Polyethylene glycol-coated collagen patch (hemopatch®) in open partial nephrectomy.

PURPOSE: To describe the results of a polyethylene glycol-coated collagen patch, Hemopatch® on blood loss, surgical time and renal function in partial nephrectomy (PN) for renal cell carcinoma (RCC). METHODS: Out of a single surgeon cohort of n = 565 patients undergoing conventional open PN (CPN) between 01/2015 and 12/2017 at the University of Munich a consecutive subgroup (n = 42) was operated on using a polyethylene glycol-coated collagen-based sealant Hemopatch® (Baxter International Inc., Deerfield, IL, USA) (HPN). RESULTS: Median age was 65.2 years (range 12.7-95.2) with median follow-up of 9.43 months (0.03-49.15). Baseline renal function (CKD-EPI) was 78.56 ml/min/1.73 m2 (range 20.38-143.09) with a non-significant decline to 74.78 ml/min/1.73 m2 (range 3.75-167.74) at follow-up. In CPN 46% had low complexity, 33% moderate complexity and 20% high complexity lesions with 33% low, 40% moderate and 27% high complexity masses in HPN. Median tumor size was 4.3 cm (range 1-38 cm) in CPN with 4.8 cm (range 3.8-18.3 cm) with HPN, p = 0.293. Median blood loss and duration of surgery was significantly lower in the HPN group vs. CPN (146 ml ± 195 vs. 114 ml ± 159 ml; p = 0.021; 43 min ± 27 for HPN vs. 53 min ± 49; p = 0.035) with no difference in clamping time (12.6 min ± 8.6 for HPN vs. 12.0 min ± 9.5; p = 0.701). CONCLUSIONS: Hemopatch® supported renoraphy shows promising results compared to standard renoraphy in PN. No side effects were seen. Further studies should evaluate the prevention of arterio-venous or urinary fistulas. In complex partial nephrectomies Hemopatch® supported renoraphy should be considered.

Red blood cell concentrates treated with the amustaline (S-303) pathogen reduction system and stored for 35 days retain post-transfusion viability: results of a two-centre study.

BACKGROUND AND OBJECTIVES: Pathogen reduction technology using amustaline (S-303) was developed to reduce the risk of transfusion-transmitted infection and adverse effects of residual leucocytes. In this study, the viability of red blood cells (RBCs) prepared with a second-generation process and stored for 35 days was evaluated in two different blood centres. MATERIALS AND METHODS: In a single-blind, randomized, controlled, two-period crossover study (n = 42 healthy subjects), amustaline-treated (Test) or Control RBCs were prepared in random sequence and stored for 35 days. On day 35, an aliquot of 51 Cr/99m Tc radiolabeled RBCs was transfused. In a subgroup of 26 evaluable subjects, 24-h RBC post-transfusion recovery, mean life span, median life span (T50 ) and life span area under the curve (AUC) were analysed. RESULTS: The mean 24-h post-transfusion recovery of Test and Control RBCs was comparable (83·2 ± 5·2 and 84·9 ± 5·9%, respectively; P = 0·06) and consistent with the US Food and Drug Administration (FDA) criteria for acceptable RBC viability. There were differences in the T50 between Test and Control RBCs (33·5 and 39·7 days, respectively; P < 0·001), however, these were within published reference ranges of 28-35 days. The AUC (per cent surviving × days) for Test and Control RBCs was similar (22·6 and 23·1 per cent surviving cells × days, respectively; P > 0·05). Following infusion of Test RBCs, there were no clinically relevant abnormal laboratory values or adverse events. CONCLUSION: RBCs prepared using amustaline pathogen reduction meet the FDA criteria for post-transfusion recovery and are metabolically and physiologically appropriate for transfusion following 35 days of storage.

[Autoimmune diseases of the thyroid gland]. / Autoimmune Schilddrüsenerkrankungen.

