Intracerebral gadolinium deposition following blood-brain barrier disturbance in two different mouse models.

To evaluate the influence of the blood-brain barrier on neuronal gadolinium deposition in a mouse model after multiple intravenous applications of the linear contrast agent gadodiamide. The prospective study held 54 mice divided into three groups: healthy mice (A), mice with iatrogenic induced disturbance of the blood-brain barrier by glioblastoma (B) or cerebral infarction (C). In each group 9 animals received 10 iv-injections of gadodiamide (1.2 mmol/kg) every 48 h followed by plain T1-weighted brain MRI. A final MRI was performed 5 days after the last contrast injection. Remaining mice underwent MRI in the same time intervals without contrast application (control group). Signal intensities of thalamus, pallidum, pons, dentate nucleus, and globus pallidus-to-thalamus and dentate nucleus-to-pons ratios, were determined. Gadodiamide complex and total gadolinium amount were quantified after the last MR examination via LC-MS/MS and ICP-MS. Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios showed no significant increase over time within all mice groups receiving gadodiamide, as well as compared to the control groups at last MR examination. Comparing healthy mice with group B and C after repetitive contrast administration, a significant SI increase could only be detected for glioblastoma mice in globus pallidus-to-thalamus ratio (p = 0.033), infarction mice showed no significant SI alteration. Tissue analysis revealed significantly higher gadolinium levels in glioblastoma group compared to healthy (p = 0.013) and infarction mice (p = 0.029). Multiple application of the linear contrast agent gadodiamide leads to cerebral gadolinium deposition without imaging correlate in MRI.

Long-term outcome of incidental cystic liver tumors in the general population.

Aim of this study was to investigate frequency, incidence and risk factors of liver cysts in the general population in a longitudinal survey. Cyst frequency was investigated in 607 adult volunteers (288 women, 319 men, mean age 55 years) using strong T2-weighted magnetic resonance imaging. Risk factors were investigated for occurrence, frequency and size of cystic lesions at baseline. Incidence and physiological growing of the lesions were observed in a 5-years follow-up. At baseline, 431 volunteers had 1,479 cysts (71.0%). The mean number of cysts per person was 3.4 ± 9.0. The mean size of cysts was 13.1 ± 11.7 mm. Women had a higher number of cysts than men (p = 0.026). Older and male volunteers demonstrated a higher cyst frequency (p = 0.002 and p = 0.025). Per one-year increase in age the chance for a liver cyst increased by 2%. Four-hundred seventeen volunteers had cysts in the follow-up, in 24.6% new lesions had occurred. Lesion size significantly increased in follow-up (p < 0.001). Age and male sex were associated with the occurrence of at least one liver cyst. Women had a higher average number of cysts. Cystic lesion progression is a physiological phenomenon in the long-term follow-up.

Whole-body R2∗ mapping to quantify tissue iron in iron storage organs: reference values and a genotype.

AIM: To define reference values for the transverse relaxation rate (R2∗) in iron storage organs and to investigate the role of human haemochromatosis protein (HFE) genotype on iron storage. MATERIALS AND METHODS: Whole-body magnetic resonance imaging (MRI) including a five-echo gradient-echo sequence was performed in 483 volunteers (269 men, mean age 59.3 ± 12.2 years) without clinical evidence of an iron storage disease at 1.5 T. R2∗ values were assessed for liver, spleen, pancreas, heart, bones, and brain parenchyma. The HFE genotype was determined regarding the single nucleotide polymorphisms (SNPs) rs74315324, rs1799945, rs41303501, rs1800562, rs1800730. R2∗ values were compared among participants without and with at least one mutation. R2∗ reference values were defined using volunteers without any mutation. RESULTS: Three hundred and one participants had no mutations in any HFE SNP, 182 had at least one mutation. HFE gene mutations were distributed as (heterozygous/homozygous) rs1799945:132/9, rs1800562:33/1, and rs1800730:11/0. Mean R2∗ values ± SD (per second) in the group without mutation were: liver: 33.4 ± 12.7, spleen: 24.1 ± 13.8, pancreas: 27.2 ± 6.6, heart: 32.7 ± 11.8, bone: 69.3 ± 21.0, brain parenchyma: 13.9 ± 1.2. No significant difference in R2∗ values were found between participants with and without the HFE gene mutation for any examined iron storage organ (pliver=0.09, pspleen=0.36, ppancreas = 0.08, pheart = 0.36, pbone = 0.98, pbrain=0.74). CONCLUSION: Reference values of R2∗ in iron storage organs are feasible to support the diagnosis of iron storage diseases. Non-specific mutations in HFE SNPs appear not to affect the phenotype of tissue iron accumulation.

