Prevalence, serogroup distribution and risk factors of Neisseria meningitidis carriage in high school and university students in Hungary.

Neisseria meningitidis causes life-threatening invasive meningococcal disease (IMD) with high mortality worldwide. Asymptomatic pharyngeal meningococcus colonisation is an important reservoir for the spread of the bacterium. The aim of this study was to determine N. meningitidis colonisation rates in asymptomatic high school and university students and to identify risk factors for carriage. Oropharyngeal swab samples and data from a self-reported questionnaire were obtained from overall 610 students, among them 303 university students and 307 high school students, aged between 15 and 31 years in Budapest, Hungary, between November 2017 and December 2018. Meningococcal carriage and serogroup of N. meningitidis were determined by RT-PCR from DNA extracted directly from the specimen. N. meningitidis was identified in 212 (34.8 %) of the participants. Significantly higher carriage rate was found among high school students (48.9 %) compared to university students (20.5 %). Peak of colonisation rate was among 17-19-year-old students (48.7 %). Most carriage isolates were non-typable (87.3 %). From the 212 meningococcus carriers, 19 were colonised by serogroup B (9 %), 5 by serogroup C (2.4 %), and 1 had serogroup Y (0.5 %). Significantly higher colonisation rate was found among males (42.4 %) than in females (33.1 %). Antibiotic use in the past 2 months has decreased the rate of meningococcal colonisation. Recent respiratory infection, active or passive smoking and attending parties have not influenced meningococcal colonisation rate significantly. In conclusion, we have found high asymptomatic meningococcus carriage rate among high school students and young adults, however, the majority of the colonizing meningococci were non-typable.

Gastrointestinal Comorbidities Associated with Atopic Dermatitis-A Narrative Review.

The current understanding of atopic dermatitis (AD) seems to be extending beyond a skin-confined condition frequently associated with allergic comorbidities, as in a number of epidemiological studies, the prevalence rate of a range of illnesses has been determined to be greater in patients with AD, or inversely. In most cases, the reasons for this are vague. A subset of these conditions are gastrointestinal disorders, including food sensitization (FS) and food allergy (FA), eosinophilic esophagitis (EoE) (it is of mixed background, both IgE-dependent and independent), food protein-induced enterocolitis syndrome (FPIES) (it exemplifies an IgE-independent food allergy), Crohn's disease (CD), colitis ulcerosa (CU), celiac disease, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD). In this review, we performed a comprehensive search of the literature using the PubMed database. We addressed the epidemiology of the increased co-occurrence of these diseases with AD and discussed potential causes for this subject. Multiple gastroenterological comorbidities appear to be more common in patients with AD, according to our review. The mechanisms that underlie this phenomenon are largely unknown, highlighting the need for further study in this field.

Plasma arginine metabolites in health and chronic kidney disease.

BACKGROUND: Elevated plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) are risk factors for chronic kidney disease (CKD) and cardiovascular disease. Using plasma cystatin C (pCYSC)-based estimated glomerular filtration rate (eGFR) trajectories, we identified a cohort at high risk of poor kidney-related health outcomes amongst members of the Dunedin Multidisciplinary Health and Development Study (DMHDS). We therefore examined associations between methylarginine metabolites and kidney function in this cohort. METHODS: ADMA, SDMA, L-arginine and L-citrulline were measured in plasma samples from 45-year-olds in the DMHDS cohort by liquid chromatography-tandem mass spectrometry. RESULTS: In a healthy DMHDS subset (n = 376), mean concentrations were: ADMA (0.40 ± 0.06 µmol/L), SDMA (0.42 ± 0.06 µmol/L), L-arginine (93.5 ± 23.1 µmol/L) and L-citrulline (24.0 ± 5.4 µmol/L). In the total cohort (n = 857), SDMA correlated positively with serum creatinine (Pearson's r = 0.55) and pCYSC (r = 0.55), and negatively with eGFR (r = 0.52). A separate cohort of 38 patients with stage 3-4 CKD (eGFR 15-60 mL/min/1.73 m2) confirmed significantly higher mean ADMA (0.61 ± 0.11 µmol/L), SDMA (0.65 ± 0.25 µmol/L) and L-citrulline (42.7 ± 11.8 µmol/L) concentrations. DMHDS members classified as high-risk of poor kidney health outcomes had significantly higher mean concentrations of all four metabolites compared with individuals not at risk. ADMA and SDMA individually predicted high-risk of poor kidney health outcomes with areas under the ROC curves (AUCs) of 0.83 and 0.84, and together with an AUC of 0.90. CONCLUSIONS: Plasma methylarginine concentrations facilitate stratification for risk of CKD progression.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XIII - Oral immunotherapy for CMA - Systematic review.