Autoimmune diseases of the thyroid gland are considered to be the most frequent cause of thyroid gland disorders. Autoimmune thyroid diseases consist of two subgroups: autoimmune thyroiditis (AIT) and Graves' disease. The AIT is the most common human autoimmune disease. Infiltration of the thyroid gland with cytotoxic T­cells can lead to an initial thyrotoxicosis und during the course to hypothyroidism due to destruction of the thyroid gland. Substitution with Levothyroxine is indicated for manifest hypothyroidism and subclinical hypothyroidism with increased thyroid antibodies with the intention of normalizing the serum thyroid stimulating hormone (TSH). Graves' disease is characterized by the appearance of stimulating TSH receptor antibodies leading to hyperthyroidism. Endocrine ophthalmopathy may also occur. Ablative therapy with radioiodine therapy or thyroidectomy is administered to patients with Graves' disease without remission after at least 1 year of antithyroid drug therapy.

Anti-Thyroperoxidase Antibody Levels >500 IU/ml Indicate a Moderately Increased Risk for Developing Hypothyroidism in Autoimmune Thyroiditis.

Autoimmune Thyroiditis (AIT) is the most common autoimmune disease, which is characterized by cellular and humoral immunity leading to thyroid destruction. The impact of the humoral immunity on the risk to develop hypothyroidism has not exactly been defined yet. The aim of the present study was to investigate the association between thyroid antibody levels and the risk for developing hypothyroidism. In this retrospective study, 335 untreated AIT patients were enrolled. Anti-thyroperoxidase (TPO) antibodies, anti-thyroglobulin (Tg) antibodies (Abs), and the TSH level were measured. Patients with TPO-Ab levels>500 IU/ml showed a moderately increased risk of having elevated TSH levels [p=0.0023; relative risk (95% confidence interval): 1.343 (1.108-1.627)] compared to those below this threshold. AIT patients with TPO- or Tg-Abs<100 IU/ml and between 100-500 IU/ml had no significantly different TSH levels. Presence of Tg-Abs alone or in combination with TPO-Abs did not help to increase the sensitivity to identify patients at risk. Long term follow-up of AIT patients with high TPO-Abs level (>500 IU/ml) showed an increase of TSH levels (mean: 0.5 mIU/l; range: 2.52±2.73 to 3.02±3.05 mIU/l; p=0.0420). Still, these patients remained euthyroid. Our data indicate largely elevated levels of TPO-Abs being associated with a moderately increased risk of developing hypothyroidism.

The Effect of Early Thyroidectomy on the Course of Active Graves' Orbitopathy (GO): A Retrospective Case Study.

The aim of the work was to investigate the effect of early thyroidectomy on the course of active Graves' orbitopathy (GO) in patients with low probability of remission [high TSH receptor antibody (TRAb) serum levels, severe GO] compared to that of continued therapy with antithyroid drugs. Two cohorts were evaluated retrospectively (total n=92 patients with active GO, CAS≥4). Forty-six patients underwent early thyroidectomy (Tx-group) 6±2 months after initiation of antithyroid drug (ATD) therapy, while ATD was continued for another 6±2 months in the ATD-group (n=46). These controls were consecutively chosen from a database and matched to the Tx-group. GO was evaluated (activity, severity, TRAb) at baseline and at 6 month follow-up. At baseline, both cohorts were virtually identical as to disease severity, activity and duration, as well as prior anti-inflammatory treatment, age, gender, and smoking behavior. At 6 month follow-up, NOSPECS severity score was significantly decreased within each group, but did not differ between both groups. However, significantly more patients of the Tx-group presented with inactive GO (89.1 vs. 67.4%, * p=0.02), and mean CAS score was significantly lower in Tx-group (2.1) than in ADT-group (2.8; * p=0.02) at the end of follow-up. TRAb levels declined in both groups (Tx-group: from 18.6 to 5.2 vs. ATD-group: 12.8-3.2 IU/l, p0=0.07, p6months=0.32). Residual GO activity was lower in Tx-group, associated with a higher rate of inactivation of GO. This allows an earlier initiation of ophthalmosurgical rehabilitation in patients with severe GO, which may positively influence quality of life of the patients.

