of chronic ankle instability: A reliability study on radiographic assessment of the ankle joint geometry.

BACKGROUND: Chronic ankle instability (CAI) is a multifactorial disabling condition. Ideally all factors contributing to CAI are identified and implemented in a risk assessment model. However, they need to meet strict reliability requirements. To assess usability of radiographic factors for this risk assessment model and future clinical practice, the objective of the current study was to assess the intra and inter observer reliability of three radiographic measurements. METHODS AND METHODS: The radiographs of 39 consecutive patients, at least 16years, who visited the Emergency Department after sustaining a lateral ankle sprain (LAS), were assessed by four observers. The radiographic measurements included absolute and relative ankle alignment, sagittal fibular position and ankle joint congruency (talar radius and height, and tibiotalar sector), performed twice by all observers independently. Reliability was assessed by calculating the Intraclass Correlation Coefficient (ICC) which was considered good when ICC>0.70. RESULTS: The intra observer reliability of the absolute and relative fibular position, and talar height were good to excellent, (ICC 0.84-0.98, 0.85-0.98, and 0.79-0.93, respectively). The talar radius (ICC 0.69-0.89) was moderate to good. The overall inter observer reliability was good for the absolute and relative fibular position, and talar radius (ICC 0.84, 0.86, and 0.79, respectively). Other measurements had ICC values of <0.70. CONCLUSIONS: In an effort to identify the multifactorial nature of CAI, both the fibular position and the talar radius measurements showed good observer reliability, and will be implemented in a future risk assessment models. The other measurements are too prone for measurement errors, for future reference. LEVEL OF EVIDENCE: IV Case Series.

A risk assessment model for chronic ankle instability: indications for early surgical treatment? An observational prospective cohort - study protocol.

BACKGROUND: Chronic ankle instability (CAI) is a common result of an ankle sprain. Even though early surgical treatment yields the best results, overall only professional athletes are eligible for acute surgical stabilization. Treating all patients with early surgical stabilization leads to a high amount of unnecessary invasive interventions, as not all patients progress to CAI. If patients at risk of developing CAI can be identified, treatment policies may be applied more effectively and efficiently. The purpose of this study is to develop a risk assessment model to identify patients at risk for CAI that should receive early surgical treatment. METHODS: In this observational prospective cohort, all patients aged sixteen years and older, reporting at the emergency department of one of the participating hospitals after sustaining a lateral ankle sprain, and filled out 1 out of 3 follow-up questionnaires and the 1 year follow-up are included. A lateral and anteroposterior radiograph is made. Patients are excluded if a fracture or other pathology is present. The included patients receive four questionnaires, including questions focusing on the sprain, treatment and complaints, the Foot and Ankle Outcome Score and the Cumberland Ankle Instability Tool. A total of eleven radiographic variables are assessed for inter- and intra-observer reliability. Additionally, four factors extracted from the questionnaires, will be evaluated for correlation with CAI. Significantly correlating factors (e.a. risk factors) will be implemented in a risk assessment model. For the final model, based on sixteen variables with a minimum of 20 events per variable and a prevalence of 30-40% after an initial sprain, a sample size of 2370 patients is needed to perform both internal and external model validation. DISCUSSION: This study will develop the first large scale model for the risk at CAI after an ankle sprain combining radiographic and patient characteristics. With this risk assessment model, patients at risk for CAI may be identified and properly informed on the treatment options. Patients identified as being at risk, may receive more adequate follow-up and become eligible for early surgical stabilization. This prevents patients from experiencing unnecessary long-lasting complaints, increasing the success rate of conservative and surgical treatment. TRIAL REGISTRATION: Retrospectively registered: NCT02955485 [Registration date: 3-11-2016]. NTR6139 [Registration date: 3-1-2017].

Systematic assessment of the growth plates of the wrist in young gymnasts: development and validation of the Amsterdam MRI assessment of the Physis (AMPHYS) protocol.

