EURADOS project on the impact of the proposed ICRU operational dose quantities.

Following the publication of the joint The International Commissions on Radiation Units and Measurements (ICRU) and on Radiological Protection (ICRP) report on new operational quantities for radiation protection, the European Dosimetry Group (EURADOS) have carried out an initial evaluation. The EURADOS report analyses the impact that the new quantities will have on: radiation protection practice; calibration and reference fields; European and national regulation; international standards and, especially, dosemeter and instrument design. The task group included experienced scientists drawn from across the various EURADOS working groups.

Conversion coefficients from total air kerma to the newly proposed ICRU/ICRP operational quantities for radiation protection for photon reference radiation qualities.

The International Commission on Radiation Units and Measurements (ICRU) has recently proposed a set of new operational quantities for radiation protection. ICRU supplied conversion coefficients for mono-energetic photons but not for photon reference radiation qualities defined by the International Organization for Standardization (ISO) in ISO 4037 and by the International Electrotechnical Commission (IEC) in IEC 61267. Therefore, in this work, conversion coefficients from total air kerma to the newly proposed operational quantities are averaged for photon reference radiation qualities. Also, parameters necessary to determine the influence of the air density on the conversion coefficients are determined. Finally, the impact of the newly proposed quantities upon the response of dosemeters is investigated.

Spectrometry of pulsed photon radiation.

The energy distribution (spectrum) of pulsed photon radiation can hardly be measured using active devices, therefore, a thermoluminescence detector (TLD)-based few-channel spectrometer is used in combination with a Bayesian data analysis to help resolve this problem. The spectrometer consists of 30 TLD layers interspaced by absorbers made of plastics and metals with increasing atomic numbers and thickness. Thus, the main idea behind the device is the deeper the radiation penetrates-the higher the radiation's energy when the radiation impinges perpendicular to the front of the spectrometer. From the doses measured in the TLD layers and from further prior available information, the photon spectrum is deduced using a Bayesian data analysis leading to absolute spectra and doses including their uncertainties and coverage intervals. This spectrometer was successfully used in two different scenarios, i.e. for the spectrometry of the radiation field two different industrial type open beam pulsed x-ray generators and secondly in three different radiation fields of a medical accelerator.

Conversion coefficients from absorbed dose to tissue to the newly proposed ICRU/ICRP operational quantities for radiation protection for beta reference radiation qualities.

The International Commission on Radiation Units and Measurements (ICRU) has, jointly with the International Commission on Radiological Protection (ICRP), recently proposed a set of new operational quantities for radiation protection in ICRU report 95. ICRU/ICRP supplied conversion coefficients for mono-energetic betas but not for beta reference radiation qualities defined by the International Organization for Standardization (ISO) in ISO 6980. Therefore, in this work, conversion coefficients from absorbed dose to tissue at a depth of 0.07 mm in a slab phantom to the newly proposed operational quantities are determined for beta reference radiation qualities. Finally, the impact of the newly proposed quantities on primary and calibration laboratories and on users and manufacturers of dosemeters is investigated, the latter by having a close look at the expected change of the response of dosemeters.

Endometrial Dating Method Detects Individual Maturation Sequences During the Secretory Phase.

BACKGROUND/AIM: This study assessed whether a new immunohistochemical dating method allows precise endometrial dating allowing optimal timing for embryo transfer. PATIENTS AND METHODS: A novel method was used for endometrial dating, with parameters including menstrual cycle days, Noyes histological criteria, along with immunohistochemical expression pattern of estrogen and progesterone receptors and proliferation marker Ki-67. Endometrial maturation was analyzed on days +5 to +10 after ovulation or progesterone administration in 217 biopsies from 151 subfertile patients during the secretory phase. RESULTS: Endometrial maturation varied individually, occurring 1.68±1.67 days late. Comparison of histological maturation with clinical days after ovulation showed a delay of about 2 days. CONCLUSION: Endometrial maturation requires 8 days, rather than the expected 6 days, to reach the histological mid-secretory phase. This is not a delay and is also seen in fertile patients. The new analysis method used is superior to that using Noyes criteria alone and provides a better basis for determining conditions for optimal timing of embryo transfers.

CONVERSION COEFFICIENTS FROM AIR KERMA TO DIRECTIONAL DOSE EQUIVALENT H'(0.07) FOR PHOTONS.

