Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
PLoS One ; 14(12): e0226132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830073

RESUMO

BACKGROUND: Outcome of type 2 diabetes care depends on the acceptance of self-responsibility by informed patients, as treatment goals will otherwise be missed. AIMS AND METHODS: This pre/post-observational report describes the clinical outcome of type 2 diabetes care in patients with type 2 diabetes (N =930) admitted consecutively to a diabetes rehabilitation clinic (DRC) between June 2013, and June 2016, where they were exposed to standardized lifestyle modification with meals low in salt and rich in vegetables and fruits, totaling 1,200 to 1,600 kcal/d, and an add-on exercise load equivalent to 400-600 kcal/d. RESULTS: At admission, patients presented with multiple treatment modes, elevated HbA1c levels (7.6±1.5%, 60±16 mmol/mol), a high prevalence of co-morbidities dominated by obesity (79%), a low rate of influenza and pneumococcal immunization (<9%) and underuse of lipid-lowering drugs (-29%). Analysis of clinical and metabolic outcome after 3 weeks shows that simple standardization of and better adherence to treatment recommendations improved (p<0.0001) glucose (HbA1c -0.4±0.4%) and lipid metabolism (LDL/HDL ratio, -0.58±0.03), permitting a 39% reduction in insulin dosage, omission of insulin in 36/232 patients and omission of oral antidiabetic drugs (OADs) other than metformin and DPP4-inhibitors, while the use of GLP-1 analogs doubled to 5.2%. Improved outcome was independent of treatment strategy and more marked at initially high HbA1c at costs less than 25% of those encountered at a standard hospital. CONCLUSIONS: Our observations support the clinical notion that adherence to basic treatment recommendations is indispensable in type 2 diabetes care if metabolic and clinical treatment goals are to be met, and if inappropriate add-on over-medicalization with OADs and/or insulin is to be avoided. To this end, 'imprinting' patients at a DRC could be of considerable help.

2.
J Thromb Haemost ; 17(9): 1478-1488, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177606

RESUMO

BACKGROUND: In a large proportion of patients with a mild to moderate bleeding tendency no diagnosis can be established (bleeding of unknown cause, BUC). OBJECTIVES: To investigate possible dysfunctions in thrombin generation and plasma clot formation and lysis in patients with BUC from the Vienna Bleeding Biobank (VIBB). PATIENTS AND METHODS: Thrombin generation and plasma clot properties of 382 BUC patients were compared to those of 100 healthy controls and 16 patients with factor VIII (FVIII) activity ≤50%. RESULTS: Thrombin generation was significantly impaired in BUC patients compared to healthy controls, exhibiting a prolonged lag time and time to peak and decreased maximum thrombin generation, velocity index, and area under the curve (AUC). The assessment of clot formation and lysis in BUC patients revealed a lower clot formation rate (Vmax), resulting in a longer TTP, increased absorbance (ΔAbs), and a shorter clot lysis time (CLT) than in healthy controls. Comparing patients with FVIII activity ≤ 50% to those with BUC, parameters of thrombin generation and clot formation and lysis were either stronger or comparably impaired. Bleeding severity did not correlate with parameters of thrombin generation, clot formation, or clot lysis. CONCLUSION: Patients with BUC have an impaired hemostatic capacity reflected by a lower thrombin-generation potential, a lower clot formation rate, increased clot turbidity, and shorter clot lysis time, which might contribute to their increased bleeding tendency. Assays monitoring these parameters can alert physicians of hemostatic impairment and should be considered in situations where traditional hemostatic lab tests fail to reveal the clinical bleeding tendency.

