[Vascular surgery in old people]. / Gefäßchirurgie bei alten Menschen.

The age pyramid in Germany is upside down. According to the Federal Statistical Office this development will continue in the coming years, which presents a challenge for surgeons to surgically treat increasingly more and increasingly older people. Particularly in vascular surgery, which is a surgery of old people, this fact represents a special challenge. The frailty of old people is, among other things, due to a series of comorbidities, which must be taken into consideration within the framework of surgical treatment. They can have an important influence on the perioperative planning, the operation, the postoperative treatment and the outcome of the patient. This treatment planning becomes more and more challenging, because due to the progress in endovascular surgery there will soon be no limits to what is feasible; however, the question arises whether the feasible is also reasonable? Within the scope of this article the authors try to give answers to the treatment of old patients in vascular surgery and to find strategies for planning and to establish an individualized optimal treatment.

Search Dynamics on Multimodal Multiobjective Problems.

We continue recent work on the definition of multimodality in multiobjective optimization (MO) and the introduction of a test bed for multimodal MO problems. This goes beyond well-known diversity maintenance approaches but instead focuses on the landscape topology induced by the objective functions. More general multimodal MO problems are considered by allowing ellipsoid contours for single-objective subproblems. An experimental analysis compares two MO algorithms, one that explicitly relies on hypervolume gradient approximation, and one that is based on local search, both on a selection of generated example problems. We do not focus on performance but on the interaction induced by the problems and algorithms, which can be described by means of specific characteristics explicitly designed for the multimodal MO setting. Furthermore, we widen the scope of our analysis by additionally applying visualization techniques in the decision space. This strengthens and extends the foundations for Exploratory Landscape Analysis (ELA) in MO.

A clickable NHC-Au(i)-complex for the preparation of stimulus-responsive metallopeptide amphiphiles.

We report the synthesis of an alkyne functionalised NHC-Au(i)-complex which is conjugated with amphiphilic oligopeptides using a copper(i) catalysed cycloaddition. The resulting Au(i)-metalloamphiphiles are shown to self-assemble into charge-regulated stimulus-responsive supramolecular polymers in water via a weakly cooperative polymerisation mechanism.

A high-strength silicide phase in a stainless steel alloy designed for wear-resistant applications.

Hardfacing alloys provide strong, wear-resistant and corrosion-resistant coatings for extreme environments such as those within nuclear reactors. Here, we report an ultra-high-strength Fe-Cr-Ni silicide phase, named π-ferrosilicide, within a hardfacing Fe-based alloy. Electron diffraction tomography has allowed the determination of the atomic structure of this phase. Nanohardness testing indicates that the π-ferrosilicide phase is up to 2.5 times harder than the surrounding austenite and ferrite phases. The compressive strength of the π-ferrosilicide phase is exceptionally high and does not yield despite loading in excess of 1.6 GPa. Such a high-strength silicide phase could not only provide a new type of strong, wear-resistant and corrosion-resistant Fe-based coating, replacing more costly and hazardous Co-based alloys for nuclear applications, but also lead to the development of a new class of high-performance silicide-strengthened stainless steels, no longer reliant on carbon for strengthening.

Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells.

PURPOSE: Patients with advanced and metastasized medullary thyroid carcinoma are difficult to treat since tumor cells do not respond to chemotherapeutic treatment and external radiation. Direct induction of cell death is a new therapeutic approach to therapy-resistant tumor cells. In this study we analyzed the effect of the indirubin-derivative 7BIO and the BH3 mimetic drugs ABT-737 and GX15-070 on cell death induction of TT medullary thyroid carcinoma cells. METHODS: TT medullary thyroid carcinoma cell line was treated with 7BIO, ABT-737 and GX15-070. Cell viability was analyzed by MTT assay, while cell death was determined by caspase 3/7 activity, measurement of caspase cleavage products and lactate dehydrogenase liberation assay. LC3B cleavage was analyzed by western blot. RESULTS: Incubation with all 3 drugs efficiently decreased the number of viable TT cells with IC50 values of 4.1 µM (7BIO), 0.19 µM (ABT-737) and 0.23 µM (GX15-070). The BH3 mimetic ABT-737 caused an apoptotic cell death with caspase activation as expected, while 7BIO- and GX15-070-treatment led to a mixed kind of cell death, where caspase activation was detected but had no effect on viability of TT cells. LC3 conversion as a biochemical marker of autophagic cell death was observed after GX15-070 treatment while LDH release pointed to involvement of necrosis after treatment with all 3 drugs. CONCLUSION: The BH3 mimetic drugs ABT-737 and GX15-070 efficiently killed TT medullary thyroid carcinoma cells with low IC50 values, while the indirubin-derivative 7BIO was also effective but with a higher IC50 value. Although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells.

