VMC++ versus BEAMnrc: a comparison of simulated linear accelerator heads for photon beams

BEAMnrc, a code for simulating medical linear accelerators based on EGSnrc, has been bench-marked and used extensively in the scientific literature and is therefore often considered to be the gold standard for Monte Carlo simulations for radiotherapy applications. However, its long computation times make it too slow for the clinical routine and often even for research purposes without a large investment in computing resources. VMC++ is a much faster code thanks to the intensive use of variance reduction techniques and a much faster implementation of the condensed history technique for charged particle transport. A research version of this code is also capable of simulating the full head of linear accelerators operated in photon mode (excluding multileaf collimators, hard and dynamic wedges). In this work, a validation of the full head simulation at 6 and 18 MV is performed, simulating with VMC++ and BEAMnrc the addition of one head component at a time and comparing the resulting phase space files. For the comparison, photon and electron fluence, photon energy fluence, mean energy, and photon spectra are considered. The largest absolute differences are found in the energy fluences. For all the simulations of the different head components, a very good agreement (differences in energy fluences between VMC++ and BEAMnrc <1%) is obtained. Only a particular case at 6 MV shows a somewhat larger energy fluence difference of 1.4%. Dosimetrically, these phase space differences imply an agreement between both codes at the <1% level, making VMC++ head module suitable for full head simulations with considerable gain in efficiency and without loss of accuracy.

Forget the blood, not the stone! Microhaematuria in acute urolithiasis and the role of early CT scanning

BACKGROUND: Although urinalysis is simple and inexpensive to perform, the finding of microhaematuria on urinalysis may be unreliable for diagnosing urolithiasis. OBJECTIVE: To evaluate microhaematuria as a diagnostic marker for urolithiasis compared with low-dose unenhanced multidetector computed tomography (MDCT) as the "gold standard". SETTING: A level 1 emergency department in a tertiary referral university teaching hospital. DESIGN: Retrospective analysis. METHODS: A study was undertaken to assess whether the finding of microhaematuria was diagnostic for urolithiasis using a low-dose unenhanced MDCT-based diagnosis as the reference standard by reviewing the records of all patients who presented to the emergency department with colicky flank pain and underwent a CT scan between January 2003 and December 2005. RESULTS: Urolithiasis was present (as defined by low-dose unenhanced MDCT) in 507/638 patients (79%); 341/638 (53%) were true positive for urolithiasis, 76 (12%) were true negative, 55 (9%) were false positive and 166 (26%) were false negative. Microhaematuria as a test for urolithiasis in patients presenting to the emergency department therefore has a sensitivity, specificity, positive predictive value and negative predictive value of 67%, 58%, 86% and 31%, respectively. 58% of the urinalysis results were negative for haematuria in the subset of patients with significant alternative diagnoses. CONCLUSIONS: The sensitivity, specificity and negative predictive value of microhaematuria on urinalysis for urolithiasis using unenhanced MDCT as the reference standard were low. This suggests that, when urolithiasis is clinically suspected, unenhanced MDCT is indicated without urinalysis being a prerequisite.

Pelvic radiography in ATLS algorithms: A diminishing role?

ABSTRACT: BACKGROUND: Pelvic x-ray is a routine part of the primary survey of polytraumatized patients according to Advanced Trauma Life Support (ATLS) guidelines. However, pelvic CT is the gold standard imaging technique in the diagnosis of pelvic fractures. This study was conducted to confirm the safety of a modified ATLS algorithm omitting pelvic x-ray in hemodynamically stable polytraumatized patients with clinically stable pelvis in favour of later pelvic examination by CT scan. METHODS: We conducted a retrospective analysis of all polytraumatized patients in our emergency room between 01.07.2004 and 31.01.2006. Inclusion criteria were blunt abdominal trauma, initial hemodynamic stability and a stable pelvis on clinical examination. We excluded patients requiring immediate intervention because of hemodynamic instability. RESULTS: We reviewed the records of n = 452 polytraumatized patients, of which n = 91 fulfilled inclusion criteria (56% male, mean age = 45 years). The mechanism of trauma included 43% road traffic accidents, 47% falls. In 68/91 (75%) patients, both a pelvic x-ray and a CT examination were performed; the remainder had only pelvic CT. In 6/68 (9%) patients, pelvic fracture was diagnosed by pelvic x-ray. None of these 6 patients was found having a false positive pelvic x-ray, i.e. there was no fracture on pelvic CT scan. In 3/68 (4%) cases a fracture was missed in the pelvic x-ray, but confirmed on CT (false negative on x-ray). None of the diagnosed fractures needed an immediate therapeutic intervention. 5 (56%) were classified type A fractures, and another 4 (44%) B 2.1 in computed tomography (AO classification). One A 2.1 fracture was found in a clinically stable patient who only received CT scan (1/23). CONCLUSION: While pelvic x-ray is an integral part of ATLS assessment, this retrospective study suggests that in hemodynamically stable patients with clinically stable pevis, its sensitivity is only 67% and it may safely be omitted in favor of a pelvic CT examination if such is planned in adjunct assessment and available. The results support the safety and utility of our modified ATLS algorithm. A randomized controlled trial using the algorithm can safely be conducted to confirm the results.