4.
United European Gastroenterol J ; 7(5): 651-661, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31210943

RESUMO

Background: Spontaneous bacterial peritonitis (SBP) is defined as an ascitic polymorphonuclear cell count (A-PMN) > 250 cells/µl. Objective: We aimed to investigate the prognostic value of ascitic fluid cell counts in patients without SBP. Patients and methods: A total of 178 patients were included and stratified by ascitic cell counts at index paracentesis: A-LEUK-low (<250/µl), A-LEUK-intermediate (250-500/µl) and A-LEUK-SBP (>500/µl) for leukocytes; A-PMN-low (<125/µl), A-PMN-intermediate (125-250/µl) and A-PMN-SBP (>250/µl) for PMN cells. Results: One-year mortality was comparable between group A-LEUK-SBP (53.9%) and patients with subclinical cell counts (34.5% for A-LEUK-low, 43.5% for A-LEUK-intermediate, log-rank p = 0.547). However, we observed an increase in one-year mortality already in group A-PMN-intermediate with 75% and A-PMN-SBP with 80.9% (vs 40.5% for A-PMN-low, log-rank p = 0.016).Importantly, increases of A-PMN cell counts between two paracenteses were associated with increased mortality: per 100 cells/µl increase of absolute A-PMN cell count: hazard ratio (HR): 1.03 (95% confidence interval (CI): 1.01-1.06), p = 0.005; per 5% increase of relative PMN cell count: HR: 1.15 (95% CI: 1.06-1.26), p = 0.001. Conclusion: Patients with PMN cell counts of 125-250/µl are at high risk for mortality, which was very similar to SBP patients with PMN cell counts >250/µl. This highlights the need for preventive strategies. The prognostic value of changes in relative ascitic PMN cell counts should be evaluated in future studies.

5.
Diabetes Metab Syndr Obes ; 12: 813-820, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31213867

RESUMO

Purpose: To explore differences in baseline characteristics following three weeks of semi-standardized in-patient care between patients with obesity without and with type 2 diabetes (T2D). Patients and methods: Patients without or with T2D were matched according to age, sex, and BMI. Food intake was restricted to 1,200-1,600 kcal/d to which a 400-600 kcal/d exercise load was added, and data were compared using Student's t-test, general linear models, and Spearman-rank correlations. Results: At baseline, patients with obesity and T2D displayed, besides elevated blood glucose and HbA1c values, higher serum liver enzymes (p<0.001-0.05), triglycerides, and CRP (p<0.01) and a greater prevalence of treated hyperlipidemia (p<0.001) than those with plain obesity who showed only higher LDL and HDL cholesterol levels (+9.0% and +16.0%). In response to three-weeks of standardized life-style change, both groups improved their vital variables and risk scores (p<0.001). While improvement in cholesterol slightly favored patients with plain obesity, the need for anti-hyperlipidemics (+25%) rose in both groups, albeit that for anti-hypertensives (+50%) increased only in patients with obesity and add-on T2D. Conclusion: Moderate changes in lifestyle improve the clinical condition, including coronary heart disease and premature mortality risk scores (HARD-CHD and ABSI) in patients with obesity both in the absence and presence of T2D, with the latter seemingly increasing the risk of hepatic steatosis and systemic inflammation.

6.
J Clin Med ; 8(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010216

RESUMO

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a life-threatening condition clinically presenting as SIRS (Systemic Inflammatory Response Syndrome). However, there is no comprehensive data concerning diagnostic algorithms, prevalence, outcome and biomarker performance in SIRS patients. We conducted a prospective observational cohort study on 451 consecutive patients fulfilling ≥2 SIRS criteria. The Hscore and the HLH-2004 criteria were used to determine the presence of sHLH, and the correlation of the screening-biomarkers ferritin, sCD25, and sCD163 with both scores was assessed. Out of 451 standard-care SIRS patients, five patients had high Hscores (≥169), suggesting incipient or HLH-like disease, and these patients were in urgent need for intensified therapy. However, none of these patients fulfilled five HLH-2004 criteria required for formal diagnosis. From the studied biomarkers, ferritin correlated strongest to both the HLH-2004 criteria and the Hscore (rs = 0.72, 0.41, respectively), and was the best predictor of 30-day survival (HR:1.012 per 100 µg/L, 95% CI: 1.004-1.021), when adjusted for patient's age, sex, bacteremia and malignant underlying-disease. Also, the HLH-2004 (HR per point increase: 1.435, 95% CI: 1.1012-2.086) and the Hscore (HR per point increase:1.011, 95% CI: 1.002-1.020) were independent predictors of 30-day-survival. The Hscore detected patients in hyperinflammatory states requiring urgent therapy escalation. Degrees of hyperinflammation, as assessed by ferritin and both HLH scores, are associated with worse outcomes.