Reduction of respiratory motion artifacts in gadoxetate-enhanced MR with a deep learning-based filter using convolutional neural network.

OBJECTIVES: To reveal the utility of motion artifact reduction with convolutional neural network (MARC) in gadoxetate disodium-enhanced multi-arterial phase MRI of the liver. METHODS: This retrospective study included 192 patients (131 men, 68.7 ± 10.3 years) receiving gadoxetate disodium-enhanced liver MRI in 2017. Datasets were submitted to a newly developed filter (MARC), consisting of 7 convolutional layers, and trained on 14,190 cropped images generated from abdominal MR images. Motion artifact for training was simulated by adding periodic k-space domain noise to the images. Original and filtered images of pre-contrast and 6 arterial phases (7 image sets per patient resulting in 1344 sets in total) were evaluated regarding motion artifacts on a 4-point scale. Lesion conspicuity in original and filtered images was ranked by side-by-side comparison. RESULTS: Of the 1344 original image sets, motion artifact score was 2 in 597, 3 in 165, and 4 in 54 sets. MARC significantly improved image quality over all phases showing an average motion artifact score of 1.97 ± 0.72 compared to 2.53 ± 0.71 in original MR images (p < 0.001). MARC improved motion scores from 2 to 1 in 177/596 (29.65%), from 3 to 2 in 119/165 (72.12%), and from 4 to 3 in 34/54 sets (62.96%). Lesion conspicuity was significantly improved (p < 0.001) without removing anatomical details. CONCLUSIONS: Motion artifacts and lesion conspicuity of gadoxetate disodium-enhanced arterial phase liver MRI were significantly improved by the MARC filter, especially in cases with substantial artifacts. This method can be of high clinical value in subjects with failing breath-hold in the scan. KEY POINTS: • This study presents a newly developed deep learning-based filter for artifact reduction using convolutional neural network (motion artifact reduction with convolutional neural network, MARC). • MARC significantly improved MR image quality after gadoxetate disodium administration by reducing motion artifacts, especially in cases with severely degraded images. • Postprocessing with MARC led to better lesion conspicuity without removing anatomical details.

Comparison of sequential and high-pitch-spiral coronary CT-angiography: image quality and radiation exposure.

New protocols for coronary computed tomography angiography (CCTA) could lower the radiation dose for patients but influence the image quality. To compare image quality and radiation exposure in step-and-shoot CCTA and high-pitch spiral CCTA. Fifty-nine pairs of patients matched for weight, height, sex and heart rate were included in this study (74 m, 44 f, average age 60 years, age range 29-94 years). Step-and-shoot CCTA and high-pitch spiral CCTA was performed on a third generation dual-source CT in equally sized patient groups. The signal-to-noise ratio (SNR) in the ascending aorta and the coronary arteries were determined for each dataset. Image quality was rated using a five-point scale. We used the t-test for paired samples to compare SNR and effective dose, and the Wilcoxon test to compare image quality scores. Mean effective dose for the step-and-shoot protocol (4.15 ± 3.07 mSv) was significantly higher in comparison to the high-pitch spiral protocol (1.2 ± 0.69 mSv; p < 0.0001). Mean SNR was higher with the step-and-shoot protocol compared to the high-pitch spiral protocol in the aorta, in the left main and peripheral coronary arteries (p < 0.01), in the proximal right coronary artery (p = 0.027). Image quality scores were significantly better for the step-and-shoot protocol (p = 0.0003). Step-and-shoot CCTA has significantly better SNR and overall image quality compared to high-pitch spiral CCTA, but with a mean effective dose more than thrice as high.