OBJECTIVES: To develop and validate a protocol for MRI assessment of the distal radial and ulnar periphyseal area in gymnasts and non-gymnasts. METHODS: Twenty-four gymnasts with wrist pain, 18 asymptomatic gymnasts and 24 non-gymnastic controls (33 girls) underwent MRI of the wrist on a 3T scanner. Sequences included coronal proton density-weighted images with and without fat saturation, and three-dimensional water-selective cartilage scan and T2 Dixon series. Skeletal age was determined using hand radiographs. Three experienced musculoskeletal radiologists established a checklist of possible (peri)physeal abnormalities based on literature and clinical experience. Five other musculoskeletal radiologists and residents evaluated 30 MRI scans (10 from each group) using this checklist and reliability was determined using the intraclass correlation coefficient (ICC) and Fleiss' kappa. A final evaluation protocol was established containing only items with fair to excellent reliability. RESULTS: Twenty-seven items were assessed for reliability. Intra-rater and inter-rater agreement was good to excellent (respective ICCs 0.60-0.91 and 0.60-0.78) for four epiphyseal bone marrow oedema-related items, physeal signal intensity, metaphyseal junction and depth of metaphyseal intrusions. For physeal thickness, thickness compared with proximal physis of first metacarpal, metaphyseal intrusions, physeal connection of intrusions and metaphyseal bone marrow signal intensity, intra-rater agreement was fair to excellent (ICC/kappa 0.55-0.85) and inter-rater agreement was fair (ICC/kappa 0.41-0.59). Twelve items were included in the final protocol. CONCLUSION: The Amsterdam MRI assessment of the Physis protocol facilitates patient-friendly and reliable assessment of the (peri)physeal area in the radius and ulna.

Lowering iodinated contrast concentration in infrainguinal endovascular interventions: a three-armed randomized controlled non-inferiority trial.

OBJECTIVES: To determine the influence of lowering iodinated contrast concentration on confidence of interventional radiologists in diagnosing and treating lesions during endovascular interventions in patients with symptomatic peripheral arterial disease (PAD). METHODS: A randomized controlled non-inferiority trial was performed in 60 patients. Intervention was performed with contrast concentrations (in mg of iodine per mL, mgI/mL) of 300 (standard), 240, or 140 mgI/mL. Primary outcome was confidence (score 0-100 %) of radiologists in diagnosing and treating arterial lesions. Secondary outcomes were procedural iodine load and image quality (i.e. non-diagnostic, limited, diagnostic, exemplary). RESULTS: Median confidence scores in diagnosing lesions were 100 % (range 81-100 %) for the 300 group (n = 21), 100 % (range 82-100 %) for the 240 group (n = 19), and 100 % (range 91-100 %) for the 140 group (n = 20) (both p = 1.00 compared to the 300 group). Median scores for treating lesions in the 240 and 140 groups, 100 % (range 79-100 %, p = 0.40), and 100 % (range 63-100 %, p = 0.25), respectively, were not lower compared to the 300 group (median 100 %, range 78-100 %). Procedural iodine load was lower in the 240 (24.3 ± 7.6 g, p = 0.022) and 140 groups (17.8 ± 5.6 g, p < 0.001) compared to the 300 group (29.7 ± 6.3 g). Image quality was diagnostic for all groups. CONCLUSION: Using iodine contrast of 140 mgI/mL for diagnosis and interventions in PAD patients significantly reduces administered iodine load without compromising image quality. Future use of lower iodine dose is recommended. KEY POINTS: • Lower iodinated contrast concentration during endovascular intervention does not decrease radiologist's confidence. • Image quality of standardized angiographies remains diagnostic using 140 mgI/mL iodinated contrast concentration. • Iodine load during intervention can be decreased by >40 % when using 140 mgI/mL. • Implementing the use of a lower iodinated contrast concentration will reduce the costs of the procedure.

CT angiography and magnetic resonance angiography findings after surgical and interventional radiology treatment of peripheral arterial obstructive disease.

In the last years, technical innovations in the field of CT angiography (CTA) and magnetic resonance angiography (MRA) have allowed accurate and highly detailed evaluation of peripheral vascular pathologies. This has dramatically changed the diagnostic approach in treatment planning of peripheral arterial obstructive disease and also enabling early identification of treatment failure or treatment-related complications after surgical or endovascular procedures. Although Doppler Ultrasound is the first-line imaging modality during follow-up after treatment, its role is currently diminishing in importance mostly because of the proliferation of high-end CT and MR scanners capable of fast, reproducible, and highly reliable vascular imaging. The aim of this study is to review the various surgical and endovascular procedures for peripheral arterial obstructive disease and to provide CTA and MRA samples of common and uncommon complications related to treatment.