7.
J Infect Dis ; 219(12): 1934-1939, 2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-30668796

RESUMO

BACKGROUND: Drug-induced immunosuppression in kidney transplant recipients is crucial to prevent allograft rejection, but increases risk for infectious disease. Immunologic monitoring to tailor immunosuppressive drugs might prevent alloreactivity and adverse effects simultaneously. The apathogenic torque teno virus (TTV) reflects the immunocompetence of its host and might act as a potential candidate for a holistic monitoring. METHODS: We screened all 1010 consecutive patients from the prospective Vienna Kidney Transplant Cohort Study for availability of allograft biopsies and adequately stored sera for TTV quantification by polymerase chain reaction. RESULTS: Patients with acute biopsy-proven alloreactivity according to the Banff classification (n = 33) showed lower levels of TTV in the peripheral blood compared to patients without rejection (n = 80) at a median of 43 days before the biopsy. The risk for alloreactivity decreased by 10% per log level of TTV copies/mL (risk ratio, .90 [95% confidence interval, .84-.97]; P = .005). TTV levels >1 × 106 copies/mL exclude rejection with a sensitivity of 94%. Multivariable generalized linear modeling suggests an independent association between TTV level and alloreactivity. CONCLUSIONS: TTV is a prospective biomarker for risk stratification of acute biopsy-proven alloreactivity in kidney transplant recipients and might be a potential tool to tailor immunosuppressive drug therapy.


Assuntos
Infecções por Vírus de DNA/etiologia , Imunossupressão/efeitos adversos , Transplante de Rim/efeitos adversos , Torque teno virus/patogenicidade , Adulto , Idoso , Biópsia , Infecções por Vírus de DNA/virologia , DNA Viral/genética , Feminino , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/virologia , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Risco , Medição de Risco , Carga Viral/métodos
8.
J Nucl Med ; 60(4): 486-491, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30237210

RESUMO

The adenosine triphosphate-binding cassette transporters P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are 2 efflux transporters at the blood-brain barrier (BBB) that effectively restrict brain distribution of dual ABCB1/ABCG2 substrate drugs, such as tyrosine kinase inhibitors. Pharmacologic inhibition of ABCB1/ABCG2 may improve the efficacy of dual-substrate drugs for treatment of brain tumors, but no marketed ABCB1/ABCG2 inhibitors are currently available. In the present study, we examined the potential of supratherapeutic-dose oral erlotinib to inhibit ABCB1/ABCG2 activity at the human BBB. Methods: Healthy men underwent 2 consecutive PET scans with 11C-erlotinib: a baseline scan and a second scan either with concurrent intravenous infusion of the ABCB1 inhibitor tariquidar (3.75 mg/min, n = 5) or after oral intake of single ascending doses of erlotinib (300 mg, n = 7; 650 mg, n = 8; or 1,000 mg, n = 2). Results: Although tariquidar administration had no effect on 11C-erlotinib brain distribution, oral erlotinib led, at the 650-mg dose, to significant increases in volume of distribution (23% ± 13%, P = 0.008), influx rate constant of radioactivity from plasma into brain (58% ± 26%, P = 0.008), and area under the brain time-activity curve (78% ± 17%, P = 0.008), presumably because of combined partial saturation of ABCG2 and ABCB1 activity. Inclusion of further subjects into the 1,000-mg dose group was precluded by adverse skin events (rash). Conclusion: Supratherapeutic-dose erlotinib may be used to enhance brain delivery of ABCB1/ABCG2 substrate anticancer drugs, but its clinical applicability for continuous ABCB1/ABCG2 inhibition at the BBB may be limited by safety concerns.

9.
Biopreserv Biobank ; 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30335475

RESUMO

BACKGROUND AND AIM: It is increasingly recognized that biomedical research has serious reproducibility issues, which could be overcome at least in part by standardized processing of biomaterials. Therefore, professional biobanks have emerged, positively influencing sample and data quality. However, quantitative data about a biobank's contribution to published results are still hard to find, although they could serve as valuable benchmark figures for the community. We therefore aimed to report usage data from the MedUni Wien Biobank facility regarding its prospective fluid cohorts. METHODS: Input and access statistics and publication output were reported for the years 2010-2017. Performance dynamics were tested by correlation analyses according to Spearman. Additionally, virtual costs per sample were calculated. RESULTS: The amount of annually collected aliquots rose significantly from 68,500 in 2010 to 151,966 in 2017 (p = 0.015), although no further increase was recorded after 2012 (p = 0.266). In the same period, the quotient of requested to stored aliquots increased from 3.5% to 6.1% (p = 0.001), as the yearly number of requested aliquots nearly quadrupled from 2401 to 9342. Likewise, the number of published research articles per year to which the MedUni Wien Biobank contributed increased from 2 (total impact factor: 8.6) in 2010 to 16 (total impact factor: 69.0) in 2017, resulting in a total of 69 identified publications. Currently, the biobank operates at 15- to 20-fold overproduction, leading to virtual costs per accessed sample of ∼€20. CONCLUSION: The reported usage data might serve as a benchmark for other hospital-integrated biobanks, and implies that academic biobanks are able to produce considerable scientific impact at comparable moderate costs.