Clinical Evaluation of the First Automated Assay for the Detection of Stimulating TSH Receptor Autoantibodies.

Until recently, stimulating TSH receptor autoantibodies (sTRAbs) could only be measured by bioassays. A new assay system, which directly detects sTRAb in sera by applying bridge technology, has been established and is now available as automated chemiluminescence (bridge) immunoassay. We evaluated the automated bridge assay in clinical routine and compared it with a conventional automated TRAb assay (competition assay). Altogether, 226 Graves' disease (GD), 57 autoimmune thyroiditis, 74 non-autoimmune nodular goiter and 49 thyroid cancer patients, as well as 41 healthy controls were retrospectively evaluated. ROC plot analysis based on sera of newly diagnosed GD patients revealed an area under curve of 0.99 (95% CI: 0.99-1.0) indicating a high assay sensitivity and specificity. The highest sensitivity (100%) and specificity (99%) were seen at a cut-off level of 0.55 IU/l. The calculated positive predictive value was 94%, whereas the negative was 100%. Applying a ROC plot-derived cut-off of≥0.30 IU/l, derived from sera of GD patients already receiving antithyroid drug therapy for≤6 months, the sensitivity was 99% whereas the specificity was 98%. Detailed comparison of both assay systems used revealed a slightly different distribution of sTRAb and TRAb. Measurement of sTRAb during follow-up revealed a steady decline over one year of follow-up. In summary, our results demonstrate that the new automated bridge assay system for detecting sTRAb has a high sensitivity and specificity for diagnosing GD and to discriminate from other thyroid diseases, respectively. Our study, however, does not provide full evidence that the bridge assay is specific for sTRAb only.

Quality of red cells after combination of prion reduction and treatment with the intercept system for pathogen inactivation.

BACKGROUND AND OBJECTIVES: The pathogen inactivation (PI) INTERCEPT Blood System for Red Blood Cells utilises amustaline (S-303) to inactivate a broad range of pathogens in red cell concentrates (RCC). The aim of this study was to investigate the effect on red cell quality of INTERCEPT treatment with and without prion reduction. METHODS/MATERIALS: Five pools of five RCC each were prepared. These were split and treated as follows: (i) stored at 2-6 °C for 18 h, (ii) stored at 18-24 °C for 18 h, (iii) PI-treated, (iv) PI-treated then prion reduced and (v) prion reduced then PI-treated. Prior to storage, PI-treated RCC underwent an exchange step to remove S-303 and other breakdown products. Components were tested throughout 35 days of storage for in vitro parameters of red cell quality. RESULTS: All RCC met specification for volume and haemoglobin content. Haemolysis, microvesicle formation, supernatant potassium and deformability were lower and ATP levels higher in PI-treated units when compared with control units. The effect of prion reduction in addition to PI treatment was minimal in all parameters tested except haemolysis, which was increased in units prion-reduced after being PI-treated. CONCLUSION: The PI-treatment process did not increase red cell haemolysis or decrease ATP levels over storage. The lower haemolysis and supernatant potassium levels in treated RCC compared with control RCC were attributed to the exchange step. The effects of combining PI treatment and prion reduction were not more than additive when prion reduction precedes PI treatment.

[The Choosing Wisely Initiative of the German Society of Internal Medicine : Recommendations of the German Society for Endocrinology and the German Society for Geriatrics]. / Die Klug-entscheiden-Initiative der Deutschen Gesellschaft für Innere Medizin : Empfehlungen der Deutschen Gesellschaft für Endokrinologie und der Deutschen Gesellschaft für Geriatrie.

