Description of interference in the measurement of troponin T by a high-sensitivity method

Introduction: Measurement of high-sensitivity troponin T (hs-TnT) has become an essential step in the diagnosis of acute myocardial infarction. This high-sensitivity method allows quantifying the concentration of troponin T in blood of healthy subjects with a lower inaccuracy compared to previous reagent generations. However, the presence of certain compounds in the sample may interfere with the result. We present a patient who had repeatedly high concentrations of hs-TnT in the serum sample that did not agreed with the signs and symptoms. In addition, ultrasensitive troponin I concentration was undetectable. Materials and methods: To investigate the presence of an interfering compound, different analysis were carried out. In order to discard macro complexes in the sample, the serum was precipitated with polyethylene glycol. In addition, the serum was incubated with Scantibodies Heterophilic Blocking Tube, which can block heterophilic antibodies. Finally, a size exclusion chromatography of the sample was performed by the manufacturer. What happened: The interfering substance was allocated into fractions with proteins of 150kDa, corresponding to high molecular weight proteins like immunoglobulin G (IgG). This compound was responsible for the falsely elevated hs-TnT results and it affected only the high-sensitivity methods. Main lesson: The detected interfering compound was probably an IgG. This type of interference must be kept in mind in front of discordant results, even if they are extremely rare. Therefore, interdisciplinary cooperation between clinicians, laboratory and manufacturer is essential

Glucagon stimulation test to assess growth hormone status in Prader-Willi syndrome

Growth hormone deficiency (GHD) must be confirmed before starting treatment in adults with Prader-Willi syndrome (PWS). Most studies use the growth-hormone-releasing hormone plus arginine (GHRH-arginine) test. No data are available on the glucagon stimulation test (GST) in PWS. We compared the utility of fixed-dose (1 mg) GST versus GHRH-arginine test in diagnosing GHD. Adults and late adolescents with PWS underwent both tests on separate days. In the GHRH-arginine test, GHD was defined according to body mass index. In the GST, two cutoffs were analyzed: peak GH concentration 90 kg). We analyzed 34 patients: 22 weighing ≤ 90 kg and 12 weighing > 90 kg. In patients weighing ≤ 90 kg, the two tests were concordant in 16 (72.72%) patients (k = 0.476, p = 0.009 with GST cutoff 90 kg, the two tests were not concordant with GST cutoff 90 kg, the < 1 ng/mL cutoff seems better. Larger studies are necessary to establish definitive glucagon doses and cutoffs, especially in extremely obese patients

Gamma heavy-chain disease accompanied with follicular lymphoma : a case report

Heavy chain diseases (HCD) are B-cell lymphoprolipherative disorders characterized by the production of monoclonal heavy chains without associated light chains. Some cases of gamma-HCD (γ-HCD) are concurrent with other lymphoid neoplasm. The monoclonal component is not always detectable by serum electrophoresis, and often an immunofixation procedure is necessary to detect this component. Prognosis is variable, and no established guidelines for follow-up are available. We describe a case of a challenging diagnosis of γ-HCD due to the absence of clinical signs frequently reported in the disease (anaemia and palatal oedema among others). Haematological malignancy was the first suspicion but bone marrow examination was negative. In addition, the presence of an autoimmune bicytopenia and a Klinefelter syndrome complicated the clinical context of the patient. A thoracoabdominal computed tomography reported many small adenopathies whose pathological and immunohystochemical study revealed a follicular lymphoma. Shortly after, serum inmunofixation secondary to an abnormal electrophoretic pattern revealed a gamma paraprotein without light chains. Eventually, γ-HCD in association with follicular lymphoma was the final diagnosis. This is the first case reporting this association

Impact of a Novel Strategy for Critical Values Communication for the Management of Patients Treated with Clozapine

Clozapine is an antipsychotic drug used to treat resistant schizophrenia and other disorders. Based on the actual Spanish legislation, patients treated with clozapine must undergo periodical haematological examinations and treatment should be reviewed when the haemogram shows either a leukocyte count of ≤ 3500/mm 3 or neutrophil count < 2000/mm 3. An automatic notification system has been developed to optimize patient management and it's utility was assessed following the implementation of the new system. When clozapine (CLO) laboratory test request was made, a reflex complete blood count test was also done. An automatic e-mail was sent by the laboratory information system to the physician when a CLO was ordered and low leukocyte or neutrophil counts were detected, or when a patient with an ordered CLO test did not attend the laboratory for blood drawing. For patients with haemogram alterations, the time to take clinical action was significantly decreased from 23 to 7 days (p = 0.02). Moreover, the adherence to Spanish Agency of Drugs and Sanitary Devices recommendations significantly increased from 45% to 76% (p = 0.02). For not attending patients, the days out of control decreased from 29 to 12 days, although it was not statistically significant (p = 0.06). This strategy has allowed the compliance of legal requirements, the improvement of patient safety, and the optimisation of clinical and laboratory procedure