Radiographic analysis of femoroacetabular impingement with Hip2Norm-reliable and validated

The purpose of this study was to validate the accuracy, consistency, and reproducibility/reliability of a new method for correction of pelvic tilt and rotation of radiographic hip parameters for pincer type of femoroacetabular impingement on an anteroposterior pelvic radiograph. Thirty cadaver hips and 100 randomized, blinded AP pelvic radiographs were used for investigation. To detect the software accuracy, the calculated femoral head coverage and classic hip parameters determined with our software were compared to reference measurements based on CT scans or conventional radiographs in a neutral orientation as gold standard. To investigate software consistency, differences among the different parameters for each cadaver pelvis were calculated when reckoned back from a random to the neutral orientation. Intra- and interobserver comparisons were used to analyze the reliability and reproducibility of all parameters. All but two parameters showed a good-to-very good accuracy with the reference measurements. No relevant systematic errors were detected in the Bland-Altman analysis. Software consistency was good-to-very good for all parameters. A good-to-very good reliability and reproducibility was found for a substantial number of the evaluated radiographic acetabular parameters. The software appears to be an accurate, consistent, reliable, and reproducible method for analysis of acetabular pathomorphologies.

Reprint of "Stereology meets electron tomography: towards quantitative 3D electron microscopy" [J. Struct. Biol. 159 (2007) 443-450]

Stereological tools are the gold standard for accurate (i.e., unbiased) and precise quantification of any microscopic sample. The past decades have provided a broad spectrum of tools to estimate a variety of parameters such as volumes, surfaces, lengths, and numbers. Some of them require pairs of parallel sections that can be produced by either physical or optical sectioning, with optical sectioning being much more efficient when applicable. Unfortunately, transmission electron microscopy could not fully profit from these riches, mainly because of the large depth of field. Hence, optical sectioning was a long-time desire for electron microscopists. This desire was fulfilled with the development of electron tomography that yield stacks of slices from electron microscopic sections. Now, parallel optical slices of a previously unimagined small thickness (2-5nm axial resolution) can be produced. These optical slices minimize problems related to overprojection effects, and allow for direct stereological analysis, e.g., volume estimation with the Cavalieri principle and number estimation with the optical disector method. Here, we demonstrate that the symbiosis of stereology and electron tomography is an easy and efficient way for quantitative analysis at the electron microscopic level. We call this approach quantitative 3D electron microscopy.

A semi-structured interview to assess visual hallucinations in older people

OBJECTIVE: Visual hallucinations are under-reported by patients and are often undiscovered by health professionals. There is no gold standard available to assess hallucinations. Our objective was to develop a reliable, valid, semi-structured interview for identifying and assessing visual hallucinations in older people with eye disease and cognitive impairment. METHODS: We piloted the North-East Visual Hallucinations Interview (NEVHI) in 80 older people with visual and/or cognitive impairment (patient group) and 34 older people without known risks of hallucinations (control group). The informants of 11 patients were interviewed separately. We established face validity, content validity, criterion validity, inter-rater agreement and the internal consistency of the NEVHI, and assessed the factor structure for questions evaluating emotions, cognitions, and behaviours associated with hallucinations. RESULTS: Recurrent visual hallucinations were common in the patient group (68.8%) and absent in controls (0%). The criterion, face and content validities were good and the internal consistency of screening questions for hallucinations was high (Cronbach alpha: 0.71). The inter-rater agreements for simple and complex hallucinations were good (Kappa 0.72 and 0.83, respectively). Four factors associated with experiencing hallucinations (perceived control, pleasantness, distress and awareness) were identified and explained a total variance of 73%. Informants gave more 'don't know answers' than patients throughout the interview (p = 0.008), especially to questions evaluating cognitions and emotions associated with hallucinations (p = 0.02). CONCLUSIONS: NEVHI is a comprehensive assessment tool, helpful to identify the presence of visual hallucinations and to quantify cognitions, emotions and behaviours associated with hallucinations.

