Commissioning of the novel Continuous Angle Multi-energy Analysis spectrometer at the Paul Scherrer Institut.

We report on the commissioning results of the cold neutron multiplexing secondary spectrometer CAMEA (Continuous Angle Multi-Energy Analysis) at the Swiss Spallation Neutron Source at the Paul Scherrer Institut, Switzerland. CAMEA is optimized for efficient data acquisition of scattered neutrons in the horizontal scattering plane, allowing for detailed and rapid mapping of low-energy excitations under extreme sample environment conditions.

Thyroid Related Quality of Life in Elderly with Subclinical Hypothyroidism and Improvement on Levothyroxine is Distinct from that in Young Patients (TSAGE).

The aim of this study was to investigate in a longitudinal approach whether levothyroxine (LT4) substitution has a different impact on quality of life (QoL) and thyroid related QoL in younger (<40 years) and older subjects (>60 years) with elevated thyroid-stimulating hormone (TSH) concentrations. The study included male and female patients with newly diagnosed, untreated subclinical hypothyroidism defined by TSH>8 mU/l. Patients were recruited throughout Germany from 2013-2016 and evaluated by clinical assessment, blood sampling and questionnaires for health related QoL and thyroid-disease thyroid-related QoL (ThyPRO) at time of diagnosis and six months after initiation of LT4 treatment. We found significantly lower QoL in both young and old patients with subclinical hypothyroidism compared to age-matched healthy individuals. Higher scores on follow-up were found in all patients irrespective of age, indicating better QoL on LT4 therapy. Analysis of the ThyPRO questionnaire showed that old patients experienced less Emotional Susceptibility, Tiredness, and Impaired Day Life on LT4, while young patients reported less Cognitive Complaints, Emotional Susceptibility, and Impaired Day Life compared to baseline assessment. Hypothyroidism with TSH concentrations>8 mU/l is associated with impairment in general and ThyPRO QoL in young and old age. Older patients benefited from LT4 therapy and remarkably show similar degree of improvement as younger patients, albeit with some thematic variation in ThyPRO QoL. Our data confirm current recommendations on initiation of LT4 substitution and suggest that this should not be withheld in elderly with TSH concentration above 8-10 mU/l.

Papillary Thyroid Cancer and Coexisting Autoimmune Thyroiditis.

Histological findings often display an association between papillary thyroid carcinomas (PTC) and autoimmune thyroiditis (AIT) and so differ significantly from follicular thyroid carcinomas (FTC). The aim of this interdisciplinary, retrospective study was to evaluate the association of AIT in patients with PTC and FTC and a control group of benign nodular goiters. One hundred thyroidectomies with histologically confirmed differentiated thyroid carcinomas, 67 with PTC and 33 with FTC, were submitted for examination. The two control groups consisted of 60 patients with euthyroid nodular goiter, displaying no signs for malignancy (no surgery) and 100 patients (second control group) with surgery of a benign nodular goiter. Controls were collected to obtain data about the incidence of significantly increased TPOAbs in the first group and of lymphocytic infiltrates (LI) in the second group. High TPOAbs were found in 35% (23/67) of patients with PTC. LI were detected by histology in 48% (32/67) of PTC. Ten patients (10/32) of this group showed the clinical and histological manifestation of a classic AIT with diffuse dense LI as well as diffuse hypoechogeneity in ultrasonography. In 7/32 cases, the histological report described focal dense LI (fAIT) and in 15/32 cases scant scattered LI. AIT and fAIT, together 25% of all PTC (17/67), showed germinal centers and can therefore be characterized as chronic autoimmune thyroiditis. In this group, high TPOAb could be detected in 94% (16/17). Scan scattered LI without germinal centers (15/32) do not represent a fAIT, although TPOAb are high in 47% (7/15). The younger age group (<45 years) showed significantly more often high TPOAbs (p<0.023) in comparison with the age-group older than 60 years. In contrast to PTC, only 4/33 (12%) patients with FTC had high TPOAb levels. We conclude that in contrast to benign euthyroid goiters and to FTC, different degrees of LI are often associated with high TPOAb levels and seem to be significantly increased in PTC, particularly prominent in younger age. There is a high coincidence between LI and high TPOAb levels. In the presence of hypoechoic thyroid nodule, signs of thyroid autoimmunity such as the presence of high TPOAbs, lymphocytic infiltration in cytology, and/or characteristic ultrasonic features, are arguments that might favor the decision for surgery if a cytologically indeterminate thyroid nodule is found and focal autonomy is excluded by szintiscan.

Low Malignancy Rates in Fine-Needle Aspiration Cytologies in a Primary Care Setting in Germany.

