[Thyroid emergencies : Thyroid storm and myxedema coma]. / Schilddrüsennotfälle : Thyreotoxische Krise und Myxödemkoma.

Thyroid emergencies are rare life-threatening endocrine conditions resulting from either decompensated thyrotoxicosis (thyroid storm) or severe thyroid hormone deficiency (myxedema coma). Both conditions develop out of a long-standing undiagnosed or untreated hyper- or hypothyroidism, respectively, precipitated by an acute stress-associated event, such as infection, trauma, or surgery. Cardinal features of thyroid storm are myasthenia, cardiovascular symptoms, in particular tachycardia, as well as hyperthermia and central nervous system dysfunction. The diagnosis is made based on clinical criteria only as thyroid hormone measurements do not differentiate between thyroid storm and uncomplicated hyperthyroidism. In addition to critical care measures therapy focusses on inhibition of thyroid hormone synthesis and secretion (antithyroid drugs, perchlorate, Lugol's solution, cholestyramine, thyroidectomy) as well as inhibition of thyroid hormone effects in the periphery (ß-blocker, glucocorticoids).Cardinal symptoms of myxedema coma are hypothermia, decreased mental status, and hypoventilation with risk of pneumonia and hyponatremia. The diagnosis is also purely based on clinical criteria as measurements of thyroid hormone levels do not differ between uncomplicated severe hypothyroidism and myxedema coma. In addition to substitution of thyroid hormones and glucocorticoids, therapy focusses on critical care measures to treat hypoventilation and hypercapnia, correction of hyponatremia and hypothermia.Survival of both thyroid emergencies can only be optimized by early diagnosis based on clinical criteria and prompt initiation of multimodal therapy including supportive measures and treatment of the precipitating event.

Developing Demonstration Test Catchments as a platform for transdisciplinary land management research in England and Wales.

Whilst a large body of plot and field-scale research exists on the sources, behaviour and mitigation of diffuse water pollution from agriculture, putting this evidence into a practical, context at large spatial scales to inform policy remains challenging. Understanding the behaviour of pollutants (nutrients, sediment, microbes and pesticides) and the effectiveness of mitigation strategies over whole catchments and long timeframes requires new, interdisciplinary approaches to organise and undertake research. This paper provides an introduction to the demonstration test catchments (DTC) programme, which was established in 2009 to gather empirical evidence on the cost-effectiveness of combinations of diffuse pollution mitigation measures at catchment scales. DTC firstly provides a physical platform of instrumented study catchments in which approaches for the mitigation of diffuse agricultural water pollution can be experimentally tested and iteratively improved. Secondly, it has established national and local knowledge exchange networks between researchers and stakeholders through which research has been co-designed. These have provided a vehicle to disseminate emerging findings to inform policy and land management practice. The role of DTC is that of an outdoor laboratory to develop knowledge and approaches that can be applied in less well studied locations. The research platform approach developed through DTC has brought together disparate research groups from different disciplines and institutions through nationally coordinated activities. It offers a model that can be adopted to organise research on other complex, interdisciplinary problems to inform policy and operational decision-making.

Hypophysitis caused by ipilimumab in cancer patients: hormone replacement or immunosuppressive therapy.

Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially approved medical treatment for metastatic melanoma, which results in improved survival. Ipilimumab leads to a release of a CTLA4-mediated inhibition of T-cell immunoreactions. Therefore, patients may also suffer from immune-related adverse events affecting different organs, which are typically treated by high-dose corticosteroids. Ipilimumab-induced hypophysitis (iH) has been reported in up to 17% of melanoma patients in clinical trials.Here we present 5 patients with metastatic melanoma and 2 patients with prostate cancer who developed hypophysitis after ipilimumab therapy. Patients were treated by high-dose corticosteroid therapy resulting in the resolution of local inflammation but not of pituitary deficiencies. Partial or complete hypopituitarism remained in all patients. Pharmacotherapy with high-dose corticosteroids caused complications in 5 patients, necessitating hospitalization in 4. 2 of the 3 patients with progressive disease died, while 3 patients had stable disease and 1 patient showed tumor regression after discontinuation of ipilimumab.In summary, with regard to safety and simplicity of hormonal substitution therapy we have to scrutinize high-dose corticosteroid therapy, though it only improves inflammation but not neuro-endocrine function and may cause further morbidity. Regression of the tumor depends on the ipilimumab-mediated immune events, in which high-dose and long-term corticosteroid therapy for iH appears to be counter-intuitive. Herein, we discuss screening and the diagnostic as well as therapeutic management of iH in metastatic cancer patients from an endocrinologic perspective.

[Thyroid hormone treatment]. / Schilddrüsenhormontherapie.