POSITIVE RECOMMENDATIONS: A. After osteoporotic fractures in the elderly, as a rule specific antiosteoporotic therapy should be initiated. a. Osteoporosis as a disease of the elderly should be diagnosed and treated (recommendation of the German Society for Geriatrics). B. All patients with diabetes mellitus should complete a specific diabetes training program when antidiabetic drug medication is initiated. C. In Germany, all pregnant women should be advised to undertake iodine supplementation. D. Endocrine causes of hypertension should be ruled out in younger patients and in patients on multiple antihypertensive drugs. E. All unclear cases of hypercalcemia should be clarified. NEGATIVE RECOMMENDATIONS: A. Testosterone substitution therapy should not be initiated on the basis of only one measurement of a reduced testosterone level without clinical signs and clarification of the underlying cause. B. Imaging procedures should only be used after the existence of hormonal disease has been confirmed. C. Sonographic screening for thyroid disease is not advised in the elderly. D. Long-term therapy with levothyroxine for nodular goiter should be avoided. E. In relevant stress situations hydrocortisone replacement therapy should not be continued without dose adjustment in patients with adrenal or pituitary insufficiency.

[Neuroendocrine neoplasms of the breast]. / Neuroendokrine Neoplasien der Mamma.

Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.

Encapsulation status of papillary thyroid microcarcinomas is associated with the risk of lymph node metastases and tumor multifocality.

The management of papillary microcarcinoma (PMC) of the thyroid is controversial, especially after partial thyroid resection for benign thyroid disease. In order to detect prognostic factors for PMC, we analyzed 116 patients with PMC for encapsulation status and lymph node metastases. Between 10/1992 and 12/2010, 116 patients with PMC have been operated in our department (87 females, 29 males, median age 49 years). Eighty per cent of PMCs were diagnosed postoperatively. Seventy-six patients (66%) received a more extended resection with either thyroidectomy, near total thyroidectomy, or Dunhill operation either primarily or after completion operation, whereas 40 patients (34%) had only partial resection. Fifty patients (43%) received radioiodine (RIA) ablation. Lymph node metastases were found in 21 patients (18%). Univariate analysis showed four risk factors to be significantly associated with the risk of lymph node metastasis (p<0.05): male gender, younger age, age group<50 years and nonencapsulation of the tumor. Multivariate analysis demonstrated statistical significance for gender and tumor capsulation status. The tumor capsulation status also correlated with tumor multifocality. Our data show that the risk of lymph node metastases is significantly higher in partially or nonencapsulated PMC than in encapsulated specimens. We therefore suggest that the WHO classification should be extended to a compulsory notification of the encapsulation status in PMC.

[Neuroendocrine neoplasms of the distal jejunum and ileum]. / Neuroendokrine Neoplasien des distalen Jejunums und Ileums.

Neuroendocrine neoplasms (NEN) of the distal jejunum and ileum derive from serotonin-producing enterochromaffin (EC) cells. Due to their low proliferation rate and their infiltrative growth, they are often discovered at an advanced disease stage when metastasis has already occurred. The biology of these tumours is different from other NEN of the digestive tract. In order to standardise and improve diagnosis and therapy, the guidelines for the diagnosis and clinical management of jejuno-ileal NEN as well as for the management of patients with liver and other distant metastases from NEN were revised by the European Neuroendocrine Tumour Society (ENETS) in 2012. This review focuses on aspects relevant for surgical pathology.

Comprehensive genomic analysis of adrenocortical carcinoma reveals genetic profiles associated with patient survival.