[Percutaneous biliary and gallbladder interventions]. / Perkutane Intervention der Gallenwege und der Gallenblase.

CLINICAL ISSUE: Percutaneous transhepatic biliary and gall bladder interventions play an important role in the diagnosis and therapy of biliary tract diseases. PERFORMANCE: With technical success rates up to 99% as well as complications rates up to a maximum of 26% they showed good results. Indications were opacification of the biliary tree as well as treatment of biliary system pathologies, such as drainage and stents. ACHIEVEMENTS: Interventions were used if endoscopic approaches are not possible or exploited. We describe the current state of knowledge and the range for percutaneous biliary/gall bladder interventions and give an overview of technical approaches for fundamental interventional procedures, including percutaneous transhepatic biliary drainage. PRACTICAL RECOMMENDATIONS: Percutaneous transhepatic biliary and gall bladder interventions are safe and effective treatments for benign and malignant stenosis, postoperative complications and risk patients with cholecystitis.

Abdominal fat deposits determined by magnetic resonance imaging in relation to leptin and vaspin levels as well as insulin resistance in the general adult population.

BACKGROUND: Various fat depots including visceral (VAT), subcutaneous adipose tissue (SAT) or liver fat content (LFC) were supposed to have different influences on various entities including adipokine levels as well as insulin resistance/sensitivity. Therefore, the aim of the study was to investigate the associations of SAT, VAT and LFC with the levels of leptin and vaspin as well as insulin resistance in a general non-diabetic population. METHODS: In total, 1825 participants of the Study of Health in Pomerania were characterized according to body fat compartments and LFC determined by magnetic resonance imaging. Of those subjects, insulin resistance (HOMA-IR) and insulin sensitivity ([ISI(comp)) were determined in 981 participants and adipokines were assessed in 698 using enzyme-linked immunosorbent assay. Analyses of variance and linear regression models adjusted for age, sex, smoking, height, physical inactivity and alcohol consumption were used for analysis. RESULTS: Using the residual method to assess independently the effect of the various fat depots, a strong positive association of SAT (beta per standard deviation (s.d.) increase 0.54 (95% confidence interval (CI) 0.47-0.60)) but not VAT (beta 0.01 (95% CI -0.08 to 0.09)) and LFC (beta 0.01 (95% CI -0.06 to 0.08)) with log2-leptin levels was found independent of the HOMA-IR status. Moreover, a positive association of LFC (beta 0.17 (95% CI 0.07-0.26)) with log2-vaspin levels becomes apparent, which were mostly driven by subjects with a low HOMA-IR. With respect to HOMA-IR and ISI(comp) index, pronounced positive and inverse associations to all fat markers were revealed, respectively, with the strongest relation found for SAT and LFC. CONCLUSIONS: SAT and LFC were identified as predominant sites associated with leptin and vaspin levels, respectively. Residual analysis pointed towards a general adverse effect of disproportional triglyceride storage across physiological despots, in particular in ectopic sides such as the liver, with markers of insulin resistance.

A simplified method to estimate Diphyllobothrium spp. infection in salmonids.