[Reconciling activities of working women providing care and the influence of structural and cultural factors]. / Vermittlungshandlungen erwerbstätiger pflegender Frauen und der Einfluss struktureller und kultureller Rahmenbedingungen.

BACKGROUND: Today, an increasing proportion of society has to reconcile eldercare and work. This task poses challenges for them, which they meet through an adjustment of their everyday living arrangements. These coping strategies have been so far scarcely noted within research on the reconciliation of elder care and employment. Knowledge about the active dealing with this parallel involvement in both spheres of life is of vital importance when wanting to derive precisely tailored support measures for employed care givers. MATERIALS AND METHODS: A goal of this article is to deliver insight on reconciling activities of employed women who provide care, while it tries to specify respective factors which determine those actions. Moreover, an ideal typology is presented, which systematizes these associations. RESULTS: With this ideal typology, conceptual instruments have been developed which illustrate the complex reality of the reconciliation actions and the dependence on various coping resources. In gerontological practice, these findings may provide support to design an intervention strategy tailored to the individual situation that addresses the everyday level of action and strengthens the performance of those affected.

Adult long-term outcome of patients after congenital hydrocephalus shunt therapy.

INTRODUCTION: Even though shunt surgery has been an established and widely accepted treatment for congenital hydrocephalus for five decades, long-term follow-up and functional outcome data is rare. PATIENTS AND METHODS: Sixty-nine patients were examined after congenital hydrocephalus had been treated between 1971 and 1987 at the Department of Pediatric Surgery (University of Leipzig) within the first 12 months of life. Median age of patients was 32 years (range 25-42 years). Patients agreed to undergo a contemporary hydrocephalus assessment. RESULTS: Seven patients (10.1%) became shunt-independent before adulthood. By the age of 20, 82% of the patients had needed at least one shunt revision, 100% by the age of 30. 21.7% of the primary valves (Spitz-Holter) remained intact without revision until today up to 35 years (mean functional intactness 23 years). Shunt infections occurred in 4.3% of primary implantations. 48% of the patients had a good functional outcome (mRS = 0-1). 40.9% of the patients attended regular school. In summary, 75% patients work on a daily basis. 44.6% live an independent life, 35.4% rely on parental supervision, and 20% depend on professional care institutions. CONCLUSION: Compared to the pre-shunt era, surgery within the first year of life is advantageous regarding visual function, educational progress, and social results. The outcome achieved throughout childhood remains stable during adult life as long as catastrophic events of shunt malfunction can be prevented. Epilepsy, motor deficits, acute shunt dysfunction, and problems of social integration as well as aging parental caregivers seem to be prominent factors of morbidity in adulthood.

Expression of the cAMP binding protein EPAC1 in thyroid tumors and growth regulation of thyroid cells and thyroid carcinoma cells by EPAC proteins.