BACKGROUND: Reported results for thyroid nodule fine-needle aspiration (FNA) cytology mainly originate from tertiary centers. However, thyroid nodule FNA cytology is mainly performed in primary care settings for which the distribution of FNA Bethesda categories and their respective malignancy rates are largely unknown. Therefore, this study investigated FNA cytology malignancy rates of a large primary care setting to determine to what extent current evidence-based strategies for the malignancy risk stratification of thyroid nodules are applied and applicable in such primary care settings. METHODS: In a primary care setting, 9460 FNAs of thyroid nodules were retrospectively analyzed from 8380 patients evaluated by one cytologist (I.R.) during a period of two years. The 8380 FNA cytologies were performed by 64 physicians in different private practices throughout Germany in primary care settings. RESULTS: The cytopathologic results were classified according to the Bethesda System as non-diagnostic in 19%, cyst/cystic nodule in 21%, benign (including thyroiditis) in 48%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 6%, follicular neoplasms/suspicious for follicular neoplasm (FN/SFN) in 4%, suspicious for malignancy (SFM) in 1%, and malignant in 1%. The proportion of patients proceeding to surgery or with a follow-up of at least one year and the observed risks of malignancy were 22%/8% for AUS/FLUS, 69%/17% for FN/SFN, 78%/86% for SFM, and 71%/98% for malignant. For 112 cytologically suspicious and malignant FNAs, there were 102 true positives and 10 false positives, considering histology as gold standard. CONCLUSION: At variance with other data mostly originating from tertiary centers, these data demonstrate low percentages for malignant, SFM, FN/SFN, and AUS/FLUS, and high percentages for cysts/cystic nodules in this primary care setting in Germany. The risks of malignancy for malignant, SFM, AUS/FLUS, and FN/SFN FNA cytologies are according to Bethesda recommendations.

Evaluation of a Two-Year Routine Application of Molecular Testing of Thyroid Fine-Needle Aspirations Using a Seven-Gene Panel in a Primary Referral Setting in Germany.

BACKGROUND: Major differences with respect to the diagnostic performance of a "ruling in" approach in the presurgical diagnosis of indeterminate thyroid fine-needle aspirations (FNAs) have been reported. Therefore, the aim of this prospective multicenter study was to investigate the specific diagnostic impact of mutation testing using a seven-gene panel in a routine primary referral setting analyzing FNAs from endocrinology and nuclear medicine practices in Germany. METHODS: RNA and DNA was extracted from 564 routine air-dried FNA smears obtained from 64 physicians and cytologically graded by one experienced cytopathologist. PAX8/PPARG and RET/PTC rearrangements were detected by quantitative polymerase chain reaction, while BRAF and RAS mutations were detected by pyrosequencing. Molecular data were compared to histology and follow-up >1 year, which were available for 322/348 patients undergoing surgery and 33/74 patients having follow-up. Histology results were obtained from the local routine pathologists who were blinded to the molecular test results. RESULTS: BRAF and RET/PTC mutations were associated with carcinoma in 98% and 100% of samples, respectively. RAS and PAX8/PPARG mutations were associated with carcinoma in 31% and 0% of samples, respectively. Thirty-six percent of the carcinomas were identified by molecular testing in the atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for a follicular neoplasm categories, with malignancy rates of 15% and 17%, respectively. Due to a low percentage of RAS mutation-positive carcinomas in combination with a rather high percentage of RAS mutation-positive benign nodules, the positive predictive values of 41% and 36% in the atypia of undetermined significance/follicular lesion of undetermined significance and follicular neoplasm/suspicious for a follicular neoplasm categories offer only limited diagnostic potential. CONCLUSION: In conclusion, the data suggest that the application of the current seven-gene panel in a routine primary referral setting does not improve the presurgical diagnosis of thyroid FNAs. While the diagnostic relevance of RAS mutations in thyroid tumors needs further investigation, more comprehensive mutation panels with more cancer-specific mutations may improve the presurgical diagnosis of thyroid FNAs.

[Osteoporosis]. / Osteoporose.

Osteoporosis is among the main causes for bone fractures. In this overview we report on the prevalence of the disease, the diagnostic procedures, and the therapeutic options. The prevalence increases with age and women are more often affected than men. The diagnosis usually is made on the basis of dual X-ray absorptiometry. Prophylactic measures include a sufficient intake of calcium and vitamin D. Bisphosphonates play a central role in the pharmacotherapy of this disease.

CAMEA--A novel multiplexing analyzer for neutron spectroscopy.

The analyzer detector system continuous angle multiple energy analysis will be installed on the cold-neutron triple-axis spectrometer RITA-2 at SINQ, PSI. CAMEA is optimized for efficiency in the horizontal scattering plane enabling rapid and detailed mapping of excitations. As a novelty the design employs a series of several sequential upward scattering analyzer arcs. Each arc is set to a different, fixed, final energy and scatters neutrons towards position sensitive detectors. Thus, neutrons with different final energies are recorded simultaneously over a large angular range. In a single data-acquisition many entire constant-energy lines in the horizontal scattering plane are recorded for a quasi-continuous angular coverage of about 60°. With a large combined coverage in energy and momentum, this will result in a very efficient spectrometer, which will be particularly suited for parametric studies under extreme conditions with restrictive sample environments (high field magnets or pressure cells) and for small samples of novel materials. In this paper we outline the concept and the specifications of the instrument currently under construction.