Some fish parasites constitute severe management problems as they may cause mortality of their fish host or are important zoonoses of humans. Parasite assessments are therefore critical to keep track of infections. If conventional sampling techniques can be simplified, parasite assessments might be easier to obtain, less time-consuming and more extensive. In this study, we compare the assessed number of Diphyllobothrium spp. cysts (CYST) with the counted number of Diphyllobothrium spp. plerocercoid larvae recovered using a conventional digestive technique (LARV). The aim was to determine the potential of using CYST as a simplified methodology for assessing Diphyllobothrium spp. infection in salmonids. In total, 365 brown trout and 424 Arctic charr were sampled from nine lakes in subarctic Norway. Strong correlation, significant linear relationship and large amount of explained variation were found between log10 CYST and log10 LARV in both fish species. The method had a slight, but not significant tendency to work better in charr compared to trout. In addition, absolute difference between CYST and LARV increased at parasite intensities >100 indicating that the method has reduced functionality when estimating parasite intensity in heavily infected salmonid populations. However, overall, using this simplified and less time-consuming methodology, a good indication of Diphyllobothrium spp. intensity, abundance and prevalence was obtained. We suggest that this method provides a sound proxy of the Diphyllobothrium spp. burden and have the potential to be used in parasite assessment during fish monitoring and fisheries management surveys, particularly if the time and resources for detailed parasite studies are not available.

[Calculating Ratios Based on Statutory Health Care Data at the District Level - An Empirical Estimation Based on the Microcensus]. / Ratenbildung bei KV-Daten mit GKV-Versicherten auf Kreisebene ­ ein empirisches Schätzmodell auf der Basis des Mikrozensus.

Background: In Germany, data of the statutory health insurance system are used, amongst others, in health monitoring and health care research at the district level. For the calculation of exact ratios, the number of those covered by statutory health insurance is needed as denominator. For some federal states, however, this number is not available on a district level. Therefore, ratios based on statutory health care data are calculated using a surrogate defined in terms of visits to the doctor. This leads to uncertainties that limit small area comparisons. Therefore, the aim of the present study was to develop a superior estimation model for the number of those covered by statutory health insurance on a district level. Methods: The proportion of those covered by statutory health insurance in the Bavarian districts is estimated by a multiple linear regression model. The model relates data on determinants of the insurance status (income, proportions of civil servants and of self-employed persons) available on district level to data on the number of those covered by statutory health insurance obtained from microcensus on a regional level. The proportion of those covered by statutory health insurance estimated by this model is compared to the surrogate. As an example for practical application, small area estimations for diabetes prevalence are compared to data provided by the Bavarian Association of Statutory Health Insurance Physicians. Results: The proportion of those covered by the statutory health insurance in the Bavarian districts as estimated by the regression model varies between 74.7 and 91.6%. The difference to the currently used surrogate reaches up to 18.6 percentage points. This is also reflected in treatment prevalence, shown here using the example of diabetes mellitus. Conclusion: The present analysis shows the uncertainties of ratios and consequences for small area comparisons based on statutory healthcare data. Providing valid data for the denominator in accordance with the data transparency regulation in the Social Insurance Code (SGB) V should be attempted.

[Clinical Phenomenology of Autoimmune Encephalitis]. / Klinische Phänomenologie der Autoimmunenzephalitiden.

Antibody-associated disorders of the central nervous system constitute a heterogeneous group of disorders that can be roughly divided into two categories: Classic paraneoplastic syndromes associated with so-called well-characterized antibodies (paraneoplastic neurological disorders, PND) and autoimmune disorders with antibodies to membrane-bound or synaptic antigens (autoimmune encephalitis, AE). The discovery of autoimmune encephalitis has led to a paradigm shift in diagnosis and therapy as well as a reclassification of some neuropsychiatric syndromes that were previously classified as idiopathic or simply covered with descriptive terms.In this review article, especially clinical aspects of autoimmune encephalitis will be discussed, as there has been a rapid increase in knowledge in this regard within the past decade; increasingly overlap syndromes and associations with other disease entities have been detected. In addition to general aspects, characteristics of anti-NMDAR-, anti-LGI1-, anti-GABAA and GABABR, anti-AMPAR-, anti-CASPR2-, anti-mGluR, anti-GlycinR-, anti-GAD, anti- DPPX- and anti-D2 R encephalitis and the anti-IgLON5 encephalopathy will be presented.