The autoimmune thyroiditis with overt or subclinical primary hypothyroidism is the most common endocrine disease. Although the diagnosis of hypothyroidism is not difficult, the question when a replacement therapy in subclinical hypothyroidism should be initiated is still under discussion. In patients with overt hypothyroidism defined as low FT4 and elevated TSH or TSH > 10 mU/L a replacement with levothyroxine is clearly indicated. In patients with subclinical hypothyroidism defined as a TSH between 4 and 10 mU/L and normal FT4, the treatment with Levothyroxine depends on the underlying disease and symptoms. Levothyroxine is a prohormone with is activated by deiodination in the organs to triiodothyronine. Therefore, levothyroxine for replacement therapy is mainly used. Some patients, however, do not feel well with this treatment and therefore studies with a combination therapy of levothyroxine and triiodothyronine had been performed and it could be shown that this might be related to a polymorphism in type 2 deiodinase in some patients, with the consequence of lower intracellular triodothyronine formation. In women on levothyroxine replacement therapy getting pregnant, the demand of levothyroxine increases up to 25-50 µg, especially in the early weeks of pregnancy. It also has to be considered that the resorption of levothyroxine depends on normal stomach acid and therefore patients on acid blockers or atrophic gastritis require higher dosages of levothyroxine. Only patients after thyroidectomy because of differentiated thyroid carcinoma with higher grad of malignancy need a TSH suppressive therapy, those with occult papillary thyroid carcinoma the TSH should be within the low normal range.

NSE and S-100B are not sufficiently predictive of neurologic outcome after therapeutic hypothermia for cardiac arrest.

INTRODUCTION: Prognostication of cardiac arrest survivors is challenging since therapeutic hypothermia (TH) has been introduced. We evaluated serum biomarkers and motor response. METHODS: This was a retrospective data analysis including patients in the years 2007-2012. Blood was drawn and a neurological examination was performed on admission and every morning. Outcomes were evaluated 6 months after discharge and dichotomized into good (cerebral performance category (CPC)=1 or 2) and poor (CPC=3, 4 or 5). RESULTS: 123 patients (79.7% male, 63±14 years) received TH; 50% had a good outcome. On admission, S-100B (P=0.004) was significantly associated with the outcome, as well as neuron-specific enolase (NSE; P=0.020) and S-100B (P=0.004) on day 1 after admission. NSE on day 2, NSE progression from day 1 to 2 and motor response on day 3 also predicted the outcome (all P<0.001). NSE>33µgl(-1) only predicted a poor outcome with a specificity of 76%. An absent motor response on day 3 was the most sensitive marker (94%). NSE>41.1µgl(-1) combined with S-100B>0.461µgl(-1) on day 1 was the most specific marker (96%). CONCLUSION: Although NSE and S-100B levels are associated with the outcome, the use of previously described cut-off values was insufficiently predictive of neurologic outcome. Caution should be exercised in the use of these tests to provide neuroprognostication.

Persistent pain, sensory disturbances and functional impairment after immediate or delayed axillary lymph node dissection.

BACKGROUND: Patients treated with 2-step axillary lymph node dissection (ALND) may be at increased risk of nerve damage due to more challenging surgery than an ALND immediately after a sentinel lymph node biopsy (SLNB), and thus more at risk for persistent pain after breast cancer treatment (PPBCT). The aim of this study was to examine PPBCT, sensory disturbances and functional impairment in patients treated with a 2-step ALND compared to patients with an SLNB followed by an immediate ALND, and patients with ALND without a prior SLNB. METHODS: The study is a cross-sectional questionnaire study, comparing 2847 women treated with ALND in Denmark in 2005-2008. 196 patients treated with a 2-step ALND were compared with 1558 patients treated with an ALND after SLNB and 1093 with an ALND without a prior SLNB. RESULTS: Overall prevalence of PPBCT and sensory disturbances was high, with about 55% reporting PPBCT and 77% reporting sensory disturbances in all groups. No differences were found between the groups on prevalence and intensity of PPBCT (p = 0.92), sensory disturbances (p = 0.32), and functional consequences (p = 0.35). CONCLUSIONS: A 2-step ALND does not modify the risk of developing PPBCT compared to an immediate ALND.

Micronutrients in pregnancy: current knowledge and unresolved questions.

Micronutrient status is increasingly recognized to play an important role in the health and well-being of pregnant women and in the development and long-term health of the offspring. On 26th - 28th February 2009, The Child Health Foundation invited leading experts in this area to a scientific workshop at Obergurgl, Austria to review and critically discuss current knowledge, to identify issues that may need to be addressed in future recommendations, and to highlight priorities and opportunities for future research. This report summarizes updated key conclusions of the workshop with regards to micronutrients' intake and physiological role related to mother, placenta and fetus, as well as relevance for adverse pregnancy and long-term outcomes.