10.
Sci Rep ; 8(1): 12742, 2018 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-30143672

RESUMO

Disseminated intravascular coagulation (DIC) is a life-threatening event that is the endpoint of a pathologically activated cascade leading to excessive consumption of platelets culminating in bleeding. Several diseases are known to be associated with DIC, some of which may also occur during pregnancy or the puerperium. One of the potential risk factors that have been considered as a potential trigger for DIC is the retention of a highly macerated fetus after intrauterine fetal death (IUFD). However, sparse evidence exists on its clinical implication on hemostasis parameters. In this retrospective single-center study, we investigated the role of fetal maceration grades 0-III on the risk of DIC in 91 women following IUFD between gestational weeks (+days) 22 + 0 and 41 + 6 between 2003 and 2017. We calculated the Erez DIC-score after consideration of maternal platelet count (PC), prothrombin time (PT) and fibrinogen (Fib) and correlated the findings with fetal maceration grade. Mean (±SD) age of women was 32.1 ± 6.7 years. Neither maternal hemostasis parameters (PC, PT, Fib), nor the Erez score showed a statistically significant difference between maceration grades 0-III with median values of 1 for all four grades (maceration grade I: range 0 to 27; I: 0 to 51; II: 0 to 52; III: 0 to 39). We therefore conclude, that the pathophysiology of DIC in women after singleton IUFD is unrelated to the degree of fetal maceration.


Assuntos
Coagulação Intravascular Disseminada/etiologia , Morte Fetal , Feto/patologia , Adolescente , Adulto , Coagulação Intravascular Disseminada/sangue , Feminino , Fibrinogênio , Hemorragia/etiologia , Hemostasia , Humanos , Pessoa de Meia-Idade , Contagem de Plaquetas , Gravidez , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
11.
Sci Rep ; 8(1): 12233, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-30111827

RESUMO

Bacteraemia is a life-threating condition requiring immediate diagnostic and therapeutic actions. Blood culture (BC) analyses often result in a low true positive result rate, indicating its improper usage. A predictive model might assist clinicians in deciding for whom to conduct or to avoid BC analysis in patients having a relevant bacteraemia risk. Predictive models were established by using linear and non-linear machine learning methods. To obtain proper data, a unique data set was collected prior to model estimation in a prospective cohort study, screening 3,370 standard care patients with suspected bacteraemia. Data from 466 patients fulfilling two or more systemic inflammatory response syndrome criteria (bacteraemia rate: 28.8%) were finally used. A 29 parameter panel of clinical data, cytokine expression levels and standard laboratory markers was used for model training. Model tuning was performed in a ten-fold cross validation and tuned models were validated in a test set (80:20 random split). The random forest strategy presented the best result in the test set validation (ROC-AUC: 0.729, 95%CI: 0.679-0.779). However, procalcitonin (PCT), as the best individual variable, yielded a similar ROC-AUC (0.729, 95%CI: 0.679-0.779). Thus, machine learning methods failed to improve the moderate diagnostic accuracy of PCT.


Assuntos
Bacteriemia/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/complicações , Adulto , Idoso , Área Sob a Curva , Bacteriemia/sangue , Bacteriemia/classificação , Biomarcadores/sangue , Calcitonina/sangue , Estudos de Coortes , Feminino , Previsões , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Estudos Prospectivos , Precursores de Proteínas/sangue , Curva ROC , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/microbiologia
12.
Sci Rep ; 8(1): 9151, 2018 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-29904183