BACKGROUND: Adrenocortical carcinoma (ACC) is one of the most lethal endocrine malignancies and there is a lack of clinically useful markers for prognosis and patient stratification. Therefore our aim was to identify clinical and genetic markers that predict outcome in patients with ACC. METHODS: Clinical and genetic data from a total of 162 patients with ACC were analyzed by combining an independent cohort consisting of tumors from Yale School of Medicine, Karolinska Institutet, and Düsseldorf University (YKD) with two public databases [The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)]. We used a novel bioinformatical pipeline combining differential expression and messenger RNA (mRNA)- and DNA-dependent survival. Data included reanalysis of previously conducted whole-exome sequencing (WES) for the YKD cohort, WES and RNA data for the TCGA cohort, and RNA data for the GEO cohort. RESULTS: We identified 3903 significant differentially expressed genes when comparing ACC and adrenocortical adenoma, and the mRNA expression levels of 461/3903 genes significantly impacted survival. Subsequent analysis revealed 45 of these genes to be mutated in patients with significantly worse survival. The relationship was significant even after adjusting for stage and age. Protein-protein interaction showed previously unexplored interactions among many of the 45 proteins, including the cancer-related proteins DNA polymerase delta 1 (POLD1), aurora kinase A (AURKA), and kinesin family member 23 (KIF23). Furthermore 14 of the proteins had significant interactions with TP53 which is the most frequently mutated gene in the germline of patients with ACC. CONCLUSIONS: Using a multiparameter approach, we identified 45 genes that significantly influenced survival. Notably, many of these genes have protein interactions not previously implicated in ACC. These findings may lay the foundation for improved prognostication and future targeted therapies.

MicroRNA expressions in PMBCs, CD4+, and CD8+ T-cells from patients suffering from autoimmune Addison's disease.

Autoimmune Addison's disease (AD) is a rare but potentially life threatening disease. The exact etiology of the immune response to the adrenal gland is still unknown. MicroRNAs (miRNAs) critically control gene-expression and play an important role in regulating the immune response. The aim of this study was to determine key immunoregulatory miRNAs influencing autoimmune adrenal insufficiency. For this purpose selected miRNAs were amplified by a semiquantitative SYBR Green PCR from blood mononuclear cells and after purification from CD4+ and CD 8+ cells of 6 patients with autoimmune adrenal insufficiency and 10 healthy controls. In CD4+ T-cells miRNA 181a*_1 (18.02 in AD vs. 11.99 in CG, p=0.0047) is significantly increased whereas miRNA 200a_1 (12.48 in AD vs. 19.40 in CG, p=0.0003) and miRNA 200a_2* (8.59 in AD vs. 17.94 in CG, p=0.0160) are significantly decreased. miRNA 200a_1 (12.37 in AD group vs. 18.12 in control group, p=0.001) and miRNA 200a_2* (10.72 in AD group vs. 17.84 in control group, p=0.022) are also significantly decreased in CD8+ T-cells. This study could show for the first time a significant change of three defined miRNAs in PBMCs, CD4+, and CD8+ T-cells of autoimmune AD patients in vivo. These data may help to better understand the cause of the autoimmune processes leading to autoimmune AD. They extend our very limited knowledge concerning miRNAs in autoimmune Addison's disease.

HLA-A2 phenotype may be protective against Graves' disease but not against Hashimoto's thyroiditis in Caucasians.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are the most common autoimmune thyroid diseases (AITDs) affecting up to 5% of the general population. In Caucasians HT has a prevalence of up to 4.60% and GD a prevalence of 1-2%. The aim of this study was to investigate the association between HLA-A2 and the AITDs GD and HT among Caucasians. HLA alleles of 33 patients with GD and 75 patients with HT were determined by serological typing. The frequency of HLA A2 was significantly reduced in GD (p=0.033) but not in HT (p=n.s.) as compared to control samples. In individuals positive for HLA-A2 odds ratio for protection from GD was found to be 2.8. This study supports the hypothesis that genetic predisposition to GD is not restricted to MHC class II molecules. The significant negative association between HLA A2 and GD supports the hypothesis that MHC class I genes may be relevant for the protection from GD. In contrast the nonsignificant results for HT indicate that this association may not apply to AITDs in general.

Griseofulvin inhibits the growth of adrenocortical cancer cells in vitro.