Background: Allergy to cow's milk is the most common food allergy in infants and it is usually outgrown by 5 years of age. In some individuals it persists beyond early childhood. Oral immunotherapy (OIT, oral desensitization, specific oral tolerance induction) has been proposed as a promising therapeutic strategy for persistent IgE-mediated cow's milk allergy. We previously published the systematic review of OIT for cow's milk allergy (CMA) in 2010 as part of the World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guidelines. Objective: To systematically synthesize the currently available evidence about OIT for IgE-mediated CMA and to inform the updated 2022 WAO guidelines. Methods: We searched the electronic databases including PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and the websites of selected allergy organizations. We included all studies irrespective of the language of the original publication. The last search was conducted in February 2021. We registered the protocol on Open Science Framework (10.17605/OSF.IO/AH2DT). Results: We identified 2147 unique records published between 2010 and 2021, including 13 randomized trials and 109 observational studies addressing cow's milk OIT. We found low-certainty evidence that OIT with unheated cow's milk, compared to elimination diet alone, increased the likelihood of being able to consume ≥150 ml of cow's milk in controlled settings (risk ratio (RR): 12.3, 95% CI: 5.9 to 26.0; risk difference (RD): 25 more per 100, 95% CI 11 to 56) as well as accidently ingest a small amount (≥5 ml) of cow's milk (RR: 8.7, 95% CI: 4.7 to 16.1; RD: 25 more per 100, 95% CI 12 to 50). However, 2-8 weeks after discontinuation of a successful OIT, tolerance of cow's milk persisted in only 36% (range: 20%-91%) of patients. OIT increased the frequency of anaphylaxis (rate ratio: 60.0, 95% CI 15 to 244; rate difference 5 more anaphylactic reactions per 1 person per year, 95% CI: 4 to 6; moderate evidence) and the frequency of epinephrine use (rate ratio: 35.2, 95% CI: 9 to 136.5; rate difference 268 more events per 100 person-years, 95% CI: 203 to 333; high certainty). OIT also increased the risk of gastrointestinal symptoms (RR 6.9, 95% CI 1.6-30.9; RD 28 more per 100, CI 3 to 100) and respiratory symptoms (RR 49.0, 95% CI 3.12-770.6; RD 77 more per 100, CI 62 to 92), compared with avoidance diet alone. Single-arm observational studies showed that on average 6.9% of OIT patients (95% CI: 3.8%-10%) developed eosinophilic esophagitis (very low certainty evidence). We found 1 trial and 2 small case series of OIT with baked milk. Conclusions: Moderate certainty evidence shows that OIT with unheated cow's milk in patients with IgE-mediated CMA is associated with an increased probability of being able to drink milk and, at the same time, an increased risk of serious adverse effects.

Sodium Picosulphate with Magnesium Citrate versus Polyethylene Glycol for Bowel Preparation in Children: A Systematic Review.