[Diagnosis, treatment and follow up of prostata cancer]

Prostate cancer is the most frequent diagnosed malignancy in men with an increasing incidence. In well informed men between the age of 50 and 70 years screening should be offered when requested. Not every newly diagnosed prostate cancer requires immediate treatment. Curative treatment should be offered to men with a minimal life expectancy of 10 years. In men older than 50-75 years, therefore further screening is not necessary due to a lack of a therapeutic consequence. Curative treatment options enclose as the gold standard surgical removal, i.e. open radical prostatectomy with pelvic lymph node dissection, and radio-oncologic treatments, be it percutaneous radiation therapy, brachytherapies or a combination thereof. Palliative treatment options are mainly hormonal treatment (medical or surgical androgen deprivation), local radiation, treatment with bisphosphonates, chemotherapy and surgical desobstruction of the prostate. Regular follow up allows for early detection of recurrences and an active treatment concept.

[Treatment of lymphangiomas with picibanil in the first year of life]

BACKGROUND: The therapeutic gold standard of cystic hygroma is its complete resection. Because of its growth pattern and its main location in the head and neck region complete resection is not always possible. An alternative is the local injection of Picibanil, but only few cases have been published about its use in infants. PATIENTS/METHOD: We retrospectively analyzed the data of 8 infants (age: 2 weeks-12 months) who got Picibanil therapy because of cystic hygroma in the time period 2002 until 2006. Follow up ranged from 3 months up to 3 years. RESULTS: During the postoperative period all patients had local swelling, in 4 cases accompanied with local inflammation and fever. Tumor reduction of >50% was obtained in 7 of 8 patients. CONCLUSIONS: Local injection of Picibanil in infants with cystic hygroma seems to be a safe alternative to surgical therapy, especially when complete tumor resection means damage of important neighbouring structures. Prospective trials are necessary to confirm the better outcome after therapy with Picibanil compare to primary surgery.

Strategies for routine biopsies in heart transplantation based on 8-year results with more than 13,000 biopsies

The endomyocardial biopsy (EMB) in heart transplant recipients has been considered the "gold standard" for diagnosis of graft rejection (REJ). The purpose of this retrospective study is to develop long-term strategies (frequency and postoperative duration of EMB) for REJ monitoring. Between 1985 and 1992, 346 patients (mean age 44.5 years, female patients = 14%) received 382 heart grafts. For graft surveillance EMBs were performed according to a fixed schedule depending on postoperative day and the results of previous biopsies. In the first year the average number (no.) of EMBs/patient was 20 with 19% positive for REJ in the first quarter, dropping to 7% REJ/EMB by the end of the first year. The percentage of REJ/EMB declined annually from 4.7% to 4.5%, 2.2% and less than 1% after the fifth year. Individual biopsy results in the first 3 postoperative months had little predictive value. Patients with fewer than two REJ (group 1), vs patients with two or more REJ in the first 6 postoperative months (group 2), were significantly less likely to reject in the second half of the first year (group 1: 0.29 +/- 0.6 REJ/patient; group 2:0.83 +/- 1.3 REJ/patient; P < 0.001) and third postoperative year (group 1:0.12 +/- 0.33 REJ/patients; group 2:0.46 +/- 0.93 REJ/patient; P < 0.05). In conclusion, routine EMBs in the first 3 postoperative months have only limited predictive value, however the number of routine EMBs can be drastically reduced later depending on the intermediate postoperative REJ pattern.

Could full-body digital X-ray (LODOX-Statscan) screening in trauma challenge conventional radiography?

ATLS Guidelines recommend single plain radiography of the chest and pelvis as part of the primary survey. Such isolated radiographs, usually obtained by bedside machines, can result in limited, low-quality studies that can adversely affect management. A new digital, low-radiation imaging device, the "Lodox Statscan" (LS), provides full-body anterior and lateral views based on enhanced linear slot-scanning technology in just over 5 minutes. We have the first LS in Europe at our facility. The aim of this study was to compare LS with computed tomographic (CT) scanning, as the gold standard, to determine the sensitivity of LS investigation in detecting injuries to the chest, thoracolumbar spine, and pelvis from our own experience, and to compare our findings with those of conventional radiography in the literature.

Noninvasive measurement of cardiac output during exercise by inert gas rebreathing technique

Reduced exercise tolerance and dyspnea during exercise are hallmarks of heart failure syndrome. Exercise capacity and various parameters of cardiopulmonary response to exercise are of important prognostic value. All the available parameters only indirectly reflect left ventricular dysfunction and hemodynamic adaptation to an increased demand. Noninvasive assessment of cardiac output, especially during an incremental exercise stress test, would allow the direct measure of cardiac reserve and may become the gold standard for prognostic evaluation in the future.

