[Thyroid nodules: The Guidelines of the American Thyroid Association from a European Perspective]. / Schilddrüsenknoten: ATA-Leitlinie aus europäischer Sicht.

In Germany and in other regions with former iodine deficiency, thyroid nodules and nodular goiter are still much more frequent than in the U.S.A. The American Thyroid Association (ATA) has published 2015 revised guidelines for patients with thyroid nodules and differentiated thyroid cancer. For evaluation of suspected thyroid nodules the authors describe high, intermediate, low and very low suspicion pattern and recommend further fine needle aspiration cytology, depending on the pattern and the size of the nodule. The high suspicion pattern includes irregular margins of the nodule, which may be an important criterion for malignancy of solitary nodules. In nodular goiters with multiple nodules grown together and without clear margins, frequently observed in former iodine deficiency regions, irregular margins may not be a significant criterion for malignancy. Another pattern, hypoechogenicity, which is frequently seen in benign nodules in former iodine deficiency areas, is also not a clear criterion for malignancy. Only strong hypoechogenicity may indicate malignancy. Another difference relates to the recommendation of scintigraphy that according to the guideline is restricted to patients with decreased TSH. In regions with former iodine deficiency, it has been demonstrated that thyroid autonomy may be present even if TSH is in the lower normal range. Therefore, in Germany scintigraphy is recommended for preoperative evaluation of all patients with thyroid nodules or nodular goiter.

[Medical Treatment of Thyroid Nodule]. / Medikamentöse Therapie des Schilddrüsenknotens.

Whereas in regions with sufficient iodide intake treatment of thyroid nodules with levothyroxine has been almost completely abandoned and is also not further recommended by guidelines, medical treatment may be still indicated in Germany as recently demonstrated by randomized, placebo-controlled LISA study.A major reason for this is mild iodide deficiency in patients with thyroid nodules. In LISA study a combined therapy of levothyroxine and iodide resulted in an at least 50 % reduction of nodular volume in 21,6 % of treated patient compared to in only 5,2 % of placebo-treated patients.To avoid TSH suppression levothyroxine dose must be adjusted that TSH is in the lower reference range, since subclinical hyperthyroidism may result in cardiac adverse events as arrythmias.In the elderly the cardiac risk has to be considered and levothyroxine dose has frequently to be reduced or therapy even to be stopped.

Anti-Insulin Antibodies and Adverse Events with Biosimilar Insulin Lispro Compared with Humalog Insulin Lispro in People with Diabetes.

BACKGROUND: SAR342434 (SAR-Lis) is a biosimilar (follow-on) of insulin lispro (Humalog®; Ly-Lis). Two randomized, controlled, open-label, parallel-group, phase 3 studies were conducted to compare the efficacy and safety of SAR-Lis and Ly-Lis, both in combination with insulin glargine (Lantus®). SORELLA 1 was a 12-month study in 507 people with type 1 diabetes mellitus (T1DM); SORELLA 2 was a 6-month study in 505 people with type 2 diabetes mellitus (T2DM). In this study, the impact of anti-insulin antibodies (AIA) to SAR-Lis and Ly-Lis on safety and glycemic control is reported. METHODS: AIA were measured regularly throughout both studies at a centralized laboratory blinded to treatment groups using a drug-specific AIA assay. The AIA status (positive or negative), AIA titers, and cross-reactivity to human insulin, insulin glargine, and insulin glargine metabolite M1 were analyzed. The potential effect of AIA on safety, particularly as related to hypersensitivity reactions, hypoglycemia, and treatment-emergent adverse events, as well as on glycemic control (HbA1c, insulin dose), was evaluated. RESULTS: AIA positive status at baseline was similar for the two insulins, but higher in T1DM than in T2DM. In both studies, the percentage of people newly developing AIA in the two treatment groups, or having a ≥4-fold increase in AIA titers, did not differ. No relationship was observed between maximum individual AIA titers and change in HbA1c or insulin dose, hypoglycemia, or hypersensitivity reactions or between efficacy/safety measures and subgroups by presence or absence of treatment-emergent AIA. Hypersensitivity events and events adjudicated as allergic reactions were few and did not differ between the two groups. CONCLUSION: Insulin lispro SAR342434 and the originator insulin lispro had a similar immunogenicity profile in people with T1DM or T2DM.

Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 2 Diabetes, Also Using Insulin Glargine: SORELLA 2 Study.

BACKGROUND: SAR342434 (SAR-Lis) is a biosimilar (follow-on) of insulin lispro (U100; Humalog®; Ly-Lis). This study aimed to show similar efficacy, safety, and immunogenicity of SAR-Lis versus Ly-Lis in adult patients with type 2 diabetes mellitus (T2DM) treated with multiple daily injections, while using insulin glargine (GLA-100; Lantus®) as basal insulin. METHODS: SORELLA 2 was a 6-month, randomized, open-label, Phase 3 study (NCT02294474). Insulin doses were adjusted to achieve fasting and 2-h postprandial glucose targets according to American Diabetes Association guidelines. Primary endpoint was the HbA1c change from baseline to week 26 (tested for noninferiority of SAR-Lis vs. Ly-Lis with a margin of 0.3%). Secondary endpoints included fasting plasma glucose (FPG), seven-point self-monitored plasma glucose (SMPG) profiles, hypoglycemic events, treatment-emergent adverse events (TEAEs), and anti-insulin antibodies (AIA). RESULTS: A total of 505 patients were randomized (1:1) to multiple daily injections of SAR-Lis (n = 253) or Ly-Lis (n = 252) plus once-daily GLA-100. Least square (LS) mean (standard error) change in HbA1c from baseline to week 26 was similar in both treatment groups (SAR-Lis, -0.92% [0.051] and Ly-Lis, -0.85% [0.051]). Noninferiority at prespecified 0.3% noninferiority margin was demonstrated (LS mean difference of SAR-Lis vs. Ly-Lis: -0.07% [95% CI: -0.215 to 0.067]) as was inverse noninferiority. Similar changes in FPG, seven-point SMPG profiles, including postprandial glucose excursions and mean glucose over 24 h, and insulin dosages were observed in the two groups. Hypoglycemia, TEAEs, and AIA (incidence and prevalence) did not differ between groups. CONCLUSIONS: Results from this controlled study in patients with T2DM also using GLA-100 support similar efficacy and safety (including immunogenicity) of SAR-Lis and Ly-Lis.