Osteoporosis and Fragility Fractures in Patients with Liver Cirrhosis : Usefulness of FRAX® as a Screening Tool

This work was supported by the grant for initiation to research of the Societat Catalana de Digestologia 2015.Purpose: The purpose of this study is to assess the prevalence of osteoporosis and fragility fractures in patients with liver cirrhosis (LC) and determine the associated risk factors, evaluating the usefulness of FRAX as a screening method to identify patients at a higher risk of fracture. Methods: This was a cross-sectional study. Demographic, clinical, and analytical data were collected in a randomized sample of LC patients attending the Hepatology Department of a university hospital. We assessed the absolute risk of fracture at 10 years (FRAX) and based on the bone mineral density (BMD), the presence of morphometric vertebral fracture with a vertebral fracture assessment (VFA), or a thoracic and lumbar X-ray and bone microarchitecture with a trabecular bone score (TBS). Results: Ninety-two patients were included (71% male); the mean age was 63 ± 11.3 years. The main etiology of LC was alcoholism (52.2%), and most patients were Child-Pugh A (80.4%), with a mean model for end-stage liver disease (MELD) score of 10.1 ± 3.6. Sixteen patients (17.4%) had osteoporosis, and fifty-four (58.7%) had osteopenia. Eight patients (8.7%) had suffered at least one fragility fracture. The absolute risk of a major fracture according to FRAX without the BMD was 5.7 ± 4.5%. Risk factors associated with osteoporosis were age and the female sex. BM

FGF-23/vitamin D axis in type 1 diabetes: the potential role of mineral metabolism in arterial stiffness.

OBJECTIVE: To investigate the usefulness of Fibroblast Growth Factor 23 (FGF-23) and vitamin D as possible biomarkers of pre-clinical atherosclerosis, assessed as arterial stiffness (AS), in a group of subjects with type 1 diabetes (T1DM) and no previous cardiovascular events. RESEARCH DESIGN AND METHODS: 68 T1DM patients and 68 age- and sex-matched controls were evaluated for 1) age, sex, diabetes duration, physical activity, smoking, alcohol intake, BMI, blood pressure, fasting plasma glucose, HbA1c, estimated glomerular filtration rate (eGFR) and lipid profile; 2) microvascular complications; 3) blood concentrations of FGF-23 and mineral metabolism parameters (calcium, phosphate, parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25(OH)D)); 4) AS, assessed as aortic pulse wave velocity (aPWV); and 5) low-grade inflammation (hsCRP, IL-6, sTNFαR1, sTNFαR2) and endothelial dysfunction (ED) markers (ICAM-1, VCAM-1, E-Selectin). RESULTS: Patients with T1DM had higher aPWV compared with controls (p<0.001), but they did not present differences in 25(OH)D (70.3(50.4-86.2)nmol/L vs. 70.7(59.7-83.0)nmol/L; p = 0.462) and in FGF-23 plasma concentrations (70.1(38.4-151.9)RU/mL vs. 77.6(51.8-113.9)RU/mL; p = 0.329). In T1DM patients, higher concentrations of FGF-23 were positively associated with aPWV after adjusting for eGFR and classical cardiovascular risk factors (model 1: ß = 0.202, p = 0.026), other mineral metabolism parameters (model 2: ß = 0.214, p = 0.015), microvascular complications, low-grade inflammation and ED markers (model 3: ß = 0.170, p = 0.045). Lower 25(OH)D concentrations were also associated with higher aPWV after adjusting for all the above-mentioned factors (model 3: ß = -0.241, p = 0.015). CONCLUSIONS: We conclude that both FGF-23 plasma concentrations (positively) and 25(OH)D serum concentrations (negatively) are associated with AS in patients with T1DM and no previous cardiovascular events.Financial support was provided by a grant from the Fondo de Investigación Sanitaria (FIS) (PS09/01360 and PI12/00954) by Instituto de Salud Carlos III (Spain) and the Fundació La Marató de TV3-2008 (Project N° 081410). The study was also cofunded by Fondos FEDER and CIBER de Diabetes y Enfermedades Metabólicas asociadas CIBERDEM (CB07/08/0012), SAF2012-36186 and CP10/00438 to SF-V (Spanish Ministry of Economy and Competitiveness). CIBERDEM de Diabetes y Enfermedades Metabólicas asociadas (CB07708/ 0012) is an initiative of the Instituto de Salud Carlos III. GL was supported by a “Rio Hortega” research fellowship (CM12/00044) from the Instituto de Salud Carlos III (Spain). SF-V acknowledges support from the "Miguel Servet" tenure track program (CP10/ 00438), from the Fondo de Investigación Sanitaria (FIS), co-financed by the European Regional Development Fund (ERDF)