Unraveling the intrafamilial correlations and heritability of tumor types in MEN1: a Groupe d'étude des Tumeurs Endocrines study.

BACKGROUND: MEN1, which is secondary to the mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Most studies demonstrated the absence of direct genotype-phenotype correlations. The existence of a higher risk of death in the Groupe d'étude des Tumeurs Endocrines-cohort associated with a mutation in the JunD interacting domain suggests heterogeneity across families in disease expressivity. This study aims to assess the existence of modifying genetic factors by estimating the intrafamilial correlations and heritability of the six main tumor types in MEN1. METHODS: The study included 797 patients from 265 kindred and studied seven phenotypic criteria: parathyroid and pancreatic neuroendocrine tumors (NETs) and pituitary, adrenal, bronchial, and thymic (thNET) tumors and the presence of metastasis. Intrafamilial correlations and heritability estimates were calculated from family tree data using specific validated statistical analysis software. RESULTS: Intrafamilial correlations were significant and decreased along parental degrees distance for pituitary, adrenal and thNETs. The heritability of these three tumor types was consistently strong and significant with 64% (s.e.m.=0.13; P<0.001) for pituitary tumor, 65% (s.e.m.=0.21; P<0.001) for adrenal tumors, and 97% (s.e.m.=0.41; P=0.006) for thNETs. CONCLUSION: The present study shows the existence of modifying genetic factors for thymus, adrenal, and pituitary MEN1 tumor types. The identification of at-risk subgroups of individuals within cohorts is the first step toward personalization of care. Next generation sequencing on this subset of tumors will help identify the molecular basis of MEN1 variable genetic expressivity.

MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d'étude des Tumeurs Endocrines.

CONTEXT: Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only described by case reports. OBJECTIVE: To improve the knowledge of MEN1 natural history before 21 years old. METHODS: Obtain a description of the first symptoms occurring before 21 years old (clinical symptoms, biological or imaging abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs) occurring in a group of 160 patients extracted from the "Groupe d'étude des Tumeurs Endocrines" MEN1 cohort. RESULTS: The first symptoms were related to hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%), nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%), and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22 cases (14%) and before 5 years old in five cases (3%). Surgery was performed before age 21 in 66 patients (41%) with a total of 74 operations: pituitary adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%), NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET. One patient died before age 21 due to a thymic-NET. Overall, lesions were malignant in four cases. CONCLUSIONS: Various MEN1 lesions occurred frequently before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors may develop at any age. Hyperparathyroidism was the most frequently encountered lesion but was not always the first biological or clinical abnormality to appear during the course of MEN1.

Subjectively perceived personality and mood changes associated with subthalamic stimulation in patients with Parkinson's disease.

BACKGROUND: Clinical and ethical implications of personality and mood changes in Parkinson's disease (PD) patients treated with subthalamic deep brain stimulation (STN-DBS) are under debate. Although subjectively perceived personality changes are often mentioned by patients and caregivers, few empirical studies concerning these changes exist. Therefore, we analysed subjectively perceived personality and mood changes in STN-DBS PD patients. METHOD: In this prospective study of the ELSA-DBS group, 27 PD patients were assessed preoperatively and 1 year after STN-DBS surgery. Two categories, personality and mood changes, were analysed with semi-structured interviews. Patients were grouped into personality change yes/no, as well as positive/negative mood change groups. Caregivers were additionally interviewed about patients' personality changes. Characteristics of each group were assessed with standard neurological and psychiatric measurements. Predictors for changes were analysed. RESULTS: Personality changes were perceived by six of 27 (22%) patients and by 10 of 23 caregivers (44%). The preoperative hypomania trait was a significant predictor for personality change perceived by patients. Of 21 patients, 12 (57%) perceived mood as positively changed. Higher apathy and anxiety ratings were found in the negative change group. CONCLUSIONS: Our results show that a high proportion of PD patients and caregivers perceived personality changes under STN-DBS, emphasizing the relevance of this topic. Mood changed in positive and negative directions. Standard measurement scales failed to adequately reflect personality or mood changes subjectively perceived by patients. A more individualized preoperative screening and preparation for patients and caregivers, as well as postoperative support, could therefore be useful.