Purpose: To compare the effectiveness, tolerability, acceptability, and safety of sodium picosulphate with magnesium citrate (PS/Mg) and polyethylene glycol (PEG) in children (≤18 years) preparing for colonoscopy. Methods: Three electronic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) were searched till July 2020. Only randomized controlled trials (RCTs) were included. At least two authors independently selected studies and performed risk of bias assessment and data extraction. Results: Four RCTs (n=390), with overall good quality were included. A meta-analysis of two trials (n=224) found no statistically significant difference between the groups with respect to the proportion of patients who had excellent and good scores (≥6 points) according to the Boston Bowel Preparation Scale (relative risk: 0.99; 95% confidence interval [CI]: 0.90 to 1.08). Excellent and good scores were observed in both groups in approximately 90% of children. A meta-analysis of two other trials (n=150) showed no significant difference between the groups with respect to the mean total score for the Ottawa Bowel Preparation Scale (mean difference: 0.20; 95% CI: -0.74 to 1.14). Both regimens provided a comparable safety profile; however, PS/Mg was significantly superior to high volume PEG in terms of tolerability (abdominal pain, nausea, vomiting, bloating/flatulence/fullness) and acceptability (ease of formulation consumption, taste acceptance, need for nasogastric tube, compliance with full dose). Conclusion: PS/Mg provides a quality and safety profile similar to PEG for bowel cleansing; however, it has better acceptance and tolerance in children preparing for colonoscopy.

Harmonization of LC-MS/MS Measurements of Plasma Free Normetanephrine, Metanephrine, and 3-Methoxytyramine.

BACKGROUND: Plasma-free normetanephrine and metanephrine (metanephrines) are the recommended biomarkers for testing of pheochromocytoma and paraganglioma (PPGL). This study evaluated the status of harmonization of liquid chromatography-tandem mass spectrometry-based measurements of plasma metanephrines and methoxytyramine and clinical interpretation of test results. METHODS: 125 plasma samples from patients tested for PPGLs were analyzed in 12 laboratories. Analytical performance was also assessed from results of a proficiency-testing program. Agreement of test results from different laboratories was assessed by Passing-Bablok regression and Bland-Altman analysis. Agreement in clinical test interpretation based on laboratory specific reference intervals was also examined. RESULTS: Comparisons of analytical test results by regression analysis revealed strong correlations for normetanephrine and metanephrine (R ≥ 0.95) with mean slopes of 1.013 (range 0.975-1.078), and 1.019 (range 0.963-1.081), and intercepts of -0.584 (-53.736 to 54.790) and -3.194 (-17.152 to 5.933), respectively. The mean bias between methods was 1.2% (-11.6% to 16.0%) for metanephrine and 0.1% (-18.0% to 9.5%) for normetanephrine. Measurements of 3-methoxytyramine revealed suboptimal agreement between laboratories with biases ranging from -32.2% to 64.0%. Interrater agreement in test interpretation was >94% for metanephrine and >84% for normetanephrine; improvements in interrater agreement were observed with use of harmonized reference intervals, including age-specific cut-offs for normetanephrine. CONCLUSIONS: Analytical methods for metanephrines are well harmonized between laboratories. However, the 16% disagreement in test interpretation for normetanephrine suggests use of suboptimal method-dependent reference intervals for clinical decision-making for this metabolite. Improved analytical methods and reference interval harmonization are particularly required for 3-methoxytyramine.

Reference intervals for venous blood gas measurement in adults.

