Measurement of anti-TSH receptor antibodies: what is the correct cut-off value?

BACKGROUND: Autoantibodies against the thyroid stimulating hormone receptor, thyrotropin receptor autoantibodies (TRAb) are diagnostic for Graves' disease and can be measured by different methods. As antibody concentrations are not comparable between methods, appropriate cut-off values need to be established for every single method. For a third-generation TRAb assay (Phadia, Thermofisher), the manufacturer determined the cut-off value in a study population consisting of Graves' disease (both newly diagnosed and patients under treatment) and non-Graves' disease patients. The aim of this study was to verify whether this cut-off value holds true in our population. METHODS: Retrospective analysis was performed on TRAb measurements collected over a period of six months from all patients referred for TRAb testing. For our study, we included patients that were newly diagnosed with hyperthyroidism including Graves' disease, multinodular goitre, toxic adenoma, and thyroiditis. Furthermore, we included Graves' patients that were under treatment at the time of TRAb measurement. RESULTS: Whereas all patients with Graves' disease had positive TRAb, few patients with multinodular goitre, toxic adenoma, and thyroiditis scored positive for TRAb. ROC curve analysis revealed a cut-off value of 4.5 IU/l (compared to 3.3 IU/l established by the manufacturer). Newly diagnosed Graves' patients had higher TRAb concentrations compared to patients under treatment. CONCLUSION: The cut-off value of this immunoassay should probably be set higher in untreated Graves' patients than proposed by the manufacturer as the cut-off value should be determined in a study population excluding Graves' patients under treatment. The overall clinical picture remains crucial in the diagnosis of Graves' disease.

Optimization of laboratory procedures for intrauterine insemination: survey of methods in relation to clinical outcome.

BACKGROUND: There is a wide practice variation of used methods and outcomes in IUI in fertility laboratories. Standardization of the IUI procedure is important for reducing inconsistency among laboratories in counseling infertile couples and in pregnancy results. The aim of the study was to evaluate the currently used laboratory procedures of IUI in Dutch fertility laboratories and their effect on IUI pregnancy results. Additionally, the methods for semen analysis (SA) were evaluated, as SA is related to IUI in terms of inseminated sperm number and IUI counseling. MATERIAL AND METHODS: This questionnaire survey study was sent to laboratories participating in the Dutch external quality control program for semen analysis (SKML) and consisted of 46 questions concerning laboratory management, methods for semen analysis and IUI, and clinical results. The results were analyzed using univariable and multivariable logistic regression models. RESULTS: A total of 52 laboratories (out of 99) provided information on used methodologies for SA or laboratory procedures of IUI and the organization of the laboratory. A wide variability was confirmed in used methods for both SA and IUI. Evaluation of pregnancy results obtained during 3 years (2013-2015) showed that specific used laboratory methods have a significant effect on the probability of becoming pregnant. DISCUSSION AND CONCLUSION: Important to remark is that in this survey study cycle-specific data, including variables of the individual couples (age, stimulation protocol, etc), were not included and may have effects on the results. The reported results provide an overview of the current practice performance; however, the organization of fertility laboratories is changing rapidly. The use of standardized methods in IUI is important for optimizing the performance of care and improving pregnancy results. The knowledge on used procedures, however, is limited, and further research on factors involving SA and the IUI procedure is necessary.

Techniques used for IUI: is it time for a change?