Outcomes of infrainguinal revascularizations with endovascular first strategy in critical limb ischemia.

PURPOSE: This study was designed to study the outcome of infrainguinal revascularization in patients with critical limb ischemia (CLI) in an institution with a preference towards endovascular intervention first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age. METHODS: A prospective, observational cohort study was conducted between May 2007 and May 2010 in patients presenting with CLI. At baseline, the optimal treatment was selected, i.e., endovascular or surgical treatment. In case of uncertainty about the preferred treatment, a multidisciplinary team (MDT) was consulted. Primary endpoints were quality of life and functional status 6 and 12 months after initial intervention, assessed by the VascuQol and AMC Linear Disability Score questionnaires, respectively. RESULTS: In total, 113 patients were included; 86 had an endovascular intervention and 27 had surgery. During follow-up, 41 % underwent an additional ipsilateral revascularisation procedure. For the total population, and endovascular and surgery subgroups, the VascuQol sum scores improved after 6 and 12 months (p < 0.01 for all outcomes) compared with baseline. The functional status improved (p = 0.043) after 12 months compared with baseline for the total population. Functional status of the surgery subgroup improved significantly after 6 (p = 0.031) and 12 (p = 0.044) months, but not that of the endovascular subgroup. CONCLUSIONS: Overall, the strategy of performing endovascular treatment first in patients with poor condition, unfavourable anatomy for surgery, no venous material for bypass, and old age has comparable or even slightly better results compared with the BASIL trial and other cohort studies. All vascular groups should discuss whether their treatment strategy should be directed at treating CLI patients preferably endovascular first and consider implementing an MDT to optimize patient outcomes.

Perfusion angiography of the foot in patients with critical limb ischemia: description of the technique.

OBJECTIVE: To study the feasibility of 2D perfusion imaging in critical limb ischemia (CLI). METHODS/RESULTS: Perfusion angiography is a new technology which was tested in 18 patients with CLI of the foot. A standardized protocol was used with a catheter placed at the mid-part of the popliteal artery, and a total of 9 cc of non-ionic iodinated contrast material was injected at a rate of 3 cc/sec. The technology is based on early cardiology research where iodinated contrast agents were used for imaging of cardiac perfusion. During the first pass of the contrast, there is a significant diffusion of the contrast agents into the interstitial space, particularly for non-ionic and low-molecular-weight compounds. DISCUSSION: The original angiography data can be used to make a time-density curve, which represents the actual perfusion of the foot in time. Angiographic perfusion imaging is a post-processing modality for which no extra contrast or radiation is needed. With this technique, it is possible to get more information about the perfusion status and microcirculation of the foot. This is a step toward functional imaging in CLI patients.

Antioxidants for pain in chronic pancreatitis.

BACKGROUND: Reduced intake and absorption of antioxidants due to pain and malabsorption are probable causes of the lower levels of antioxidants observed in patients with chronic pancreatitis (CP). Improving the status of antioxidants might be effective in slowing the disease process and reducing pain in CP. OBJECTIVES: To assess the benefits and harms of antioxidants for the treatment of pain in patients with CP. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Conference Proceedings Citation Index from inception to October 2012. Two review authors performed the selection of trials independently. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) evaluating antioxidants for treatment of pain in CP. All trials were included irrespective of blinding, numbers of participants randomly assigned and language of the article. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. The risk of bias of included trials was assessed. Study authors were asked for additional information in the case of missing data. MAIN RESULTS: Twelve RCTs with a total of 585 participants were included. Six trials were double-blinded, placebo-controlled studies, and the other six trials were of less adequate methodology. Most trials were small and had high rates of dropout. Eleven of the 12 included trials described the effects of antioxidants on chronic abdominal pain in chronic pancreatitis. Pain as measured on a visual analogue scale (VAS, scale range 0 to 10) after one to six months was less in the antioxidant group than in the control group (mean difference (MD) -0.33, 95% confidence interval (CI) -0.64 to -0.02, P value 0.04, moderate-quality evidence). The number of pain-free participants was not statistically significantly different (risk ratio (RR) 1.73, 95% CI 0.95 to 3.15, P value 0.07, low-quality evidence). More adverse events were observed in the antioxidant group, both in the parallel trials (RR 4.43, 95% CI 1.60 to 12.29, P value 0.0004, moderate-quality evidence) and in the cross-over trials (RR 5.80, 95% CI 1.56 to 21.53, P value 0.0009, moderate-quality evidence). Adverse events occurred in 16% of participants and were mostly mild (e.g. headache, gastrointestinal complaints), but were sufficient to make participants stop antioxidant use. Other important outcomes such as use of analgesics, exacerbation of pancreatitis and quality of life were rarely reported. One trial from 1991 evaluated the effects of antioxidants on acute pain during exacerbation of chronic pancreatitis and found that a significantly higher proportion of participants in the antioxidant group experienced pain relief. This trial was conducted more than 25 years ago and has not been reproduced since that time. Therefore, additional trials are needed before reliable conclusions can be drawn. AUTHORS' CONCLUSIONS: Current evidence shows that antioxidants can reduce pain slightly in patients with chronic pancreatitis. The clinical relevance of this small reduction is uncertain, and more evidence is needed. Adverse events in one of six patients may prevent the use of antioxidants. Effects of antioxidants on other outcome measures, such as use of analgesics, exacerbation of pancreatitis and quality of life remain uncertain because reliable data are not available.