OBJECTIVES: Venous blood gas (VBG) analysis is becoming a popular alternative to arterial blood gas (ABG) analysis due to reduced risk of complications at phlebotomy and ease of draw. In lack of published data, this study aimed to establish reference intervals (RI) for correct interpretation of VBG results. METHODS: One hundred and 51 adult volunteers (101 females, 50 males, 18-70 years) were enrolled after completion of a health questionnaire. Venous blood was drawn into safePICO syringes and analysed on ABL827 blood gas analyser (Radiometer Pacific Pty. Ltd.). A non-parametric approach was used to directly establish the VBG RI which was compared to a calculated VBG RI based on a meta-analysis of differences between ABG and VBG. RESULTS: After exclusions, 134 results were used to derive VBG RI: pH 7.30-7.43, partial pressure of carbon dioxide (pCO2) 38-58 mmHg, partial pressure of oxygen (pO2) 19-65 mmHg, bicarbonate (HCO3-) 22-30 mmol/L, sodium 135-143 mmol/L, potassium 3.6-4.5 mmol/L, chloride 101-110 mmol/L, ionised calcium 1.14-1.29 mmol/L, lactate 0.4-2.2 mmol/L, base excess (BE) -1.9-4.5 mmol/L, saturated oxygen (sO2) 23-93%, carboxyhaemoglobin 0.4-1.4% and methaemoglobin 0.3-0.9%. The meta-analysis revealed differences between ABG and VBG for pH, HCO3-, pCO2 and pO2 of 0.032, -1.0 mmol/L, -4.2 and 39.9 mmHg, respectively. Using this data along with established ABG RI, calculated VBG RI of pH 7.32-7.42, HCO3- 23 - 27 mmol/L, pCO2 36-49 mmHg (female), pCO2 39-52 mmHg (male) and pO2 43-68 mmHg were formulated and compared to the VBG RI of this study. CONCLUSIONS: An adult reference interval has been established to assist interpretation of VBG results.

Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial.

PURPOSE: Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer commonly driven by the Merkel cell polyomavirus (MCPyV). The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive pathway is often upregulated in MCC, and advanced metastatic MCC frequently responds to PD-1 blockade. We report what we believe to be the first trial of anti-PD-1 in the neoadjuvant setting for resectable MCC. METHODS: In the phase I/II CheckMate 358 study of virus-associated cancer types, patients with resectable MCC received nivolumab 240 mg intravenously on days 1 and 15. Surgery was planned on day 29. Tumor regression was assessed radiographically and microscopically. Tumor MCPyV status, PD-L1 expression, and tumor mutational burden (TMB) were assessed in pretreatment tumor biopsies. RESULTS: Thirty-nine patients with American Joint Committee on Cancer stage IIA-IV resectable MCC received ≥ 1 nivolumab dose. Three patients (7.7%) did not undergo surgery because of tumor progression (n = 1) or adverse events (n = 2). Any-grade treatment-related adverse events occurred in 18 patients (46.2%), and grade 3-4 events in 3 patients (7.7%), with no unexpected toxicities. Among 36 patients who underwent surgery, 17 (47.2%) achieved a pathologic complete response (pCR). Among 33 radiographically evaluable patients who underwent surgery, 18 (54.5%) had tumor reductions ≥ 30%. Responses were observed regardless of tumor MCPyV, PD-L1, or TMB status. At a median follow-up of 20.3 months, median recurrence-free survival (RFS) and overall survival were not reached. RFS significantly correlated with pCR and radiographic response at the time of surgery. No patient with a pCR had tumor relapse during observation. CONCLUSION: Nivolumab administered approximately 4 weeks before surgery in MCC was generally tolerable and induced pCRs and radiographic tumor regressions in approximately one half of treated patients. These early markers of response significantly predicted improved RFS. Additional investigation of these promising findings is warranted.

Effects of prenatal and/or postnatal supplementation with iron, PUFA or folic acid on neurodevelopment: update.

Neurodevelopment has been linked, among other factors, to maternal and early infant diets. The objective of this review, which is part of the NUTRIMENTHE research project 'The effect of diet on the mental performance of children' (www.nutrimenthe.com), was to update current evidence on the effects of nutritional interventions such as iron, folic acid or n-3 long-chain polyunsaturated fatty acid (LCPUFA) supplementation during pregnancy and/or in early life on the mental performance and psychomotor development of children. In May 2014, we searched MEDLINE and The Cochrane Database of Systematic Reviews for relevant studies published since 2009. The limited updated evidence suggests that iron supplementation of infants may positively influence the psychomotor development of children, although it does not seem to alter their mental development or behaviour. The use of multivitamin-containing folic acid supplements during pregnancy did not benefit the mental performance of the offspring. Evidence from randomised controlled trials (RCT) did not show a clear and consistent benefit of n-3 LCPUFA supplementation during pregnancy and/or lactation on childhood cognitive and visual development. Caution is needed when interpreting current evidence, as many of the included trials had methodological limitations such as small sample sizes, high attrition rates, and no intention-to-treat analyses. Taken together, the evidence is still inconclusive. Large, high-quality RCT to assess the effects of supplementation with iron, LCPUFA or folic acid are still needed to further clarify the effects of these, and other nutrients, on neurodevelopment. Recent recommendations from scientific societies are briefly presented.