New conversion coefficients from air kerma free-in-air, Ka, to directional dose equivalent at 0.07mm depth, H'(0.07), are provided for monoenergetic values and for the spectra of the radiation qualities defined in ISO 4037-1. The interpolation procedure of the monoenergetic conversion coefficients from ICRU Report 57 was improved compared to former publications. The values resulting from the new interpolation procedure describe the energy dependence of the conversion coefficients more accurately and differ by up to 5% between 50keV and 100keV from former values. Due to an additional change of the extrapolation to low energies, the values for angles of radiation incidence above 60° and energies below 40keV changed by up to 50%. The influence on the spectrum weighted conversion coefficients is similar to the changes of the monoenergetic values.

Conversion coefficients for H'(3;Ω) for photons.

In this work, conversion coefficients for the operational quantity H'(3;Ω) have been calculated for both mono-energetic photons from 2 keV to 50 MeV for angles of incidence from 0° up to 180° in steps of 15° (to complement ICRU 57) as well as for photon reference radiation qualities (to complement ISO 4037). Finally, parameters necessary to determine the influence of the air density on the conversion coefficients have been determined.

Bowel preparation in pediatric colonoscopy: results of an open observational study.

BACKGROUND AND STUDY AIMS: The goal of this study was to analyze the bowel cleansing methods currently used for pediatric colonoscopy in terms of effectiveness, tolerance and safety. PATIENTS AND METHODS: Data from 768 colonoscopies reported by 28 centers were registered in an online database for further analysis. Binary logistic regression was used to determine how preparation methods affected the cleaning effect (Aronchick score) and the rate of adverse events (Aes) and complications. RESULTS: The most frequently reported cleansing agents were sodium picosulphate (54.2 %) and polyethylene-glycol (41.3 %) in various combinations. The cleaning effect was good to excellent in 72.6 % of patients. AEs during the preparation period occurred in 21.5 % of patients. Complications during endoscopy were reported in 12.1 % and were mostly mild. The different agents had no influence on the cleaning effect. In contrast the risk of AEs during preparation was significantly increased when polyethylene-glycol was used (odds ratio (OR) 2.112, P = 0.002) but reduced with the use of sodium picosulphate (OR 0.380, P < 0.001). In particular, the risk of needing a nasogastric tube to complete clean-out was about 10-fold higher when polyethylene-glycol was used. CONCLUSIONS: A large variety of regimens are used for bowel preparation in children. We found a good overall cleaning result independent of the agents used. Cleansing agents, on the other hand, had a significant influence on tolerance and safety.

Impact of radiation protection means on the dose to the lens of the eye while handling radionuclides in nuclear medicine.

The human eye lens appears to be more radiosensitive than previously assumed. The reduction of the limit for the dose to the lens of the eye to 20 mSv per year has been passed in the current Euratom Directives (2013). Therefore, in this work the impact of laboratory glasses and X-ray protective goggles was investigated and reciprocal attenuation factors (i.e. transmission factors) for different nuclides (Tc-99m, I-131, Y-90, F-18 and Ga-68) were determined. The radionuclides in typical geometry (syringe, applicator) were positioned at a distance of 50 cm to the eyes of four Alderson-Head-Phantoms. Different dosemeters measuring Hp(3) respective Hp(0.07) were fixed to the eyes of the phantoms, either behind the glasses or without any protection means, respectively. The mean reciprocal attenuation factors were determined to be between unity for F-18 and I-131 using laboratory glasses (no attenuation effect) and < 0.01 for Y-90 using X-ray protective goggles. All other results were between these extremes. It has been shown, that prospective doses to the lens of the eye can be reduced significantly by using appropriate radiation protection means, especially for those dose-relevant beta radiation emitting nuclides such as Y-90.

Dose rate constants for the quantity Hp(3) for frequently used radionuclides in nuclear medicine.

According to recent studies, the human eye lens is more sensitive to ionising radiation than previously assumed. Therefore, the dose limit for personnel occupationally exposed to ionising radiation will be lowered from currently 150 mSv to 20 mSv per year. Currently, no data base for a reliable estimation of the dose to the lens of the eye is available for nuclear medicine. Furthermore, the dose is usually not monitored. The aim of this work was to determine dose rate constants for the quantity Hp(3), which is supposed to estimate the dose to the lens of the eye. For this, Hp(3)-dosemeters were fixed to an Alderson Phantom at different positions. The dosemeters were exposed to radiation from nuclides typically used in nuclear medicine in their geometries analog to their application in nuclear medicine, e.g. syringe or vial. The results show that the handling of high-energy beta (i.e. electron or positron) emitters may lead to a relevant dose to the lens of the eye. For low-energy beta emitters and gamma emitters, an exceeding of the lowered dose limit seems to be unlikely.

Inflammatory bowel disease in pediatric patients: Characteristics of newly diagnosed patients from the CEDATA-GPGE Registry.