Association between circulating 25-hydroxyvitamin D levels and medication use in patients scheduled for cardiac surgery.

BACKGROUND AND AIM: Low vitamin D status, i.e. circulating 25-hydroxyvitamin D (25OHD) levels <50 nmol/l, is independently associated with increased CVD risk. Medication use may influence 25OHD levels. We therefore investigated the association of circulating 25OHD with medication use in patients scheduled for cardiac surgery. METHODS AND RESULTS: A total of 11,256 patients were included in this cross-sectional study. We compared 25OHD levels of medication users (18 groups of continuously used and 5 groups of intermittently used medications) with levels of non-users. Moreover, we assessed variables (medications, demographic and clinical parameters) that were independently associated with 25OHD levels <50 nmol/l. The prevalence of 25OHD levels <50 nmol/l was 65.7%. The use of statins and immunosuppressive agents was significantly associated with higher 25OHD levels and lower odds ratios of 25OHD levels <50 nmol/l. The use of ACE-inhibitors, catecholamines and antibiotics was associated with lower 25OHD levels and higher odds ratios of 25OHD levels <50 nmol/l. However, only use of antibiotics, immunosuppressive agents and catecholamines showed clinically relevant differences in 25OHD levels, i.e. differences of more than +4 nmol/l or -4 nmol/l, compared with respective non-users. These medications were prescribed either intermittently (antibiotics, catecholamines) and/or infrequently (<2%; immunosuppressive agents, catecholamines) and/or its causal relationship with circulating 25OHD is questionable (antibiotics). Female sex and blood drawing during wintertime were associated with the highest odds ratios of 25OHD levels <50 nmol/l. CONCLUSION: Data indicate that in patients with high cardiovascular risk profile medication use does not substantially contribute to 25OHD levels <50 nmol/l.

Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer's dementia.

Cholinergic neurons of the medial forebrain are considered important contributors to brain plasticity and neuromodulation. A reduction of cholinergic innervation can lead to pathophysiological changes of neurotransmission and is observed in Alzheimer's disease. Here we report on six patients with mild to moderate Alzheimer's disease (AD) treated with bilateral low-frequency deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM). During a four-week double-blind sham-controlled phase and a subsequent 11-month follow-up open label period, clinical outcome was assessed by neuropsychological examination using the Alzheimer's Disease Assessment Scale-cognitive subscale as the primary outcome measure. Electroencephalography and [(18)F]-fluoro-desoxyglucose positron emission tomography were, besides others, secondary endpoints. On the basis of stable or improved primary outcome parameters twelve months after surgery, four of the six patients were considered responders. No severe or non-transitional side effects related to the stimulation were observed. Taking into account all limitations of a pilot study, we conclude that DBS of the NBM is both technically feasible and well tolerated.

The PRIMARA study: a prospective, descriptive, observational study to review cinacalcet use in patients with primary hyperparathyroidism in clinical practice.