Supernumerary centrosomes and aneuploidy are associated with a malignant phenotype of tumor cells. Centrosomal clustering is a mechanism used by cancer cells with supernumerary centrosomes to solve the threatening problem of multipolar spindles. Griseofulvin is an antifungal substance that interferes with the microtubule apparatus and inhibits centrosomal clustering. It has also been demonstrated that griseofulvin inhibits the growth of tumor cells in vitro and in vivo. However, it is not yet known whether treatment with griseofulvin inhibits growth of adrenocortical tumor cells. We studied the viability and antiproliferative effects of griseofulvin on cultured NCI-H295R adrenocortical carcinoma cells using Wst-1-, BrdUrd-, and [³H]-thymidine assays. For the detection of apoptosis we used a caspase 3/7 cleavage assay and light microscopy techniques. We observed that incubation with griseofulvin for 24-48 h leads to a decrease in the viability and proliferation of NCI-H295R cells in a dose-dependent manner. Significant effects could be observed after incubation with griseofulvin as measured by Wst-1-, BrdUrd-, and [³H]dT- uptake assays. Apoptosis of NCI-H295R cells was increased in a dose-dependent manner up to 4.5-fold after incubation with griseofulvin 40 µM for 24 h as shown by caspase 3/7 cleavage assay and light microscopy. With regard to new treatment strategies for adrenocortical cancer, griseofulvin, and possibly other agents, which interfere with the microtubule apparatus and inhibit centrosomal clustering, may turn out to be interesting targets for further research.

Examination of orbital tissues in murine models of Graves' disease reveals expression of UCP-1 and the TSHR in retrobulbar adipose tissues.

Over the past decade a number of murine models of Graves' disease (GD) have been described. The full symptom complex, including typical orbital changes, however, could not yet be induced. In this report, we examined the influence of modified immunization protocols on orbital pathology. C57BL/6 and BALB/c mice were immunized against the human TSH receptor (TSHR), using either a TSHR encoding plasmid or a TSHR A-subunit adenovirus. Prior to immunization with the TSHR plasmid, regulatory T cells were depleted in one group of each strain. TSHR-stimulating antibodies (TSAbs) were evaluated and orbits were stained immunohistochemically for F4/80, uncoupling protein-1 (UCP-1) and the TSHR. We found that after depletion of regulatory T cells, incidence of TSAb was increased in TSHR plasmid immunized C57BL/6 mice. Examination of early immunized mice showed no antibody production. However, a TSHR epitope-specific cellular immune response could be detected by tetramer-analyses. Adenoviral immunization lead to TSAb production in all but one animal. Analysis of F4/80 positive cells in retrobulbar fat revealed no significant macrophage infiltration in the orbits of immunized mice. Immunohistochemical staining shows co-localization of F4/80 positive cells, UCP-1 and the TSHR in retrobulbar fat. Though targets for TSHR autoimmunity could clearly be shown, immunization methods were not efficient enough to cause clear signs of orbital inflammation.

[Subdural hematoma after dural puncture: fateful complication of epidural anesthesia]. / Subdurales Hämatom nach Duraperforation: Schicksalhafte Komplikation der Periduralanästhesie.

Subdural hematoma may occur as rare, although intervention- specific complications of accidental dural puncture by neuroaxial block. Bleeding may be caused by rapid cerebrospinal fluid loss related to traction on fragile intracranial bridging veins. This article reports a case of postdural puncture headache in a 43-year-old woman after accidental dural puncture during attempted placement of an epidural catheter for induction of abortion. Bed rest, analgesics, theophylline and hydration were to no avail and only a blood patch improved the headaches. The patient presented 7 weeks later with headache and left-sided hemiplegia. Magnetic resonance imaging showed a right frontoparietal subdural intracranial hematoma which had to be surgically evacuated. The patient recovered completely. Intracranial hematoma is a rare but serious complication of central neuroaxial block. According to current German jurisdiction this risk must be addressed when informed consent is obtained. Intracranial hematoma should be considered in the differential diagnosis of atypical headache and neurological signs (e.g. focal motor and sensory deficits and seizures) following neuroaxial block and adequate image diagnostics should be carried out without delay.