Combined iron oxide nanoparticle ferumoxytol and gadolinium contrast enhanced MRI define glioblastoma pseudoprogression.

BACKGROUND: Noninvasively differentiating therapy-induced pseudoprogression from recurrent disease in patients with glioblastoma is prospectively difficult due to the current lack of a biologically specific imaging metric. Ferumoxytol iron oxide nanoparticle MRI contrast characterizes innate immunity mediated neuroinflammation; therefore, we hypothesized that combined ferumoxytol and gadolinium enhanced MRI could serve as a biomarker of glioblastoma pseudoprogression. METHODS: In this institutional review board-approved, retrospective study, we analyzed ferumoxytol and gadolinium contrast enhanced T1-weighted 3T MRI in 45 patients with glioblastoma over multiple clinical timepoints. Isocitrate dehydrogenase 1 (IDH-1) mutational status was characterized by exome sequencing. Sum of products diameter measurements were calculated according to Response Assessment in Neuro-Oncology criteria from both gadolinium and ferumoxytol enhanced sequences. Enhancement mismatch was calculated as the natural log of the ferumoxytol to gadolinium sum of products diameter ratio. Analysis of variance and Student's t-test assessed differences in mismatch ratios. P-value <0.05 indicated statistical significance. RESULTS: With the development of pseudoprogression we observed a significantly elevated mismatch ratio compared with disease recurrence (P < 0.01) within IDH-1 wild type patients. Patients with IDH-1 mutation demonstrated significantly reduced mismatch ratio with the development of pseudoprogression compared with disease recurrence (P < 0.01). Receiver operator curve analysis demonstrated 100% sensitivity and specificity for the use of mismatch ratios as a diagnostic biomarker of pseudoprogression. CONCLUSION: Our study suggests that ferumoxytol to gadolinium contrast mismatch ratios are an MRI biomarker for the diagnosis of pseudoprogression in patients with glioblastoma. This may be due to the unique characterization of therapy-induced neuroinflammation.

Cerebral blood volume mapping with ferumoxytol in dynamic susceptibility contrast perfusion MRI: Comparison to standard of care.

BACKGROUND: Cerebral blood volume (CBV) mapping with a dynamic susceptibility contrast (DSC) perfusion technique has become a clinical tool in diagnosing and follow-up of brain tumors. Ferumoxytol, a long-circulating iron oxide nanoparticle, has been tested for CBV mapping, but the optimal dose has not been established. PURPOSE: To compare ferumoxytol DSC of two different doses to standard of care gadoteridol by analyzing time-intensity curves and CBV maps in normal-appearing brain regions. STUDY TYPE: Retrospective. SUBJECTS: Fifty-four patients with various brain disorders. FIELD STRENGTH/SEQUENCE: 3T MRI. DSC-MRI was performed with 0.1 mmol/kg gadoteridol and 1 day later with ferumoxytol in doses of 1 or 2 mg/kg. ASSESSMENT: Signal changes during first pass, relative CBV (rCBV) in normal-appearing thalamus, putamen, and globus pallidus, and contrast-to-noise ratio (CNR) of the CBV maps were compared between gadoteridol and various doses of ferumoxytol using an automated method. To subjectively assess the quality of the CBV maps, two blinded readers also assessed visual conspicuity of the putamen. STATISTICAL TESTS: Linear mixed effect model was used for statistical comparison. RESULTS: Compared to gadoteridol, 1 mg/kg ferumoxytol showed no difference in CNR (P = 0.6505), peak ΔR2*, and rCBV in the putamen (P = 0.2669, 0.0871) or in the thalamus (P = 0.517, 0.9787); 2 mg/kg ferumoxytol increased peak ΔR2* as well as the CNR (P < 0.0001), but also mildly increased rCBV in putamen and globus pallidus (P = 0.0005, 0.0012). Signal intensities during first pass remained highly above the noise level, with overlapping of 95% confidence intervals with noise only in 3 out of 162 tested regions. Compared to gadoteridol, the visual image quality showed mild improvement with 1 mg/kg (P = 0.02) and marked improvement with 2 mg/kg ferumoxytol (P < 0.0001). DATA CONCLUSION: 1 mg/kg ferumoxytol provides similar imaging results to standard gadoteridol for DSC-MRI, and 2 mg/kg has a benefit of increased CNR, but may also result in mildly increased rCBV values. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:441-448.