RESUMO

Burnout and work-related stress symptoms of anxiety disorder and depression cause prolonged work absenteeism and early retirement. Hence, reliable identification of patients under risk and monitoring of treatment success is highly warranted. We aimed to evaluate stress-specific biomarkers in a population-based, "real-world" cohort (burnouts: n = 40, healthy controls: n = 26), recruited at a preventive care ward, at baseline and after a four-month follow up, during which patients received medical and psychological treatment. At baseline, significantly higher levels of salivary cortisol were observed in the burnout group compared to the control group. This was even more pronounced in midday- (p < 0.001) and nadir samples (p < 0.001) than for total morning cortisol secretion (p < 0.01). The treatment program resulted in a significant reduction of stress, anxiety, and depression scores (all p < 0.001), with 60% of patients showing a clinically relevant improvement. This was accompanied by a ~30% drop in midday cortisol levels (p < 0.001), as well as a ~25% decrease in cortisol nadir (p < 0.05), although not directly correlating with score declines. Our data emphasize the potential usefulness of midday and nadir salivary cortisol as markers in the assessment and biomonitoring of burnout.


Assuntos
Esgotamento Psicológico/metabolismo , Ritmo Circadiano , Hidrocortisona/metabolismo , Saliva/metabolismo , Vigília , Adulto , Biomarcadores/metabolismo , Esgotamento Psicológico/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Front Psychiatry ; 9: 165, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29755375

RESUMO

Background: Previous studies have shown that the hypothalamus-pituitary-adrenal-axis (HPA-axis) is closely involved in the development of affective disorders. Given that early life events are also linked to dysregulation of the same system, there might be an association between childhood adversities and suicidal behavior in affective disorders, moderated by HPA-axis genes. We aimed to investigate a potential association between childhood trauma and previous suicide attempts in affective disorder patients, moderated by variants of the corticotropin-releasing hormone receptor 1 (CRHR1) gene. Methods: The current pilot study is part of an ongoing study on suicidal behavior in affective disorders (VieSAD). Two hundred fifty eight Caucasian affective disorder patients were assessed at the Department of Psychiatry and Psychotherapy of the Medical University Vienna and the Karl Landsteiner University for Health and Science. An assemblage of psychiatric interviews was performed (e.g., SCAN, HAMD, SBQ-R, CTQ) and DNA samples of peripheral blood cells were genotyped with TaqMan® SNP Genotyping Assays (rs7209436, rs4792887, rs110402, rs242924, and rs242939). Results: Neither genetic, nor haplotypic associations between CRHR1 polymorphisms and previous suicide attempts could be established for the present sample. Using a binary logistic regression model, significant gene-environment-interactions were found for the single nucleotide polymorphisms (SNPs) rs7209436 and rs110402, reflecting the impact of childhood trauma and CRHR1 polymorphisms on previous suicide attempts. Limitations: A larger sample size will be required to ultimately elucidate the link between childhood trauma and the HPA axis in suicidal behavior. Conclusion: This pilot study presents promising gene-environment-interaction findings in affective disorder patients with a history of suicide attempts.

14.
Front Immunol ; 9: 876, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29740454

RESUMO

Anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are the most commonly used diagnostic markers of rheumatoid arthritis (RA). These antibodies are predominantly of the immunoglobulin (Ig) M (RF) or IgG (ACPA) isotype. Other subtypes of both antibodies-particularly IgA isotypes and other autoantibodies-such as RA33 antibodies-have been repeatedly reported but their diagnostic value has still not been fully elucidated. Here, we investigated the prevalence of IgA, IgG, and IgM subtypes of RF, ACPA, and RA33 antibodies in patients with RA. To determine the diagnostic specificity and sensitivity sera from 290 RA patients (165 early and 125 established disease), 261 disease controls and 100 healthy subjects were tested for the presence of IgA, IgG, and IgM isotypes of RF, ACPA, and RA33 by EliA™ platform (Phadia AB, Uppsala, Sweden). The most specific antibodies were IgG-ACPA, IgA-ACPA, and IgG-RF showing specificities >98%, closely followed by IgG- and IgA-RA33 while IgM subtypes were somewhat less specific, ranging from 95.8% (RA33) to 90% (RF). On the other hand, IgM-RF was the most sensitive subtype (65%) followed by IgG-ACPA (59.5%) and IgA-RF (50.7%). Other subtypes were less sensitive ranging from 35 (IgA-ACPA) to 6% (IgA-RA33). RA33 antibodies as well as IgA-RF and IgA-ACPA were found to increase the diagnostic sensitivity of serological testing since they were detected also in seronegative patients reducing their number from 109 to 85. Moreover, analyzing IgM-RF by EliA™ proved more sensitive than measuring RF by nephelometry and further reduced the number of seronegative patients to 76 individuals. Importantly, among antibody positive individuals, RA patients were found having significantly more antibodies (≥3) than disease controls which generally showed one or two antibody species. Thus, increasing the number of autoantibodies in serological routine testing provides valuable additional information allowing to better distinguish between RA and other rheumatic disorders, also in patients not showing antibodies in current routine diagnostics. In conclusion, testing for multiple autoantibody specificities increases the diagnostic power of autoimmune diagnostics and could further support physicians in clinical decision-making.