STUDY QUESTION: Are the guidelines for the technical aspects of IUI (WHO, 2010) still in accordance with the current literature? SUMMARY ANSWER: In general, the laboratory guidelines of the World Health Organization (WHO) are a suitable protocol, although the evidence is not always conclusive and some changes are advisable. WHAT IS KNOWN ALREADY: Lack of standardization of the technical procedures required for IUI might result in inter-laboratory variation in pregnancy rates. Most centers still use their own materials and methods even though some guidelines are available. STUDY DESIGN, SIZE, DURATION: A structural review focusing on the association between pregnancy rates and the procedures of semen collection (e.g. ejaculatory abstinence, collection place), semen processing (e.g. preparation method, temperature during centrifugation/storage), insemination (e.g. timing of IUI, bed rest after IUI) and the equipment used. PARTICIPANTS/MATERIALS, SETTING, METHODS: A literature search was performed in Medline and the Cochrane library. When no adequate studies of the impact of a parameter on pregnancy results were found, its association with sperm parameters was reviewed. MAIN RESULTS AND THE ROLE OF CHANCE: For most variables, the literature review revealed a low level of evidence, a limited number of studies and/or an inadequate outcome measure. Moreover, the comparison of procedures (i.e. semen preparation technique, time interval between semen, collection, processing and IUI) revealed no consensus about their results. It was not possible to develop an evidence-based, optimal IUI treatment protocol. LIMITATIONS, REASONS FOR CAUTION: The included studies exhibited a lack of standardization in inclusion criteria and methods used. WIDER IMPLICATIONS OF THE FINDINGS: This review emphasizes the need for more knowledge about and standardization of assisted reproduction technologies. Our literature search indicates that some of the recommendations in the laboratory guidelines could be adapted to improve standardization, comfort, quality control and to cut costs. STUDY FUNDING/COMPETING INTEREST(S): The Dutch Foundation for Quality Assessment in Medical Laboratories (SKML), Nijmegen, The Netherlands. S.K. and W.N. have no conflicts of interest to disclose. C.B. and A.W. are members of the board of the SKML. With a grant from SKML, L.L. was paid for her time to perform the research and write the publication. D.B. received grants from Merck Serono, Ferring and MSD, outside the submitted work. REGISTRATION NUMBER: N/A.

Displacement of malignant cells into the portal triad of the liver results in reduced liver perfusion, mimicking segmental Fatty liver.

Liver steatosis is often observed in different clinical situations. Oncological patients undergoing systemic therapy often develop liver steatosis, which can be diagnosed with normal routine scans such as CT and ultrasound. In this case report, we show that an isolated infiltration of the portal triad with tumor cells could mimic a fatty-like infiltration of the liver. Radiologists and clinicians should be aware of this pitfall and should perform a biopsy in cases of doubt.

Challenges in diagnosing extrapulmonary tuberculosis in the European Union, 2011.

In the European Union (EU) 72,334 tuberculosis (TB) cases were notified in 2011, of which 16,116 (22%) had extrapulmonary tuberculosis (EPTB). The percentage of TB cases with EPTB ranged from 4% to 48% in the reporting countries. This difference might be explained by differences in risk factors for EPTB or challenges in diagnosis. To assess the practices in diagnosis of EPTB we asked European Union/European Economic Area (EU/EEA) countries to participate in a report describing the diagnostic procedures and challenges in diagnosing EPTB. Eleven EU Member States participated and reports showed that in the majority EPTB is diagnosed by a pulmonologist, sometimes in collaboration with the doctor who is specialised in the organ where the symptoms presented. In most countries a medical history and examination is followed by invasive procedures, puncture or biopsy, to collect material for confirmation of the disease (by culture/histology/cytology). Some countries also use the tuberculin skin test or an interferon-gamma-release-assay. A wide variety of radiological tests may be used. Countries that reported challenges in the diagnosis of EPTB reported that EPTB is often not considered because it is a rare disease and most medical professionals will not have experience in diagnosing EPTB. The fact that EPTB can present with a variety of symptoms that may mimic symptoms of other pathologies does pose a further challenge in diagnosis. In addition, obtaining an appropriate sample for confirmation of EPTB was frequently mentioned as a challenge. In summary, diagnosis of EPTB poses challenges due to the diversity of symptoms with which EPTB may present, the low level of suspicion of clinicians, and due to the difficulty in obtaining an adequate sample for confirmation.

Morphological markers for the detection of introgression from cultivated into wild carrot (Daucus carota L.) reveal dominant domestication traits.