Diagnostic performance of computed tomography angiography and contrast-enhanced magnetic resonance angiography in patients with critical limb ischaemia and intermittent claudication: systematic review and meta-analysis.

OBJECTIVE: To evaluate the diagnostic performance of computed tomography angiography (CTA) and contrast-enhanced magnetic resonance angiography (CE-MRA) in detecting haemodynamically significant arterial stenosis or occlusion in patients with critical limb ischaemia (CLI) or intermittent claudication (IC). METHODS: Medline and Embase were searched for studies comparing CTA or CE-MRA with digital subtraction angiography as a reference standard, including patients with CLI or IC. Outcome measures were aortotibial arterial stenosis of more than 50 % or occlusion. Methodological quality of studies was assessed using QUADAS. RESULTS: Out of 5,693 articles, 12 CTA and 30 CE-MRA studies were included, respectively evaluating 673 and 1,404 participants. Summary estimates of sensitivity and specificity were respectively 96 % (95 % CI, 93-98 %) and 95 % (95 % CI, 92-97 %) for CTA, and 93 % (95 % CI, 91-95 %) and 94 % (95 % CI, 93-96 %) for CE-MRA. Regression analysis showed that the prevalence of CLI in individual studies was not an independent predictor of sensitivity and specificity for either technique. Methodological quality of studies was moderate to good. CONCLUSION: CTA and CE-MRA are accurate techniques for evaluating disease severity of aortotibial arteries in patients with CLI or IC. No significant differences in the diagnostic performance of the two techniques between patients with CLI and IC were found. KEY POINTS: • Computed tomography and contrast-enhanced magnetic resonance angiography can both demonstrate arterial disease. • CTA and CE-MRA can both accurately evaluate arteries in peripheral arterial disease. • Diagnostic performances of critical limb ischaemia and intermittent claudication are not different. • Separate imaging technique of tibial arteries by CE-MRA is preferred. • CTA and CE-MRA can distinguish confidently between high-grade stenoses and occlusions.

The relationship of walking distances estimated by the patient, on the corridor and on a treadmill, and the Walking Impairment Questionnaire in intermittent claudication.