Assuntos
Anticorpos Anti-Proteína Citrulinada/sangue , Artrite Reumatoide/diagnóstico , Isotipos de Imunoglobulinas/sangue , Fator Reumatoide/sangue , Testes Sorológicos/métodos , Idoso , Anticorpos Anti-Proteína Citrulinada/imunologia , Especificidade de Anticorpos/imunologia , Artrite Reumatoide/sangue , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Testes Diagnósticos de Rotina/métodos , Feminino , Voluntários Saudáveis , Humanos , Isotipos de Imunoglobulinas/imunologia , Masculino , Pessoa de Meia-Idade , Fator Reumatoide/imunologia , Sensibilidade e Especificidade
15.
Arch Pathol Lab Med ; 142(8): 992-997, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29624078

RESUMO

CONTEXT: - Coagulation testing is challenging and depends on preanalytic factors, including the citrate buffer concentration used. OBJECTIVE: - To better estimate preanalytic effects of the citrate buffer concentration in use, the difference between results obtained by samples with 3.2% and 3.8% citrate was evaluated. DESIGN: - In a prospective observational study with 76 volunteers, differences related to the citrate concentration were evaluated. For both buffer concentrations, reference range intervals were established according to the recommendations of the C28-A3 guideline published by the Clinical and Laboratory Standards Institute. RESULTS: - In our reagent-analyzer settings, most parameters evaluated presented good comparability between citrated samples taken with 3.2% and 3.8% trisodium buffer. The ellagic acid containing activated partial thromboplastin time reagent (aPTT-FS) indicated a systemic and proportional difference between both buffer concentrations, leading to an alteration in its reference ranges. Further, a confirmation test for lupus anticoagulant assessment (Staclot LA) showed only a moderate correlation ( rρ = 0.511) with a proportional deviation between both citrate concentrations. Further, a statistically significant difference was found in the diluted Russell viper venom time confirmation testing, coagulation factors V and VIII, and the protein C activity, which was found to be of minor clinical relevance. CONCLUSIONS: - With caution regarding the potential impact of the reagent-analyzer combination, our findings demonstrate the comparability of data assessed with 3.2% and 3.8% buffered citrated plasma. As an exception, the aPTT-FS and the Staclot LA assay were considerably affected by the citrate concentration used. Further studies are required to confirm our finding using different reagent-analyzer combinations.


Assuntos
Testes de Coagulação Sanguínea/métodos , Citrato de Sódio , Tampões (Química) , Voluntários Saudáveis , Humanos , Estudos Prospectivos , Valores de Referência
16.
PLoS One ; 13(3): e0194135, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29529063

RESUMO

BACKGROUND: T1D treatment requires informed self-responsible patients, who, however, frequently miss their therapeutic goals, providing considerable potential for improvement. METHODS: This observational report evaluates T1D patients [N = 109], aged ≥18 years (range 22-82), poorly controlled at home, at and 3 weeks after their admission to our diabetes rehabilitation clinic [DRC], where they were offered standardized, but unmonitored life-style modification. RESULTS: At admission, patients displayed elevated HbA1c values (66 mmol/mol [57; 81]), a high prevalence of co-morbidities (88%), lipodystrophies due to monolocal insulin injections (42%), a low rate of influenza (16%) and pneumococcal (7%) immunization, and underuse of lipid-lowering drugs (-38%). Standardization of life-style improved glucose (p<0.0001) and lipid metabolism (LDL/HDL ratio p<0.01) permitting reduction of insulin dose and reduction of add-on glucose-lowering drugs (GLDs) other than metformin. Outcome was independent of the mode of insulin treatment strategy and more marked at initially high HbA1c, with DRC-costs/d less than 25% of those encountered at standard hospitals. CONCLUSION: Type 1 diabetes care requires i) insulin treatment, food intake and life style to be handled in concert, ii) this need cannot be replaced by arbitrary addition of add-on GLDs, and iii) training to this end is 75% cheaper at a DRC than in standard hospitals.