The thyrotropin receptor-cAMP pathway is central in growth regulation of thyroid cells and thyroid tumorigenesis, and it regulates expression of thyroid specific genes. Recently, 2 new protein kinase A-independent cAMP effectors named EPAC1 and 2 were described that activate additional intracellular pathways. The aim of our study was to investigate the role of EPAC proteins in growth regulation of thyroid cells and thyroid carcinomas. EPAC1 expression was investigated immunohistochemically in tissues of various thyroid tumors. Utilizing MTT assay, the effect of EPAC stimulation on proliferation in thyroid carcinoma cells and in non-transformed rat FRTL5 cells was investigated. The activation of intracellular signaling pathways was examined by RAP pull-down assay and Western blots. EPAC1 expression was strong in non-oxyphilic follicular thyroid adenomas and carcinomas and in follicular papillary thyroid carcinomas. It was moderate in oxyphilic follicular tumors and classical and tall cell papillary carcinomas. In contrast, EPAC1 expression was low in poorly differentiated carcinomas and very low in anaplastic carcinomas. Thyroid carcinoma cell lines showed no or very weak EPAC1 expression and exhibited no growth-promoting effect after EPAC stimulation. Non-transformed rat FRTL5 cells were growth-stimulated by an EPAC-specific cAMP-analogue and showed EPAC-dependent activation of RAP, ERK, and p70S6 kinase. EPAC1 expression and cellular response to EPAC activation in rat FRTL5 cells reflect cellular responses to cAMP and TSH stimulation in non-transformed thyroid cells. In undifferentiated thyroid carcinomas, loss of EPAC1 expression may be in accordance with the loss of thyroid-specific functions and the loss of responsiveness of the TSHR-cAMP pathway.

Analyzing the BBOB results by means of benchmarking concepts.

We present methods to answer two basic questions that arise when benchmarking optimization algorithms. The first one is: which algorithm is the "best" one? and the second one is: which algorithm should I use for my real-world problem? Both are connected and neither is easy to answer. We present a theoretical framework for designing and analyzing the raw data of such benchmark experiments. This represents a first step in answering the aforementioned questions. The 2009 and 2010 BBOB benchmark results are analyzed by means of this framework and we derive insight regarding the answers to the two questions. Furthermore, we discuss how to properly aggregate rankings from algorithm evaluations on individual problems into a consensus, its theoretical background and which common pitfalls should be avoided. Finally, we address the grouping of test problems into sets with similar optimizer rankings and investigate whether these are reflected by already proposed test problem characteristics, finding that this is not always the case.

Measurement of size-dependent composition variations for gamma prime (γ') precipitates in an advanced nickel-based superalloy.

Energy-dispersive X-ray (EDX) spectroscopy in the scanning transmission electron microscope (STEM) has been used to demonstrate the presence of size-dependent compositional variation for L12-structured Ni3Al-type gamma-prime (γ') precipitates within a commercial RR1000 Ni-based superalloy. This semi-quantitative elemental analysis has been achieved using electrochemical extraction of the γ' precipitates from the γ matrix. The applicability of this approach to size-dependent compositional analysis of precipitates was confirmed by a comparison of the size distribution for the extracted precipitates with those present in traditional electropolished foil specimens in the size range 20-250nm. By applying suitable thickness-dependent absorption-corrections we have demonstrated that the composition of γ' precipitates in our material depends on the size of the precipitate in the range of 5nm to 3µm. In particular, the Al content was observed to increase in smaller γ' precipitates while Ti and Ta contents are constant for all sizes of precipitate. Hf was observed to be present only in the largest precipitates. This type of local compositional information provides invaluable input to assess the accuracy of microstructural modelling for these complex alloys and provides new evidence supporting the importance of anti-site diffusion.

B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification.

BACKGROUND AND PURPOSE: B-type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP-associated risk results from coronary atherosclerosis or atrial fibrillation. METHODS: Three thousand six hundred and seventy five subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.6% men) without previous stroke, coronary heart disease, myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators were followed up over 110.1 ± 23.1 months. Cox proportional hazards regressions were used to examine BNP as a stroke predictor in addition to vascular risk factors (age, gender, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes, smoking), renal insufficiency, atrial fibrillation/known heart failure and coronary artery calcification. RESULTS: Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects suffering stroke had significantly higher BNP values at baseline than the remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001]. In a multivariable regression, log10 BNP was an independent stroke predictor [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24-3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P = 0.037) and computed-tomography-based log10 (coronary artery calcification + 1) (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women, both in subjects ≤65 and >65 years. In subsequent analyses, BNP discriminated the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367) origin. CONCLUSIONS: BNP predicts presumable cardioembolic stroke independent of coronary calcification.

A simplification and implementation of random-effects meta-analyses based on the exact distribution of Cochran's Q.