Multimodal prevention of pain, nausea and vomiting after breast cancer surgery.

BACKGROUND: Despite many one- or two-modal attempts to relieve postoperative nausea and vomiting (PONV) and pain, postoperative issues following breast cancer surgery remain a substantial problem. Therefore, the aim of this explorative, hypothesis-generating study was to evaluate the effect of a multimodal, opiate-sparing, evidence-based regimen for prevention of PONV and pain. METHODS: Two hundred consecutive patients scheduled for breast cancer surgery were included. The prevention regimen included a package consisting of preoperative paracetamol, dextromethorphan, celecoxib, gabapentin, dexamethasone, total intravenous anaesthesia and intraoperative ondansetron. The patients were prospectively scored according to PONV, pain during rest and mobilization and major side effects. RESULTS: Of 200 consecutive breast cancer patients, 191 received the full package. During the first 36 postoperative hours, 79.1% reported no PONV at all and only 3.7% reported severe PONV. At rest, 69.6% reported no or light pain and 3.1% reported severe pain, with corresponding values of 59.7% and 8.9% during arm mobilization. Mean postoperative morphine consumption was 2.2 mg. The only significant side effect was transient dizziness. CONCLUSION: A multimodal, opiate-sparing regimen to prevent pain and PONV seems to be more effective than one- or two-component regimens on PONV and pain after breast cancer surgery, a result which calls for large-scale multi-center or randomized studies.

[Iodine deficiency in infancy - a risk for cognitive development]. / Jodmangel im Säuglingsalter - ein Risiko für die kognitive Entwicklung.

Severe iodine deficiency during pregnancy seriously influences fetal brain development and in the worst case induces cretinism. Recent studies have shown that even a mild iodine deficiency during pregnancy and during the first years of life adversely affects brain development. The World Health Organisation (WHO) considers iodine deficiency as the most common preventable cause of early childhood mental deficiency. In this context, the insufficient production of the four iodine atoms containing thyroxine seems to play a causal role, i. e., due to the iodine substrate deficiency the neuronally particularly relevant free-thyroxine level falls. Due to the very limited iodine storage capacity, the infantile thyroid is eminently dependent on an adequate and steady iodine supply. In the first month of life, when milk is the only energy- and nutrient provider, infants fed a commercial formula regularly have a sufficient iodine supply. However, breastfed infants, who depend on maternal iodine status, frequently show an inadequate iodine intake. Furthermore, iodine intake is critical when complementary food (CF) is introduced. Especially homemade CF is poor in iodine, but also commercial CFs are only partly fortified. A simultaneous inadequate iodine supply of the breastfeeding mother and the preferential use of mostly iodine-poor organic milk cannot ensure an adequate iodine supply of the infant. In terms of an improvement of nutrient supply, especially concerning an unhindered brain development, the corresponding German reference value for iodine intake of infants until age 4 month should be raised from currently 40 microg/d to at least 60 microg/d (WHO-reference: 90 microg/d).

Selenium supplementation does not decrease thyroid peroxidase antibody concentration in children and adolescents with autoimmune thyroiditis.

In adults, selenium supplementation decreases thyroid peroxidase antibody (TPO Ab) concentrations in patients with autoimmune thyroiditis (AIT). Our aim in this study was to investigate if selenium supplementation decreased TPO Ab and thyroglobulin antibody (Tg Ab) concentrations in children with AIT. Forty-nine patients (33 females) with newly diagnosed AIT and hypothyroidism were randomized to daily oral therapy with levothyroxine alone (group A, n=18), levothyroxine plus 100 microg sodium-selenite (group B, n=13), or levothyroxine plus 200 microg sodium-selenite (group C, n=18). Mean age at diagnosis was 12.2+/-2.2 years. All 49 patients needed a mean levothyroxine dose of 1.6+/-0.5 microg/kg body weight to lower TSH to the treatment goal of 1-2 microU/ml, with no significant difference between groups. At study entry and after 12 months, TPO Ab concentrations were comparable in all three groups. Tg Ab concentrations decreased significantly after 12 months in group A and group C (p=0.03 and p=0.01), but not in group B (p=0.06). It is our conclusion that selenium supplementation with sodium-selenite does not decrease TPO Ab concentrations in children and adolescents, neither given in the reduced dose of 100 microg daily nor given in the "adult" supplementation dose of 200 microg daily.

Comparison of Color Flow Doppler Sonography (CFDS) and immunohistologic detection of microvessels for the assessment of the malignancy of thyroid nodules.