The poetic view of I. A. Bunin. On the basis of story analyses

V diplomové práci se zabýváme Hngvostylistickým rozborem povídkové tvorby Ivana Alexejeviče Bunina včetně kompozice s cílem dojít k určení principů jeho povídek, a tedy formulovat dimenzi básnicko-filozofickou. Příkladem takového rozboru může být např. analýza Buninovy básně z roku 1916 v závěru článku A. K. Žolkovského.! V této diplomové práci se konkrétně jedná o povídky IIepe6aJl (1892- 1898), 3UMHUU COH (1918), O oypaKe EMelle, KaKou 6blUlell 6cex yMHee (1921), B HeKomopOM l1apcm6e (1923), Cmapblu nopm (1927), IIep6a5l lllo606b (1930). Pro srovnání doplňujeme práci o kapitolu s ukázkou jiného, deníkového žánru, ve kterém se, stejně jako ve většině rozebíraných povídek, vyskytují hláskově instrumentované a rytmizované úseky, třebaže /(He6HuK (1917-1918) a OKa5lHHble OHU (1918-1919) nejsou díla čistě umělecká. V rámci analýzy provádíme rozbor fonetický, v němž zkoumáme, jak je využito vokálů a konsonantů, jejich distribuce k vyjádření významu a expresivity. Kromě hláskové instrumentace si všímáme rytmizace a jejího vztahu k sémantice textu. Důležitou se zde jeví rovněž pozornost zaměřená na sémanticko-Iexikální rovinu, tedy na sémantiku slov a jejich výběr, a na syntax. Na základě takového rozboru charakterizujeme autorovo básnické myšlení a podstatu toho, v čem tkví často zdůraňované mistrovství Buninova..

Salivary cortisol determination in ACTH stimulation test to diagnose adrenal insufficiency in patients with liver cirrhosis

Purpose. The prevalence of adrenal insufficiency (AI) in patients with decompensated liver cirrhosis is unknown. Because these patients have lower levels of cortisol-binding carrier proteins, their total serum cortisol (TSC) correlates poorly with free serum cortisol (FC). Salivary cortisol (SaC) correlates better with FC. We aimed to establish SaC thresholds for AI for the 250 μg intravenous ACTH test and to estimate the prevalence of AI in noncritically ill cirrhotic patients. Methods. We included 39 patients with decompensated cirrhosis, 39 patients with known AI, and 45 healthy volunteers. After subjects fasted ≥8 hours, serum and saliva samples were collected for determinations of TSC and SaC at baseline 0'(T) and at 30-minute intervals after intravenous administration of 250 μg ACTH [30'f(T), 60'f(T), and 90'(T)]. Results. Based on the findings in healthy subjects and patients with known AI, we defined AI in cirrhotic patients as SaC-T < 0.08 μg/dL (2.2 nmol/L), SaC-T60 < 1.43 μg/dL (39.5 nmol/L), or ΔSaC<1 μg/dL (27.6 nmol/L). We compared AI determination in cirrhotic patients with the ACTH test using these SaC thresholds versus established TSC thresholds (TSC-T < 9 μg/dL [248 nmol/L], TSC-T < 18 μg/dL [497 nmol/L], or ΔTSC<9 μg/dL [248 nmol/L]). SaC correlated well with TSC.The prevalence of AI in cirrhotic patients was higher when determined by TSC (48.7%) than by SaC (30.8%); however, this difference did not reach statistical significance. AI was associated with sex, cirrhosis etiology, and Child-Pugh classification. Conclusions. Measuring SaCwas more accurate than TSCin the ACTH stimulation test. Measuring TSC overestimated the prevalence of AI in noncritically ill cirrhotic patients