Quantitative comparison of delayed ferumoxytol T1 enhancement with immediate gadoteridol enhancement in high grade gliomas.

PURPOSE: Delayed ferumoxytol enhancement on T1 -weighted images appears visually similar to gadoteridol enhancement. The purpose of this study was to quantitatively compare ferumoxytol T1 enhancement to gadoteridol enhancement with an objective, semi-automated method. METHODS: 206 sets of post-gadoteridol and 24 h post-ferumoxytol T1 -weighted scans from 58 high grade glioma patients were analyzed (9 pre-chemoradiation, 111 < 90 days post-chemoradiation, 21 > 90 days post-chemoradiation, 65 post-bevacizumab scans). Enhancement volumes and signal intensities normalized to normal appearing tissue proximal to enhancement were calculated with a semi-automated method. Enhancement cube root volumes (D) and signal intensities (SI) were compared between the 2 contrast agents, and relative difference of D and SI were compared in different treatment groups with multivariate analysis. Within patient differences in D and SI before and after treatment with bevacizumab or steroid were assessed in 26 patients in each treatment group. RESULTS: When compared to gadoteridol, ferumoxytol D was 13.83% smaller and SI was 7.24% lower (P < 0.0001). The relative differences in D and SI between the 2 contrast agents were not significantly different between treatment groups (P > 0.05). Relative difference in D and SI did not change significantly in response to bevacizumab (P = 0.5234 and P = 0.2442, respectively) or to steroid (P = 0.3774, P = 0.0741) in the within patient comparison. CONCLUSION: The correlation between the 2 contrast agents' enhancement size and signal intensity and their similar behavior in response to therapy suggest that ferumoxytol can be used for revealing enhancement in high grade glioma patients. Magn Reson Med 80:224-230, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Current and potential imaging applications of ferumoxytol for magnetic resonance imaging.

Contrast-enhanced magnetic resonance imaging is a commonly used diagnostic tool. Compared with standard gadolinium-based contrast agents, ferumoxytol (Feraheme, AMAG Pharmaceuticals, Waltham, MA), used as an alternative contrast medium, is feasible in patients with impaired renal function. Other attractive imaging features of i.v. ferumoxytol include a prolonged blood pool phase and delayed intracellular uptake. With its unique pharmacologic, metabolic, and imaging properties, ferumoxytol may play a crucial role in future magnetic resonance imaging of the central nervous system, various organs outside the central nervous system, and the cardiovascular system. Preclinical and clinical studies have demonstrated the overall safety and effectiveness of this novel contrast agent, with rarely occurring anaphylactoid reactions. The purpose of this review is to describe the general and organ-specific properties of ferumoxytol, as well as the advantages and potential pitfalls associated with its use in magnetic resonance imaging. To more fully demonstrate the applications of ferumoxytol throughout the body, an imaging atlas was created and is available online as supplementary material.

Efficacy and Safety of Adalimumab for Paediatric Crohn's Disease: A Systematic Review.

