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.

Antimicrobial and anti-inflammatory potential therapy for opportunistic microorganisms.

INTRODUCTION: Methanolic extracts of six plants (Arbutus andrachne, Chrysanthemum coronarium, Inula viscosa, Origanum syriacum, Punica granatum, and Rosmarinus officinalis) used in traditional medicine for the treatment of bacterial and fungal infections were evaluated. The present study was conducted to evaluate the antimicrobial and anti-inflammatory activity of some medicinal plants in lowering the risk of opportunistic infections of the oral cavity caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. Extracts were evaluated separately and in a mixture. METHODOLOGY: The methanolic plant extracts were tested against three opportunistic microorganisms by determining the minimum inhibitory concentration (MIC). They were also evaluated for their ability to suppress the release of the pro-inflammatory cytokine IL-6 while not suppressing the release of the anti-inflammatory cytokine IL-10 from peripheral blood mononuclear cells using ELISA. RESULTS: All extracts showed both antimicrobial and anti-inflammatory activities. However, O. syriacum exhibited the highest antimicrobial activity for the three microorganisms among all of the tested extracts (MIC S. aureus: 1 mg/mL; P. aeruginosa: 2 mg/mL; and C. albicans: 1 mg/mL). The extracts inhibited the expression of the pro-inflammatory cytokine IL-6 with apparent dose-dependent responses while they attenuated the secretion of the anti-inflammatory cytokine IL-10. The mixture of O. syriacum and R. officinalis showed an anti-inflammatory effect, with a synergistic antimicrobial effect. CONCLUSION: These findings support the idea that a diet rich in plants and herbs may contribute to the reduction of inflammation and microbial growth and may also be preventive against various infections, including those related to the oral cavity.

Assessment of a controlled release hydrophilic matrix formulation for metoclopramide HCl.

Metoclopramide HCl showed controlled release behavior when embedded in a hydrophilic matrix of chitosan and sodium alginate. The in vitro release data was found to be first order according to the Higuchi mechanism. An in vivo evaluation of the metoclopramide controlled release matrix on six male volunteers was carried out. The plasma samples were analyzed using a high-performance liquid chromatography (HPLC) method using a mobile phase of acetonitrile:acetic acid (30:70), with the pH adjusted to 4.7, a reverse phase Hypersil BDS Phenyl column (4 microm, 250 x 4 mm) and the detection was performed at 305 nm. The controlled release formula was found to be effective in delaying absorption (t(max) 4.5h as compared to 1.2h), reducing the peak plasma concentrations (C(max) 63.4 ng/ml as compared to 95.9 ng/ml) and maintaining higher concentrations during the elimination phase when compared to the immediate release formula. This proves the suitability of the suggested system for further studies.