Hybridisation and subsequent introgression have recently received much attention in the context of genetically modified crops. But crop-wild hybrid detection in the field can be difficult, as most domestication traits seem to be recessive, and the hybrid phenotype may also depend on the direction of the cross or environmental factors. Our aim was to develop a reliable set of morphological markers that differ between two wild and 13 cultivated carrots (Daucus carota L.) and to evaluate their inheritance in hybrid lines. We then examined these morphological markers in four F1 hybrids obtained by fertilising plants from the two wild accessions with pollen from two common carrot cultivars. Of the 16 traits that differed between the two carrot subspecies, three took intermediate values in the hybrids, eight resembled the cultivar parent (dominant domestication traits), two resembled the wild parent (domestication traits recessive), and three were not significant or growth condition-dependent. Root:shoot ratio was seven times higher for cultivars than for wild plants, while still attaining equivalent total dry weight, which shows that dry matter production by the shoot is much higher in cultivars than in wild plants. High root:shoot ratios were also present in the hybrids. While we found no maternal effects, the type of cultivar used for pollination had an impact on hybrid characteristics. The morphological markers developed here provide insights into the mode of inheritance of ecologically relevant traits and can be useful for pre-screening wild populations for hybrid detection prior to genetic analysis.

Protocolised inpatient care of diabetes mellitus.

BACKGROUND: The prevalence of hyperglycaemia in patients with diabetes mellitus at admission is high. Prevention and treatment is important to prevent further clinical complications. We have conducted a study evaluating implementation of a new protocol to standardise inpatient care of patients with diabetes mellitus. METHODS: A retrospective study including all glucose measurements of adult patients with diabetes mellitus type 1 o r 2 , admitted to a surgery department, was performed before and after implementation of the new protocol. This protocol included direct consultation of an internist and diabetes specialist nurse at admission, who initiated a daily treatment program and adjustment scheme based on glucose measurements four times a day by the HemoCue201DM glucose point of care device. We compared the prevalence of hyperglycaemia and hypoglycaemia before and after implementation with logistic regression analyses adjusted for age and gender. RESULTS: Overall, 360 patients with diabetes mellitus type 1 or 2 with 5322 glucose measurements were included. The risk of developing hyperglycaemia was significantly reduced after implementation of the protocol (22 patients with 65 hyperglycaemias) compared with before the intervention (70 patients with 417 hyperglycaemias) (RR adjusted 0.24 (95% confidence interval 0.19; 0.32)). Overall, 45 patients experienced 95 episodes of hypoglycaemia, which did not differ significantly between the two groups. CONCLUSION: After implementation of a new protocol to standardise inpatient care of diabetes mellitus we established a decrease in the risk to develop hyperglycaemia of 76% without an increased risk of developing hypoglycaemia. Implementation of this protocol required frequent glucose measurements which are facilitated by point of care glucose measurements.

Ab initio modeling of complex amorphous transition-metal-based ceramics.

Binary and ternary amorphous transition metal (TM) nitrides and oxides are of great interest because of their suitability for diverse applications ranging from high-temperature machining to the production of optical filters or electrochromic devices. However, understanding of bonding in, and electronic structure of, these materials represents a challenge mainly due to the d electrons in their valence band. In the present work, we report ab initio calculations of the structure and electronic structure of ZrSiN materials. We focus on the methodology needed for the interpretation and automatic analysis of the bonding structure, on the effect of the length of the calculation on the convergence of individual quantities of interest and on the electronic structure of materials. We show that the traditional form of the Wannier function center-based algorithm fails due to the presence of d electrons in the valence band. We propose a modified algorithm, which allows one to analyze bonding structure in TM-based systems. We observe an appearance of valence p states of TM atoms in the electronic spectra of such systems (not only ZrSiN but also NbO(x) and WAuO), and examine the importance of the p states for the character of the bonding as well as for facilitating the bonding analysis. The results show both the physical phenomena and the computational methodology valid for a wide range of TM-based ceramics.

Blood oxygenation level-dependent MRI of the skeletal muscle during ischemia in patients with peripheral arterial occlusive disease.

PURPOSE: To compare calf muscle Blood Oxygenation Level-Dependent (BOLD) response during ischemia in patients suffering from peripheral arterial occlusive disease (PAOD) and age-matched non-PAOD subjects. MATERIALS AND METHODS: PAOD patients with symptoms of intermittent calf claudication and an age-matched control group underwent T 2*-weighted single-shot multi-echo planar imaging on a whole-body MR scanner at 1.5 T. The muscle BOLD signal in the calf was acquired during 60 sec of baseline and 240 sec of ischemia induced by cuff compression. T 2* time courses in four calf muscles were evaluated. RESULTS: Significant differences in the mean T 2* values were noted after 150 sec of measurement (p < 0.05). Patients with PAOD revealed a significantly reduced BOLD signal decrease compared to an age-matched control group. CONCLUSION: Potential cause for this observation may be changes in the structure and/or the metabolic turnover of the muscle in PAOD patients.