BACKGROUND AND AIM: Adalimumab is well-established therapy for adults with Crohn's disease [CD]. The aim of the study was to systematically assess the published evidence on the efficacy and safety of adalimumab for Crohn's disease in children. METHODS: MEDLINE, EMBASE, the Cochrane Library, and abstracts from the main gastroenterological meetings in the past 5 years were systematically searched up to July 2015 for randomised controlled trials and observational studies on the efficacy and safety of adalimumab for Crohn's treatment in children and adolescents. RESULTS: A total of 14 studies [1 randomised controlled trial, 13 case series], altogether including 664 patients [age: 1.9 to 21 years] were available for analysis. The studies differed with respect to patients' characteristics, including percentage of infliximab-naïve patients, disease duration, site of the disease, adalimumab doses, treatment duration, and follow-up period. The pooled remission rates were: 30% [n = 93/309] at 4 weeks, 54% [n = 79/145] at 3 months, 45% [n = 18/40] at 4 months, 42% [n = 146/345] at 6 months, 57% [n = 20/35] at 8 months, and 44% [n = 169/383] at 12 months. Of the total patients, 6% [n = 13/207] were classified as primary non-responders and 12% [n = 69/599] had severe adverse events reported including 2 deaths and 1 medulloblastoma. Withdrawal rate due to adverse events reported in one study was 35% [n = 64/182]. CONCLUSION: According to low-quality evidence based mainly on case series, approximately half of children with Crohn's disease on adalimumab therapy achieve remission during the first year of the therapy with reasonable safety profile. There is still a need for high-quality evidence on effectiveness and safety of adalimumab for paediatric Crohn's disease.

Biexponential diffusion alterations in the normal-appearing white matter of glioma patients might indicate the presence of global vasogenic edema.

PURPOSE: To investigate normal-appearing white matter (NAWM) microstructure of glioma patients with biexponential diffusion analysis in order to reveal the nature of diffusion abnormalities and to assess whether they are region-specific or global. MATERIALS AND METHODS: Twenty-four newly diagnosed glioma patients (grade II-IV) and 24 matched control subjects underwent diffusion-weighted imaging at 3T. Diffusion parameters were calculated using monoexponential and biexponential models. Apparent diffusion coefficient (ADC) values were measured in the entire NAWM of the hemisphere contralateral and ipsilateral to the tumor. In the contralateral NAWM, regional ADC values were assessed in the frontal, parietal, occipital, and temporal NAWM. RESULTS: ADCmono and ADCfast were significantly higher than control values in all investigated regions except the temporal NAWM (P < 0.04). ADCslow was significantly increased in the total contralateral, frontal, and parietal NAWM (P < 0.03), while pslow was decreased in both total hemispheric NAWM and the parietal NAWM of glioma patients compared to controls (P < 0.04). ADCmono , ADCfast , ADCslow , and pslow were significantly different among the NAWM of the four lobes of the contralateral hemisphere in both groups (P < 0.0001), and these regional differences were similar in patients and controls (P > 0.05). Hemispheric ADCmono and pslow differences were different between groups (P < 0.05). CONCLUSION: Globally altered diffusion parameters suggest the presence of global vasogenic edema in the NAWM of glioma patients, which is further supported by the finding that regional differences in patients follow those found in controls. Alternatively, some tumor infiltration might contribute to diffusion abnormalities in the NAWM, especially in the tumor-affected hemisphere. J. Magn. Reson. Imaging 2016;44:633-641.

Increased diffusion in the normal appearing white matter of brain tumor patients: is this just tumor infiltration?