BACKGROUND: Inflammatory bowel disease (IBD) can arise at any age, with peak incidence in adolescence and young adulthood. A registry of pediatric cases of IBD offers the opportunity to document their diagnosis and treatment, with the ultimate aim of improving diagnosis and treatment in the future. METHODS: In the German-language CEDATA-GPGE registry, 3991 cases of IBD in patients less than 18 years of age were documented from 2004 to 2014. The 1257 patients who were prospectively included in the registry upon diagnosis and whose further course was documented for at least three months were analyzed in two separate groups--under 10 years old, and 10 years and above--with respect to the type and duration of their symptoms until diagnosis, the completeness of the diagnostic evaluation, the disease phenotype, and the initial treatment. RESULTS: Of the 958 patients for whom full documentation was available, 616 (64.3%) had Crohn's disease (CD), 278 (29%) had ulcerative colitis (UC), 64 (6.7%) had an unclassified IBD, and 23.2% were under 10 years old. The latency to diagnosis was longer for CD than for UC (0.5 versus 0.3 years), regardless of age. 62.5% of the CD patients had ileocolonic involvement, and more than half had involvement of the upper gastrointestinal tract. 71% of the patients with UC had subtotal colitis or pancolitis. Continuous improvement was seen in diagnostic assessment according to published guidelines. For example, in 2004/2005, 69% of patients were evaluated endoscopically with ileocolonoscopy and esophagogastroduodenoscopy; this fraction had risen to nearly 100% by 2013/2014. Similarly, the percentage of patients who underwent a diagnostic evaluation of the small intestine, as recommended, rose from 41.2% to 60.9% over the same period. The most common initial treatments were 5- amino - salicylates (86.8% CD, 100% UC) and glucocorticoids (60.6% CD, 65.6% UC). 32% of the patients with CD received exclusive enteral nutrition therapy. CONCLUSION: Most of these pediatric patients with IBD, whether in the younger or the older age group, had extensive bowel involvement at the time of diagnosis. The registry data imply that improvement in clinical course may be achieved by shortening the time to diagnosis and by closer adherence to the diagnostic and therapeutic guidelines.

Air kerma to dose equivalent conversion coefficients not included in ISO 4037-3.

The International Organization for Standardization (ISO) has issued a standard series on photon reference radiation qualities (ISO 4037). In this work, conversion coefficients from air kerma to dose equivalent quantities not included in ISO 4037-3 are supplied for the following quantities: For H(p)(0.07) for X and gamma radiation qualities for the rod, the pillar and the slab phantom and for H(p)(3) for X and gamma radiation qualities for the slab phantom. In addition, an overview of conversion coefficients suggested for use for all quantities relevant in radiation protection is provided.

Childhood onset inflammatory bowel disease: predictors of delayed diagnosis from the CEDATA German-language pediatric inflammatory bowel disease registry.

OBJECTIVES: To examine predictors of delayed diagnosis of inflammatory bowel disease in children and adolescents. STUDY DESIGN: A total of 2,436 patients (age 0-18 years) with Crohn's disease, ulcerative colitis, or unclassified colitis were included from 53 pediatric gastroenterologists. Predictors were examined with the proportional hazards model, presented as hazard ratios (HR) with 95% confidence intervals. HR < 1.0 represent factors associated with late diagnosis. RESULTS: Median time to diagnosis was 4 (2-8) months. Crohn's disease (HR 0.62; 0.56-0.68), and within Crohn's disease, ileal disease (HR 0.77, 95% confidence interval 0.67 to 0.89) were associated with delayed diagnosis. Chances for early diagnosis increased with increasing age (HR 1.07 per year of age; 1.06 to 1.08). There was also an effect by center (HR 0.63, 0.52 to 0.67), but not by sex or country (Austria vs Germany). Growth failure was more common in those cases with delayed diagnosis. CONCLUSIONS: There is still concern about delays in the diagnosis of inflammatory bowel disease in the very young and in children with small bowel disease. Inequalities of care by region require further investigation.

Re-treatment of children with chronic hepatitis C who did not respond to interferon-alpha treatment.