BACKGROUND: The random-effects (RE) model is the standard choice for meta-analysis in the presence of heterogeneity, and the standard RE method is the DerSimonian and Laird (DSL) approach, where the degree of heterogeneity is estimated using a moment-estimator. The DSL approach does not take into account the variability of the estimated heterogeneity variance in the estimation of Cochran's Q. Biggerstaff and Jackson derived the exact cumulative distribution function (CDF) of Q to account for the variability of τ^². OBJECTIVES: The first objective is to show that the explicit numerical computation of the density function of Cochran's Q is not required. The second objective is to develop an R package with the possibility to easily calculate the classical RE method and the new exact RE method. METHODS: The novel approach was validated in extensive simulation studies. The different approaches used in the simulation studies, including the exact weights RE meta-analysis, the I² and τ² estimates together with their confidence intervals were implemented in the R package metaxa. RESULTS: The comparison with the classical DSL method showed that the exact weights RE meta-analysis kept the nominal type I error level better and that it had greater power in case of many small studies and a single large study. The Hedges RE approach had inflated type I error levels. Another advantage of the exact weights RE meta-analysis is that an exact confidence interval for τ² is readily available. The exact weights RE approach had greater power in case of few studies, while the restricted maximum likelihood (REML) approach was superior in case of a large number of studies. Differences between the exact weights RE meta-analysis and the DSL approach were observed in the re-analysis of real data sets. Application of the exact weights RE meta-analysis, REML, and the DSL approach to real data sets showed that conclusions between these methods differed. CONCLUSIONS: The simplification does not require the calculation of the density of Cochran's Q, but only the calculation of the cumulative distribution function, while the previous approach required the computation of both the density and the cumulative distribution function. It thus reduces computation time, improves numerical stability, and reduces the approximation error in meta-analysis. The different approaches, including the exact weights RE meta-analysis, the I² and τ² estimates together with their confidence intervals are available in the R package metaxa, which can be used in applications.

Updated physiology and pathophysiology of CSF circulation--the pulsatile vector theory.

INTRODUCTION: Hydrocephalus is still a not well-understood diagnostic and a therapeutic dilemma because of the lack of sufficient and comprehensive model of cerebrospinal fluid circulation and pathological alterations. CONCLUSIONS: Based on current studies, reviews, and knowledge of cerebrospinal fluid dynamics, brain water dynamics, intracranial pressure, and cerebral perfusion physiology, a new concept is deducted that can describe normal and pathological changes of cerebrospinal fluid circulation and pathophysiology of idiopathic intracranial hypertension.

The use of 5-aminolevulinic acid fluorescence guidance in resection of pediatric brain tumors.

INTRODUCTION: Whereas in the adult population 5-Aminolevulinic acid (5-ALA) fluorescence guidance has been widely accepted for improving the extent of tumor resection, the application in children remains an off-label use. Even though most pediatric study protocols require a complete resection for improving outcome parameters, only few pediatric patients have been operated with fluorescence guidance, and it remains questionable, whether and which pediatric tumors show useful fluorescence. We present casuistic reports of application of 5-ALA in children collected from three different neurosurgical departments. PATIENTS AND METHODS: In children with suspected malignant intracerebral tumor or recurrence, individual informed consent was obtained in each case from the parents. 5-ALA was administered according to the adult protocol, with 20 mg/kg, 2 h before induction of anesthesia. We retrospectively analyzed 18 patients (13 male, 5 female; age 3-18 years), using the intraoperative neurosurgical protocol, the postoperative MRI results, and the follow-up clinical examinations. RESULTS: The use of 5-ALA fluorescence guidance proved to be safe in our group of pediatric patients. Fluorescence guidance was most useful for recurrent glioblastoma resection. Medulloblastoma tissue displayed fluorescence only inconsistently, and most pilocytic astrocytoma remained without staining. Ganglioglioma showed partial staining in the central tumor areas, without allowing the use for circumferent resection. CONCLUSION: The off-label use of 5-ALA fluorescence guidance in pediatric patients appears to be most useful in recurrent high-grade gliomas. Fluorescence accumulation in other pediatric brain tumor entities is not predictable and should be evaluated in future clinical studies before being integrated into the current treatment protocols.