Comparison Between Various Color Spectra and Conventional Grayscale Imaging for Detection of Parenchymal Liver Lesions With B-Mode Sonography.

OBJECTIVES: The electronic colorization of grayscale B-mode sonograms using various color schemes aims to enhance the adaptability and practicability of B-mode sonography in daylight conditions. The purpose of this study was to determine the diagnostic effectiveness and importance of colorized B-mode sonography. METHODS: Fifty-three video sequences of sonographic examinations of the liver were digitized and subsequently colorized in 2 different color combinations (yellow-brown and blue-white). The set of 53 images consisted of 33 with isoechoic masses, 8 with obvious lesions of the liver (hypoechoic or hyperechoic), and 12 with inconspicuous reference images of the liver. The video sequences were combined in a random order and edited into half-hour video clips. RESULTS: Isoechoic liver lesions were successfully detected in 58% of the yellow-brown video sequences and in 57% of the grayscale video sequences (P = .74, not significant). Fifty percent of the isoechoic liver lesions were successfully detected in the blue-white video sequences, as opposed to a 55% detection rate in the corresponding grayscale video sequences (P= .11, not significant). In 2 subgroups, significantly more liver lesions were detected with grayscale sonography compared to blue-white sonography. CONCLUSIONS: Yellow-brown-colorized B-mode sonography appears to be similarly effective for detection of isoechoic parenchymal liver lesions as traditional grayscale sonography. Blue-white colorization in B-mode sonography is probably not as effective as grayscale sonography, although a statistically significant disadvantage was shown only in the subgroup of hyperechoic liver lesions.

In situ cooling with ice water for the easier removal of self-expanding nitinol stents.

BACKGROUND: It is yet to be determined what effects temperature has on the properties of nitinol in order to simplify the process of removing nitinol self-expanding metal stents (SEMS). MATERIALS AND METHODS: We describe the procedure for removal of SEMS in a total of 11 cases with 9 patients. A study involving cooling of nitinol stents in situ with ice water just before their removal was attempted. RESULTS: All stents were removed successfully. In partially covered and in fully covered stents, the stent rigidity was noticeably reduced following cooling. Stent removal was performed by inversion, which was achieved by pulling on the stent from its distal end. No adverse events were observed during this trial. CONCLUSION: The higher pliability of the stents after ice-water cooling facilitates stent removal. With this method, a mobilization of all stents by the invagination technique was achieved. The separation of the uncoated stent ends from the intestinal wall by the invagination technique, as well as the mucosal vasoconstriction resulting from the cooling, lead to an easier SEMS removal and may serve to prevent severe bleeding of the mucosal wall during this process.

Randomized forced titration to different doses of technosphere insulin demonstrates reduction in postprandial glucose excursions and hemoglobin A1c in patients with type 2 diabetes.

BACKGROUND: Individuals with type 2 diabetes mellitus have impairments in early insulin release, resulting in increased postprandial glucose excursions and suboptimal glycemic control. Studies with Technosphere Insulin (TI) indicate that it has rapid systemic absorption and a short duration of glucose-lowering activity, making it well suited for controlling postprandial glucose levels. METHODS: The goal of this phase 2b, prospective, multicenter, double-blind, placebo-controlled study was to characterize the dose response of four different doses (equivalent to 3.6, 7.3, 10.9, and 14.6 U subcutaneous regular human insulin) of prandial TI or Technosphere powder alone administered before each of three meals daily, in combination with insulin glargine over an 11-week treatment period, in patients with type 2 diabetes and suboptimal glycemic control. RESULTS: The study enrolled 227 patients. In all dose groups, TI demonstrated statistically significant dose-dependent reductions in hemoglobin A1c (HbA1c) versus baseline (-0.4, -0.5, -0.5, and -0.6 for 3.6, 7.3, 10.9, and 14.6 U equivalents, respectively; p < 0.05 in all groups), as well as versus placebo or Technosphere powder alone (-0.40, -0.67, -0.70, and -0.78 for 3.6, 7.3, 10.9, and 14.6 U equivalents, respectively; p < 0.04 in all groups). It reduced the postprandial maximum glucose concentration within each treatment group (statistically significant in all but the TI 3.6 U-equivalent group) and reduced the postprandial area under the glucose curve (statistically significant for the TI 10.9 and 14.6 U-equivalent groups) versus placebo. There were no cases of severe hypoglycemia, while mild/moderate hypoglycemia was observed most frequently in the highest dosage groups, as expected. Rates of cough were low and comparable among all groups. No clinically relevant changes in pulmonary function tests, body weight, or high-resolution computerized axial tomography and magnetic resonance imaging were observed. CONCLUSIONS: This study demonstrated that, over 11 weeks, TI plus basal insulin glargine is well tolerated and results in dose-dependent reductions in postprandial glucose and HbA1c levels.