[Solitary pulmonary nodule]. / Solitärer Lungenrundherd.

Primary pulmonary amyloidosis is rare. Three patterns of involvement have been described: tracheobronchial, nodular and diffuse parenchymal. The nodular parenchymal amyloid deposits are often multiple, much less common focal. We hereby present a case of a 70 year old patient, a former smoker, with coincidentally diagnosed solitary, pulmonary nodule, a rather common finding in CT. The list of differential diagnosis is long, as shown above, the amyloidosis is a quite uncommon cause, but it should be kept in mind.

Diagnostic pitfalls in postinterventional intraarterial magnetic resonance angiography after recanalization of femoropopliteal arterial occlusions.

BACKGROUND: Magnetic resonance (MR)-guided vascular interventions are of increasing interest, and, with the use of contrast-enhanced techniques, intraarterial contrast-enhanced MR angiography (ia-ce-MRA) competes with intraarterial digital subtraction angiography (ia-DSA) for the diagnostic evaluation of the infrainguinal vessel tree. PURPOSE: To assess the diagnostic value of ia-ce-MRA and high-resolution T1-weighted (hr-T1w) imaging compared to the gold-standard ia-DSA for residual stenosis and local dissections after femoropopliteal recanalization in patients with peripheral arterial occlusive disease (PAOD). MATERIAL AND METHODS: Eight patients with PAOD and short vessel occlusion of their femoropopliteal arteries underwent recanalization and balloon positioning under DSA. Patients were transferred to a short-bore MR scanner. Percutaneous transluminal angioplasty (PTA) was accomplished under MR fluoroscopy. Pre- and postinterventional ia-ce three-dimensional (3D) gradient-echo MRA with gadopentate dimeglumine was performed using the intraarterial introducer sheath. Maximum intensity projections (MIP) and multiplanar reconstructions (MPR) were calculated from the data set. High-resolution T1w images of the angioplasty region before and after dilatation were acquired. Control ia-DSA images were obtained. RESULTS: The postinterventional angioplasty results for stenosis grading were comparable in ia-MRA and ia-DSA. Only two of five local dissections in ia-DSA were visualized with the ia-ce-MRA runs including MIPs and MPRs. To clearly depict dissection, hr-T1w images were needed. CONCLUSION: Grading of stenotic lesions with ia-ce-MRA after PTA is comparable to ia-DSA. Intraarterial ce-MRA with calculated MIPs and MPRs is only partially sufficient to visualize local dissections after PTA. High-resolution T1w images are required for precise diagnosis of dissections in magnetic resonance tomography.

Hormone-inactive pituitary macroadenoma: an uncommon cause for the syndrome of inappropriate antidiuresis.

A 76-year-old patient was admitted with dizzy spells and fainting. Laboratory analysis indicated the syndrome of inappropriate antidiuresis, which was further characterized as type C ("reset osmostat"). Extended workup revealed a hormone - inactive pituitary macroadenoma. After complete transsphenoidal resection, serum sodium levels and plasma and urinary osmolality promptly normalized. Except for the gonadal axis, the anterior pituitary functions remained intact. There was no adenoma recurrence over a five-year follow-up, and repetitive testing on ad libitum fluid intake showed normal sodium concentrations. Thus, the pituitary macroadenoma represents the sole detectable cause for the syndrome of inappropriate antidiuresis in this patient.

[Gorlin-Goltz syndrome: manifestations in an elderly patient]. / Das Gorlin-Goltz-syndrom: Aspekte im Senium.

Gorlin-Goltz syndrome is a rare inherited genodermatosis with an autosomal dominant trait. We hereby present a case of a 69 year old patient with known Gorlin-Goltz syndrome to emphasize the peculiar syndrome manifestations in the elderly.