BACKGROUND: Many patients with chronic hepatitis C do not respond to antiviral treatment. In adult patients the re-treatment of these patients has been extensively investigated. Because the response to re-treatment in children is not well defined we evaluated the efficacy and safety of interferon (IFN)-alpha plus ribavirin in patients who have failed to respond to previous treatment. PATIENTS AND METHODS: In an open-label, uncontrolled study, 18 chronically infected children were investigated. Fifteen children had been treated with IFN-alpha plus ribavirin and 3 patients with IFN-alpha alone. Fourteen patients were nonresponders; 4 experienced viral breakthrough during treatment and/or relapse after treatment. Patients received IFN-alpha 3 times per week subcutaneously plus ribavirin for 48 weeks. Sixteen patients were infected with hepatitis C virus (HCV) genotype 1, 2 with genotype 4, and 1 with genotype 3 and co-infection with hepatitis B. RESULTS: Four patients showed early viral response to therapy and became HCV-RNA negative after 12 weeks. Sustained viral response (HCV-RNA negative 6 months after end of treatment) was documented in 2 of them. These 2 patients belonged to the group of 4 children who relapsed or experienced a viral breakthrough during previous treatment. None of the 14 patients with prior nonresponse had sustained viral response. CONCLUSIONS: Re-treatment with IFN-alpha plus ribavirin may be useful in children who relapsed in a previous antiviral treatment but seems not to be useful in nonresponders. These results are in line with studies from adult patients and should be therefore encouraged to provide a second chance for healing in a subgroup of patients.

Growth failure in children and adolescents with Crohn's disease.

BACKGROUND/AIMS: A clinical analysis in children, adolescents and young adults with Crohn's disease was performed to investigate if growth failure is caused by an impaired growth hormone secretion in these patients. METHODS: 40 patients with Crohn's disease (26 male, 14 female) with an average age of 16,7 years (median: 17,0 years, range: 4-29) were included in the study. The observation period varied from 8 months to 16,7 years, patient's age ranged from 4 years up to 29 years. To examine growth hormone excretion, urinary growth hormone was measured using an in vitro immunoradiometric assay in three morning urine samples. Renal function was obtained by analysing creatinine and alpha-1-microglobulin in the same samples. Observation period, chronological age, height, growth rate, pubertal stage, localisation, pediatric Crohn disease activity index and corticosteroid treatment as well as IGF-1 levels were determined. We found normal urinary growth hormone levels in Crohn's disease concluding that growth failure in patients with Crohn's disease is not caused by growth hormone deficiency. Evenly corticosteroid therapy did not appear to be the most responsible factor for growth failure in Crohn's disease. CONCLUSIONS: Disease activity indicated by a high pediatric Crohn disease activity index score had an important impact on impaired growth in children and adolescents with Crohn's disease.

Influence of percutaneous endoscopic gastrostomy on gastroesophageal reflux: a prospective study in 68 children.

BACKGROUND: Among other complications, the development of or an increase of gastroesophageal reflux (GER) is considered to be associated with percutaneous endoscopic gastrostomy (PEG). However, the few studies performed to date show controversial results. METHODS: Continuous 24-hour pH monitoring was performed prospectively in 68 patients before and at least 3 days after percutaneous endoscopic gastrostomy placement. None of the patients had been treated for gastroesophageal reflux. RESULTS: The percentage of patients with abnormal test results did not differ significantly before and after PEG insertion (22.1% versus 25%). Nor did the median reflux index change significantly before and after gastrostomy for the whole group of patients (2.6% versus 3.4%). The median reflux index increased significantly (from 1.8 to 5.4) only in patients who underwent PEG implantation in the antrum (n = 9). Clinical signs of GER correlated poorly with the results of pH monitoring. CONCLUSIONS: Data in this study strongly suggest that, in general, percutaneous endoscopic gastrostomy does not provoke gastroesophageal reflux. Results also indicate that placement in the antrum may be unfavorable.

"Mowat-Wilson" syndrome with and without Hirschsprung disease is a distinct, recognizable multiple congenital anomalies-mental retardation syndrome caused by mutations in the zinc finger homeo box 1B gene.

Recently mutations in the gene ZFHX1B (SIP1) were shown in patients with "syndromic Hirschsprung disease" with mental retardation (MR) and multiple congenital anomalies (MCA), but it was unclear if Hirschsprung disease is an obligate symptom of these mutations and if the distinct facial phenotype delineated by Mowat et al. [1998: J Med Genet 35: 617-623] is specific for ZFHX1B mutations. In order to address these open questions we analyzed the ZFHX1B gene in five patients, three of whom had "syndromic Hirschsprung disease" two with and one without the facial phenotype described by Mowat et al. [1998], and two of whom had the distinct facial gestalt without Hirschsprung disease. Analyses of microsatellite markers and newly identified SNPs, and/or FISH with BACs from the ZFHX1B region excluded large deletions in all five patients. Direct sequencing demonstrated truncating ZFHX1B mutations in all four patients with the characteristic facial phenotype, but not in the patient with syndromic Hirschsprung disease without the distinct facial appearance. We demonstrate that there is a specific clinical entity with a recognizable facial gestalt, mental retardation and variable MCAs which we propose be called the "Mowat-Wilson syndrome."