Acute two-compartment low pressure hydrocephalus--a case report.

A case of an 8-year-old-boy with shunt-dependent occlusive hydrocephalus after resection of a cerebellar medulloblastoma is presented, who experienced repeated episodes of severe neurologic deterioration with signs and symptoms of raised intracranial pressure after spinal tapping. However, intracranial pressure was recorded within low ranges, only up to the opening pressure of the implanted adjustable shunt valve. Multiple shunt revisions were performed, until the condition was recognized as acute normal pressure hydrocephalus. Either enforced recumbency and downadjustment of the valve system to 0 cm H(2)O alone or external ventricular drainage seems to be successful to resolve the critical condition, depending on severity of the symptoms. The case illustrates that acute pathologic enlargement of the ventricular system is not always associated with increased intracranial pressure, even when typical signs and symptoms are present. The very rare entity of acute normal pressure hydrocephalus by two separated compartments is postulated based on the pulsatile vector force theory of brain water circulation.

Cardiac risk in patients with treatment naïve, first-line medically controlled and first-line surgically cured acromegaly in comparison to matched data from the general population.

INTRODUCTION: Coronary risk factors in patients with acromegaly after first-line transsphenoidal surgery (TSS) or first-line somatostatine analogue (SSA) treatment have rarely been examined. Aim of this study was an evaluation of cardiovascular risk factors and left ventricular hypertrophy (LVH) in 3 different patient groups with treatment naïve, active (ACT), first-line medically controlled (MED) and first-line surgically treated (SUR) acromegaly and a calculation of the Framingham Weibull Risk Score (FS). DESIGN: Retrospective comparative matched case-control study. PATIENTS & METHODS: 40 acromegalic patients (cases aged 45-74 years, 23 men) were matched with respect to age and gender to 200 controls from the general population. 13 patients had treatment-naïve acromegaly (ACT), 12 patients were SSA treated (MED) and 15 patients were operated by TSS (SUR). Coronary risk factors were assessed after 12 months of treatment by interviews and direct laboratory measurements. Only patients normalized for IGF-I in MED and SUR group were included. FS and odds ratios (OR) from multiple conditional logistic regression (matched for age and gender, adjusted for BMI) were calculated. RESULTS: Compared to matched controls ACT patients had higher HbA1c levels (6.9±1.4 vs. 5.5±0.7% (p<0.0001)) and an increased prevalence of left ventricular hypertrophy (LVH) (30.8 vs. 3.2% (p=0.007). MED and SUR groups were similar for gender, age, disease duration and IGF-I levels at diagnosis. Compared to matched controls, MED patients had a significantly increased diastolic blood pressure (89±9 vs. 79±11 mmHg (p=0.001), prevalence of LVH (41.7 vs. 1.7% (p<0.0001), prevalence of diabetes mellitus (33.3 vs. 10.0% (p=0.03)), higher HbA1c levels (6.8±1.3 vs. 5.5±0.7% (p=0.0005)) and a higher FS (21.2±9.7 vs. 12.4±7.7% (p=0.002), OR 1.11 [1.02-1.21] (p=0.01)) while in the SUR group only higher prevalences of LVH (40.0 vs. 4.1% (p<0.0001)) and HbA1c levels (6.4±1.2 vs. 5.5±0.8% (p=0.006)) were found compared to controls. CONCLUSION: When comparing treatment naive, medically treated and surgically cured patients with acromegaly to age- and gender-matched subjects from the general population, we have found an increased cardiovascular risk in patients at 12 months after first-line SSA treatment but not in patients after first-line surgery.

Effectiveness of bevacizumab for radiation-induced cerebral necrosis in children.