OBJECTIVE: Medical management of primary hyperparathyroidism (PHPT) is important in patients for whom surgery is inappropriate. We aimed to describe clinical profiles of adults with PHPT receiving cinacalcet. DESIGN: A descriptive, prospective, observational study in hospital and specialist care centres. METHODS: For patients with PHPT, aged 23-92 years, starting cinacalcet treatment for the first time, information was collected on dosing pattern, biochemistry and adverse drug reactions (ADRs). Initial cinacalcet dosage and subsequent dose changes were at the investigator's discretion. RESULTS: Of 303 evaluable patients with PHPT, 134 (44%) had symptoms at diagnosis (mostly bone pain (58) or renal stones (50)). Mean albumin-corrected serum calcium (ACSC) at baseline was 11.4 mg/dl (2.9 mmol/l). The reasons for prescribing cinacalcet included: surgery deemed inappropriate (35%), patient declined surgery (28%) and surgery failed or contraindicated (22%). Mean cinacalcet dose was 43.9 mg/day (s.d., 15.8) at treatment start and 51.3 mg/day (31.8) at month 12; 219 (72%) patients completed 12 months treatment. The main reason for cinacalcet discontinuation was parathyroidectomy (40; 13%). At 3, 6 and 12 months from the start of treatment, 63, 69 and 71% of patients, respectively, had an ACSC of ≤10.3 mg/dl vs 9.9% at baseline. Reductions from baseline in ACSC of ≥1 mg/dl were seen in 56, 63 and 60% of patients respectively. ADRs were reported in 81 patients (27%), most commonly nausea. A total of 7.6% of patients discontinued cinacalcet due to ADRs. CONCLUSIONS: Reductions in calcium levels of ≥1 mg/dl was observed in 60% of patients 12 months after initiation of cinacalcet, without notable safety concerns.

BRAF mutation in papillary thyroid carcinoma: predictive value for long-term prognosis and radioiodine sensitivity.

OBJECTIVES: BRAF pV600E mutation is the most common oncogenic event and the most specific mutation for papillary thyroid carcinoma (PTC). Many studies over the last decade have shown a direct relationship between BRAF mutation and aggressive tumour characteristics, resulting in poor prognosis. However, several recent studies have suggested that BRAF mutation is not associated with poor prognosis of PTC. The present study was designed to evaluate the association between BRAF mutation with clinicopathological factors and tumour recurrence. MATERIAL AND METHODS: In this retrospective study, BRAF mutation status was examined by direct sequencing on paraffin-embedded tumour specimens from 46 patients undergoing surgery for PTC in our institution from 1985 to 2000. The relationship between BRAF mutation and gender, advanced age, extrathyroid extension, multifocal tumour, cervical lymph node metastasis, tumour size and advanced pT stage of PTC and its predictive role for the risk of tumour recurrence were investigated with a median follow-up of 10.1 (±6.5)years. RESULTS: BRAF mutation was detected in 20 of the 46 patients (43.5%) included in the study. No statistically significant correlation was demonstrated between the presence of BRAF mutation and the various clinicopathological factors studied. No significant difference in tumour recurrence rate or radioiodine sensitivity was observed between the two subgroups: mutant BRAF and wild-type BRAF. CONCLUSION: Although BRAF mutation appears to play a role in local tumour progression, it is not a risk factor for poor prognosis or tumour recurrence in PTC.

[Interventional treatment of the acute and subacute vena cava superior syndrome]. / Interventionelle Behandlung des akuten und subakuten Vena-cava-superior-Syndroms.

BACKGROUND: Superior vena cava syndrome is defined as the lack of central venous inflow through the superior vena cava and can present a life-threatening situation. The acute situation is characterized by dyspnea and requires a fast and effective treatment. METHODS: Using two case reports, endovascular stent therapy for the treatment of acute and subacute superior vena cava syndrome is explained and discussed. RESULTS: In the first case, we introduce a patient with acute dyspnea due to decompensation of a chronic thrombosis of the superior vena cava. The second case displayed the same acute symptoms consisting of acute dyspnea and upper venous congestion due to a tumor-related compression of the superior vena cava. In both cases, the acute situation of superior vena cava syndrome was successfully treated by stent implantation. CONCLUSION: Endovascular treatment of superior vena cava syndrome is an effective option with a high technical success rate.