OBJECTIVE: Physicians and patients consider the limited walking distance and perceived disability when they make decisions regarding (invasive) treatment of intermittent claudication (IC). We investigated the relationship between walking distances estimated by the patient, on the corridor and on a treadmill, and the Walking Impairment Questionnaire (WIQ) in patients with IC due to peripheral arterial disease. METHODS: This was a single-center, prospective observational cohort study at a vascular laboratory in a university hospital in the Netherlands. The study consisted of 60 patients (41 male) with a median age of 64 years (range, 44-86 years) with IC and a walking distance ≤ 250 m on a standardized treadmill test. Main outcome measures were differences and Spearman rank correlations between pain-free walking distance, maximum walking distance (MWD) estimated by the patient, on the corridor and on a standardized treadmill test, and their correlation with the WIQ. RESULTS: The median patients' estimated, corridor, and treadmill MWD were 200, 200, and 123, respectively (P < .05). Although the median patients' estimated and corridor MWD were not significantly different, there was a difference on an individual basis. The correlation between the patients' estimated and corridor MWD was moderate (r = 0.61; 95% confidence interval [CI], 0.42-0.75). The correlation between patients' estimated and treadmill MWD was weak (r = 0.39; 95%, CI 0.15-0.58). Respective correlations for the pain-free walking distance were comparable. The patients' estimated MWD was moderately correlated with WIQ total score (r = 0.63; 95%, CI 0.45-0.76) and strongly correlated with WIQ distance score (r = 0.81; 95% CI, 0.69-0.88). The correlation between the corridor MWD and WIQ distance score was moderate (r = 0.59; 95% CI, 0.40-0.74). CONCLUSIONS: Patients' estimated walking distances and on a treadmill do not reflect walking distances in daily life. Instruments that take into account the perceived walking impairment, such as the WIQ, may help to better guide and evaluate treatment decisions.

Three-dimensional rotational angiography of the foot in critical limb ischemia: a new dimension in revascularization strategy.

PURPOSE: To evaluate the additional value of three-dimensional rotational angiography (3DRA) of the foot compared with digital subtraction angiography (DSA) in patients with critical limb ischemia (CLI). TECHNIQUE: For 3DRA, the C-arm was placed in the propeller position with the foot in an isocentric position. The patient's unaffected foot was positioned in a footrest outside the field of view. For correct timing of 3DRA, the delay from contrast injection in the popliteal artery at the level of knee joint to complete pedal arterial enhancement was assessed using DSA. With this delay, 3DRA was started after injection of 15 ml contrast. Imaging of the 3DRA could directly be reconstructed and visualized. MATERIALS AND METHODS: Patients undergoing 3DRA of the foot were prospectively registered. DSA and 3DRA images were scored separately for arterial patency and presence of collaterals. Treatment strategies were proposed based on DSA with and without the availability of 3DRA. RESULTS: Eleven patients underwent 3DRA of the foot. One 3DRA was not included because the acquisition was focused on the heel instead of the entire foot. Diagnostic quality of 3DRA was good in all ten patients. 3DRA compared with DSA showed additional patent arteries in six patients, patent plantar arch in three patients, and collaterals between the pedal arteries in five patients. Additional information from 3DRA resulted in a change of treatment strategy in six patients. CONCLUSION: 3DRA of the foot contains valuable additional real-time information to better guide peripheral vascular interventions in patients with CLI and nonhealing tissue lesions.

Clinical outcome in relation to timing of surgery in chronic pancreatitis: a nomogram to predict pain relief.

OBJECTIVE: To evaluate the effect of timing of surgery on the long-term clinical outcome of surgery in chronic pancreatitis (CP). DESIGN: Cohort study with long-term follow-up. SETTING: Five specialized academic centers. PATIENTS: Patients with CP treated surgically for pain. INTERVENTIONS: Pancreatic resection and drainage procedures for pain relief. MAIN OUTCOME MEASURES: Pain relief (pain visual analogue score ≤4), pancreatic function, and quality of life. RESULTS: We included 266 patients with median follow-up of 62 months (interquartile range, 31-112). Results were presented as odds ratios (ORs)with 95% confidence intervals after correction for bias using bootstrap-corrected analysis. Pain relief was achieved in 149 patients (58%). Surgery within 3 years of symptoms was independently associated with more pain relief (OR, 1.8; 95% CI, 1.0-3.4; P = .03) and less endocrine pancreatic insufficiency (OR, 0.57; 95% CI, 0.33-0.96; P = .04). More pain relief was also observed in patients not taking opioids preoperatively (OR, 2.1; 95% CI, 1.2-4.0; P = .006) and who had 5 or fewer endoscopic treatments prior to surgery (OR, 2.5; 95% CI, 1.1-6.3; P = .04). The probability of achieving pain relief varied between 23% and 75%, depending on these risk factors. CONCLUSIONS: The timing of surgery is an important risk factor for clinical outcome in CP. Surgery may need to be considered at an earlier phase than it is now, preferably within 3 years of symptomatic CP. Likelihood of postoperative pain relief can be calculated on an individual basis using the presented nomogram.