INTRODUCTION: Bevacizumab has been reported to effectively reduce cerebral edema caused by radiation therapy. However, only limited data with a short follow-up in tumor patients are available so far. PATIENTS AND METHODS: Two children suffering from hemorrhage from arteriovenous malformation (AVM) have been treated with stereotactic radiotherapy and developed radiation-induced cerebral edema with deteriorating neurological status despite maximized steroid therapy. Bevacizumab administration at 5 mg/kg body weight was initiated every 2 weeks. RESULTS: Bevacizumab treatment rapidly ameliorated the neurological deficits, malignant edema and prevented catastrophic complications. Corticoid therapy could be reduced and discontinued. However, after 18 months, both patients showed identical or worse neurological status than before bevacizumab therapy. AVM radiation therapy had been successful to completely obliterate AVMs. DISCUSSION: In our limited experience, bevacizumab may be an effective and safe option for rescue therapy for malignant cerebral edema on the basis of radiation-induced necrosis especially in patients who experience rapid deterioration despite corticoid therapy and/or intolerable steroid side effects. Despite the fact that functional improvement could not be achieved in long-term outcome patients significantly stabilized and improved during periods of acute deterioration. In order to determine the long-term effectiveness of bevacizumab further investigation in placebo-controlled studies with a higher number of patients are required.

Experimental studies of Debye-like process and structural relaxation in mixtures of 2-ethyl-1-hexanol and 2-ethyl-1-hexyl bromide.

Binary solutions of 2-ethyl-1-hexanol (2E1H) with 2-ethyl-1-hexyl bromide (2E1Br) are investigated by means of dielectric, shear mechanical, near-infrared, and solvation spectroscopy as well as dielectrically monitored physical aging. For moderately diluted 2E1H the slow Debye-like process, which dominates the dielectric spectra of the neat monohydroxy alcohol, separates significantly from the α-relaxation. For example, the separation in equimolar mixtures amounts to four decades in frequency. This situation of highly resolved processes allows one to demonstrate unambiguously that physical aging is governed by the α-process, but even under these ideal conditions the Debye process remains undetectable in shear mechanical experiments. Furthermore, the solvation experiments show that under constant charge conditions the microscopic polarization fluctuations take place on the time scale of the structural process. The hydrogen-bond populations monitored via near-infrared spectroscopy indicate the presence of a critical alcohol concentration, x(c) ≈ 0.5-0.6, thereby confirming the dielectric data. In the pure bromide a slow dielectric process of reduced intensity is present in addition to the main relaxation. This is taken as a sign of intermolecular cooperativity probably mediated via halogen bonds.

[Influence of the calcitonin assay on the definition of biochemical cure in patients with medullary thyroid carcinoma]. / Assay-Abhängigkeit der Calcitonin-Zielbereiche für "biochemisch geheilte" Patienten mit medullärem Schilddrüsenkarzinom.

AIM: Calcitonin (hCT) is an important diagnostic parameter in medullary thyroid carcinoma (MTC). We determined the variability of the reference ranges of several currently available immunometric assays for "biochemically cured" MTC patients. PATIENTS, METHODS: We compared six assays [Nichols ICMA, Biomerica IEMA, Immulite 2000 (Siemens), Calcitonin-IRMA magnum (Medipan), SELco-IRMA (Medipan) and Calcitonin IRMA (Medgenix)] in subgroups of 198 patients with differentiated thyroid cancer (DTC) after total thyroidectomy as a model for curatively treated MTC patients. In addition, hCT was measured after pentagastrin stimulation in 13 DTC patients and 13 patients with MTC. RESULTS: The basal hCT concentrations were below the detection limit of the respective assay in 100% of all thyroidectomized DTC patients for Nichols ICMA (n = 138) and Immulite 2000 (n = 60), in 97% for Biomerica IEMA (n = 57), and in 85% for IRMA magnum (n = 20). However, basal hCT was mostly within the reference range in Selco-IRMA (n = 20) and Medgenix IRMA (n = 76). In all DTC patients and 9/13 MTC patients the pentagastrin stimulated hCT was below the detection limit for the Nichols ICMA and Immulite 2000, all four MTC patients with elevated stimulated hCT developed a recurrence during follow-up. CONCLUSIONS: For assays with high monomer specificity (Nichols ICMA, Biomerica IEMA, Immulite 2000, to a lesser degree IRMA magnum) biochemical cure is defined by basal and stimulated calcitonin levels below the detection limit. For assays with low monomer specificity (SELco-IRMA, IRMA Medgenix) calcitonin levels in the reference range of patients without thyroid diseases are consistent with "biochemical cure".