Comparison of multiplex ligation-dependent probe amplification and real-time PCR accuracy for gene copy number quantification using the beta-defensin locus

The reliable quantification of gene copy number variations is a precondition for future investigations regarding their functional relevance. To date, there is no generally accepted gold standard method for copy number quantification, and methods in current use have given inconsistent results in selected cohorts. In this study, we compare two methods for copy number quantification. beta-defensin gene copy numbers were determined in parallel in 80 genomic DNA samples by real-time PCR and multiplex ligation-dependent probe amplification (MLPA). The pyrosequencing-based paralog ratio test (PPRT) was used as a standard of comparison in 79 out of 80 samples. Realtime PCR and MPLA results confirmed concordant DEFB4, DEFB103A, and DEFB104A copy numbers within samples. These two methods showed identical results in 32 out of 80 samples; 29 of these 32 samples comprised four or fewer copies. The coefficient of variation of MLPA is lower compared with PCR. In addition, the consistency between MLPA and PPRT is higher than either PCR/MLPA or PCR/PPRT consistency. In summary, these results suggest that MLPA is superior to real-time PCR in beta-defensin copy number quantification.

Oscillometric measurement of ankle-brachial index in patients with suspected peripheral disease: comparison with Doppler method

QUESTION UNDER STUDY: Purpose was to validate accuracy and reliability of automated oscillometric ankle-brachial (ABI) measurement prospectively against the current gold standard of Doppler-assisted ABI determination. METHODS: Oscillometric ABI was measured in 50 consecutive patients with peripheral arterial disease (n = 100 limbs, mean age 65 +/- 6 years, 31 men, 19 diabetics) after both high and low ABI had been determined conventionally by Doppler under standardised conditions. Correlation was assessed by linear regression and Pearson product moment correlation. Degree of inter-modality agreement was quantified by use of Bland and Altman method. RESULTS: Oscillometry was performed significantly faster than Doppler-assisted ABI (3.9 +/- 1.3 vs 11.4 +/- 3.8 minutes, P <0.001). Mean readings were 0.62 +/- 0.25, 0.70 +/- 0.22 and 0.63 +/- 0.39 for low, high and oscillometric ABI, respectively. Correlation between oscillometry and Doppler ABI was good overall (r = 0.76 for both low and high ABI) and excellent in oligo-symptomatic, non-diabetic patients (r = 0.81; 0.07 +/- 0.23); it was, however, limited in diabetic patients and in patients with critical limb ischaemia. In general, oscillometric ABI readings were slightly higher (+0.06), but linear regression analysis showed that correlation was sustained over the whole range of measurements. CONCLUSIONS: Results of automated oscillometric ABI determination correlated well with Doppler-assisted measurements and could be obtained in shorter time. Agreement was particularly high in oligo-symptomatic non-diabetic patients.

Early diagnosis of temporomandibular joint involvement in juvenile idiopathic arthritis: a pilot study comparing clinical examination and ultrasound to magnetic resonance imaging

OBJECTIVES: To study the validity of both rheumatological and orthodontic examinations and ultrasound (US) as screening methods for early diagnosis of TMJ arthritis against the gold standard MRI. METHODS: Thirty consecutive juvenile idiopathic arthritis (JIA) patients were included in this pilot study. Rheumatological and orthodontic examinations as well as US were performed within 1 month of the MRI in a blinded fashion. Joint effusion and/or increased contrast enhancement of synovium or bone were considered signs of active arthritis on MRI. RESULTS: A total of 19/30 (63%) patients and 33/60 (55%) joints had signs of TMJ involvement on MRI. This was associated with condylar deformity in 9/19 (47%) patients and 15/33 (45%) joints. Rheumatological, orthodontic and US examinations correctly diagnosed 11 (58%), 9 (47%) and 6 (33%) patients, respectively, with active TMJ arthritis, but misdiagnosed 8 (42%), 10 (53%) and 12 (67%) patients, respectively, as having no signs of inflammation. The best predictor for active arthritis on MRI was a reduced maximum mouth opening. CONCLUSION: None of the methods tested was able to reliably predict the presence or absence of MRI-proven inflammation in the TMJ in our cohort of JIA patients. US was the least useful of all methods tested to exclude active TMJ arthritis.

Magic angle spinning magnetic resonance: a novel method opening up translational research into NAFLD?

NAFLD (non-alcoholic fatty liver disease) and NASH (non-alcoholic steatohepatitis) are of increasing importance, both in connection with insulin resistance and with the development of liver cirrhosis. Histological samples are still the 'gold standard' for diagnosis; however, because of the risks of a liver biopsy, non-invasive methods are needed. MAS (magic angle spinning) is a special type of NMR which allows characterization of intact excised tissue without need for additional extraction steps. Because clinical MRI (magnetic resonance imaging) and MRS (magnetic resonance spectroscopy) are based on the same physical principle as NMR, translational research is feasible from excised tissue to non-invasive examinations in humans. In the present issue of Clinical Science, Cobbold and co-workers report a study in three animal strains suffering from different degrees of NAFLD showing that MAS results are able to distinguish controls, fatty infiltration and steatohepatitis in cohorts. In vivo MRS methods in humans are not obtainable at the same spectral resolution; however, know-how from MAS studies may help to identify characteristic changes in crowded regions of the magnetic resonance spectrum.