The assessment of tumor vascularization by color flow Doppler sonography (CFDS) has been suggested for the distinction between benign and malignant thyroid nodules. Our objective was to investigate if the CFDS results reflect the percentage of histologically determined microvessels in adenomas (As), adenomatous nodules (ANs), and papillary carcinomas (PCs). Tissue sections from 10 adenomas, 8 ANs and 13 PC and surrounding tissue of 10 PCs and 2 benign nodules were immunostained for CD34. A computerized image analysis was used to determine the microvessel density in four hot spots and ten systematically selected fields. Preoperatively CFDS was performed and classified according to Frates et al. We found a consistent percentage increase of CD34 stained microvessels in PCs (83 and 96%) as compared to adenomas and ANs (38 and 49%) determined by the hot spot analysis and systematic field analysis. A ROC analysis on the basis of the histologically determined number of microvessels demonstrated 70% microvessels as an optimal cut point for the diagnosis of PC with the highest sensitivity of 92% and highest specificity of 89%. The analysis of the CFDS-classification IV for the distinction between PCs and adenomas and ANs showed a sensitivity of 62% with a specificity of 100%. The lower sensitivity of the CFDS classification as compared with the immunohistologic determination of the microvessel density indicates that the CFDS classification detects the pathognomonic intranodular microvessels only incompletely. The higher CFDS specificity is most likely due to the detection of other vascular aspects of malignancy in addition to intranodular microvessels.

[Flexible laryngeal mask airway use during surgical burn management with head mobilisation: a feasibility study]. / Intérêt du masque laryngé renforcé au cours de la chirurgie réparatrice chez les patients brûlés nécessitant une mobilisation de la tête : étude de faisabilité.

OBJECTIVE: To evaluate the feasibility and reliability of the flexible laryngeal mask airway (LMA flexible) use during scalp skin harvesting for surgical reparation of burn sequella. STUDY DESIGN: Observational prospective descriptive study. PATIENTS AND METHODS: Following local ethic committee approval, 26 patients were included in the study during their preanaesthesia visit. The general anaesthesia induction of each patient was followed by the insertion of a LMA flexible. The number of attempts required to insert the mask and the procedure were documented. The oropharyngeal leak pressure, expired tidal volume and end tidal CO(2) were recorded in five different head positions (neutral, hyperflexion, hyperextension, right and left rotation) at the start and end of surgical procedure. In all ten study periods of 2-3 min each were evaluated. RESULTS: The airway device was inserted easily in all patients. While similar in four of the five head positions (neutral: 27.9+/-8.1 cmH(2)O, hyperextension, left and right rotation), the oropharyngeal leak pressure was significantly higher in the hyperflexion position (33.3+/-7.3 cmH(2)O). The end tidal volume was stable in all positions except hyperflexion (419+/-114 ml). While this value was significantly lower than the 471+/-68 ml recorded in the neutral position, it remained greater than 7 ml/kg. No significant change was observed for end tidal CO(2) for the ten study periods. CONCLUSION: The use of LMA flexible during surgical burn repair procedures, including head mobilisation for the harvesting of scalp skin grafts is feasible.

Antiproliferative/cytotoxic activity of molecular iodine and iodolactones in various human carcinoma cell lines. No interfering with EGF-signaling, but evidence for apoptosis.

Twelve human cancer cell lines and one non-malignant cell line were investigated with respect to a potential antiproliferative/cytotoxic activity of molecular iodine and iodolactones. Except CCL221 colon carcinoma cells, the growth of all cancer cell lines decreased if the cells were cultured in the presence of 10 microM molecular iodine (I(2)) for at least two days. delta-iodolactone (IL, 5 microM) was found to have a similar effect. SH-SY5Y neuroblastoma cells turned out to be most susceptible to both iodine compounds (total inhibition), followed by MCF-7 mammary carcinoma cells (60% and 77.7% inhibition in the presence of I(2) respect. IL) and HS24 lung carcinoma cells (36.3% respect. 40.3% inhibition). In contrast, MCF-10 normal mammary epithelial cells were much less affected by the iodine treatment. In both, SH-SY5Y and MCF-7 cells, I(2) and IL also abolished EGF-induced promotion of cell growth completely. This effect was, however, not due to an interfering with EGF-signaling, because I(2) and IL did not affect the phosphorylation of EGF-receptors, EGF-induced activation of MAP-kinase (Erk(1/2)), or EGF-induced lamellar actin protrusion. A disruption by molecular iodine of mitochondrial transmembrane electrical potential, which was prevented by a pre-treatment of the cells with N-acetyl-cysteine, supports a mitochondria-mediated apoptotic mechanism.