Altered diffusion in the normal appearing white matter (NAWM) of glioma patients has been explained by tumor infiltration. The goal of the present study was to test this explanation indirectly by examining whether these alterations were also present in the contralateral NAWM of non-infiltrative tumors like meningiomas; and to search for other possible reasons for this abnormality. Twenty-seven patients with histologically verified glioma (grade II-IV), 22 meningioma patients and two groups of age- and sex-matched healthy controls underwent diffusion weighted imaging (DWI) on a 3T MR. All patients were examined before treatment. Apparent diffusion coefficient (ADC) values were calculated in the entire NAWM of the hemisphere contralateral to the tumor. ADC values of the NAWM were compared between groups with Mann-Whitney U-test and multiple linear regression. The relations of ADC in NAWM to glioma grade and to tumor volume were also investigated. ADC values of the contralateral NAWM were significantly higher in both glioma and meningioma patients compared to controls (P = 0.0006 and 0.0099, respectively). ADC value was higher in the NAWM of high grade gliomas than in low grade gliomas (P = 0.0181) and in healthy control subjects (P = 0.0003). ADC did not depend on tumor volume in any of the patient groups. Elevated ADC in the NAWM of both glioma and meningioma patients might indicate that the effect of infiltrating tumor cells is not the only reason for the alteration as it has been previously suggested. Although the role of mass effect was not proved, other mechanisms might also contribute to ADC elevation.

MULTIMODAL QUANTITATIVE CHARACTERIZATION OF INTRACRANIAL EPIDERMOID CYSTS: PRELIMINARY RESULTS.

BACKGROUND AND PURPOSE: The differentiation of epidermoid cysts from other intracranial lesions with CT and conventional MR imaging is challenging. The risk of residual and recurrent disease is high and multimodal imaging should therefore promote a precise differential diagnosis. Since epidermoid cysts are histologically identical to middle ear cholesteatomas, MRI methods that are useful in the diagnosis of cholesteatoma; specifically EPI DWI and a non-EPI diffusion subtype (HASTE DWI) may possibly be applicable to epidermoid cysts. Besides testing the diagnostic utility of these methods on epidermoid cysts, our goal was to quantify the T1 and T2 relaxation times, the ADC values and the magnetization transfer ratios in order to acquire objective, characteristic information about their structure and contents. Finally, our goal was to provide the physician with a reliable, multimodal diagnostic tool that supports accurate surgical planning. METHODS: Two patients with epidermoid cysts were examined. Besides the conventional MR scans EPI DWI, HASTE DWI, quantitative T1, T2 and magnetization transfer measurements were performed mappingwith a 3T MR scanner. After image registration, T1, T2 relaxation times and the magnetization transfer ratio inside a ROI were determined according to the lesion location on HASTE DWI. Mean ADC values inside the epidermoid cysts were also calculated by both mono-exponential and bi-exponential diffusion models. RESULTS: Our results revealed relatively high T1 and T2 relaxation times and ADC values, and low magnetization transfer ratios in both subjects. CONCLUSION: HASTE-DW MRI provides accurate morphologic information on epidermoid cysts, while T1, T2, ADC and magnetization transfer ratio maps are quantitative techniques. Thus the combination of these methods results in a confident preoperative diagnosis and aids to determine the indication of retreatment in the event of recurrence.

Quantitative assessment of brain iron by R2* relaxometry in patients with cervical dystonia.

BACKGROUND: The pathophysiology of cervical dystonia is poorly understood. Increased brain iron deposition has been described in different movement disorders. Our aim was to investigate brain iron content in patients with cervical dystonia, using R2* relaxation rate, a validated MRI marker of brain iron level. METHODS: Twelve female patients with primary focal cervical dystonia (mean age: 45.4 ± 8.0 years) and 12 age-matched healthy female subjects (mean age: 45.0 ± 8.0 years) underwent 3T MRI to obtain regional R2* relaxation rates of the thalamus, caudate nucleus, putamen, and globus pallidus (GP). Regions of interest were delineated automatically on T1-weighted MRIs. RESULTS: R2* values in the putamen were positively correlated with age. Patients with cervical dystonia showed elevated R2* values in the GP. CONCLUSIONS: This pilot study provides the first quantitative support for increased brain iron deposition in cervical dystonia. Further studies are needed to explore the implications of this finding.