[Hyperthyroidism]. / Hyperthyreose.

Thyrotoxicosis is mainly caused by autonomous adenomas of the thyroid gland and by Graves' disease. A less frequent cause for thyrotoxicosis is Hashimoto's thyroiditis. Thyrotoxicosis in autonomous adenomas and Graves' disease is caused by an increased thyroid hormone production whereas hyperthyroidism in Hashimoto's thyroiditis results from destruction of the thyroid gland. Drug therapy depends on the cause of the disease. Autonomous adenomas and Graves' disease are treated with methimazole and potentially with ß-blockers. Regarding thyroid ablative therapy, radioiodine is mostly preferred compared to thyroidectomy. Drug therapy of Hashimoto's thyroiditis is purely symptomatic using ß-blockers and rarely corticosteroids. Hyperthyroidism in pregnancy is a major issue and pregnant women in the first trimester are treated with propylthiouracil (PTU) whereas women in the second and third trimesters are treated with methimazole. The aim is to maintain the serum fT4 levels within the upper normal range.

Filter feeders are key to small microplastic residence times in stratified lakes: A virtual experiment.

Microplastic (MP) is potentially harmful to lake ecosystems, with its uptake into the food web largely controlled by its residence time in the lake water column. Here we combine laboratory and virtual experiments to quantify residence times of small MP (<15 µm) in two contrasting model lakes; Lake Constance (large lake) and Esthwaite Water (a small lake). We compare MP residence times in a purely physical system with MP transport controlled by sinking and mixing to a model where, in addition to physical processes, zooplankton package MP into faecal pellets that are then egested into the water column. The laboratory experiments showed that MP settling velocities increased from ~5 × 10-6-10-3 mm s-1 for pristine MP to ~1 mm s-1 for MP embedded faeces. Modeled lake residence times for the 0.5 and 5 µm particles were >15 years in the abiotic models, while in the biotic simulations they were reduced to ~1 year. There was little difference between abiotic and biotic simulations for the 15 µm particles. The ratio of the MP zooplankton uptake velocity to the sinking velocity (v_up/vs_epi) was used to classify biological vs. physical transport pathways. For the 0.5 and 5 µm particles v_up/vs_epi was ≫1 in all cases for both lakes, while for the 15 µm MP there was a transition between biological and physical processes dominating residence times depending on zooplankton numbers. Our results suggest that packaging of small MP in faecal pellets by zooplankton will control its residence time in lakes. Moreover, the majority of small MP will cycle through organisms before reaching the sediment, increasing the likelihood of negative ecological effects and transfer in the food web.

Comparison of the saline infusion test and the fludrocortisone suppression test for the diagnosis of primary aldosteronism.

For the diagnosis of primary aldosteronism (PA), confirmatory testing is mandatory and different function tests can be employed. There are, however, sparse data comparing the fludrocortisone suppression test (FST) and the saline infusion test (SIT). Patients with PA (n=90) or essential hypertension (n=65) were studied. They underwent one or the other test or both of them. Using the DPC Siemens aldosterone radioimmunoassay, we found that the SIT led to a stronger suppression of aldosterone than the FST. Post-test aldosterone-to-renin ratios (ARRs) and the percentage of suppression of aldosterone serum concentrations performed worse. The same results were observed in patients who underwent both FST and SIT. Some patients had divergent results in both tests. For the SIT, a lower cutoff value should be used than for the FST for the adequate identification of patients with unilateral PA. Long-term prospective studies are needed to address the question at what cutoff values patients benefit from subtype differentiation of PA. We discuss here possible explanations for divergent results obtained with both tests.