Assuntos
Diabetes Mellitus Tipo 1/reabilitação , Adulto , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Estilo de Vida , Metabolismo dos Lipídeos , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade
17.
Sci Rep ; 8(1): 692, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29330410

RESUMO

The inconsistent findings on the association between COMT (catecholamine-O-methyl-transferase) and suicidal behaviour gave reason to choose a clear phenotype description of suicidal behaviour and take childhood maltreatment as environmental factor into account. The aim of this candidate-gene-association study was to eliminate heterogeneity within the sample by only recruiting affective disorder patients and find associations between COMT polymorphisms and defined suicidal phenotypes. In a sample of 258 affective disorder patients a detailed clinical assessment (e.g. CTQ, SCAN, HAMD, SBQ-R, VI-SURIAS, LPC) was performed. DNA of peripheral blood samples was genotyped using TaqMan® SNP Genotyping Assays. We observed that the haplotype GAT of rs737865, rs6269, rs4633 is significantly associated with suicide attempt (p = 0.003 [pcorr = 0.021]), and that there is a tendency towards self-harming behaviour (p = 0.02 [pcorr = 0.08]) and also NSSI (p = 0.03 [pcorr = 0.08]), though the p values did not resist multiple testing correction. The same effect we observed with the 4-marker slide window haplotype, GATA of rs737865, rs6269, rs4633, rs4680 (p = 0.009 [pcorr = 0.045]). The findings support an association between the COMT gene and suicidal behaviour phenotypes with and without childhood maltreatment as environmental factor.


Assuntos
Catecol O-Metiltransferase/genética , Transtornos do Humor/patologia , Tentativa de Suicídio , Adolescente , Adulto , Idoso , Genótipo , Haplótipos , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Transtornos do Humor/genética , Transtornos do Humor/terapia , Fenótipo , Polimorfismo de Nucleotídeo Único , Medição de Risco , Adulto Jovem
18.
J Am Soc Nephrol ; 29(2): 591-605, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29242250

RESUMO

Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)-positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, -4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.


Assuntos
Bortezomib/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/fisiopatologia , Antígenos HLA/imunologia , Transplante de Rim , Inibidores de Proteassoma/uso terapêutico , Adulto , Aloenxertos/imunologia , Anticorpos/sangue , Bortezomib/efeitos adversos , Progressão da Doença , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/complicações , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores de Proteassoma/efeitos adversos , Proteinúria/etiologia , Fatores de Tempo , Falha de Tratamento
19.
Biochem Med (Zagreb) ; 27(3): 030705, 2017 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-28900368

RESUMO

INTRODUCTION: Lupus anticoagulant (LAC) testing is challenging. Most data are derived from a well-controlled study environment with potential alterations to daily routines. The aim of this retrospective cohort study was to assess the capacity of various LAC screening tests and derived mixing tests to predict a positive result in subsequent confirmation tests in a large cohort of patients. MATERIALS AND METHODS: In 5832 individuals, we retrospectively evaluated the accuracy of the aPTT-A, aPTT-LAscreen, aPTT-FS and dRVVTscreen and of their derived mixing tests in detecting a positive confirmation test result within the same blood specimen. The group differences, degree of correlation and the predictive accuracy of LAC coagulation tests were analysed using the Mann-Whitney U test, the Spearman-rank-correlation and by area under the receiver operating characteristic curve (ROC-AUC) analysis. ROC-AUCs were compared with the Venkatraman´s permutation test. RESULTS: The pre-test probability of patients with clinically suspected LAC was 36% in patients without factor deficiency or anticoagulation therapy. The aPTT-LAscreen showed the best diagnostic accuracy with a ROC-AUC of 0.84 (95% CI: 0.82 - 0.86). No clear advantage of the dRVVT-derived mixing test was detectable when compared to the dRVVTscreen (P = 0.829). Usage of the index of circulating anticoagulant (ICA) did not improve the diagnostic power of respective mixing tests. CONCLUSIONS: Among the parameters evaluated, aPTT-LAscreen and derived mixing test parameters were the most accurate tests. In our study cohort, neither other mixing test nor the ICA presented any further advantage in LAC diagnostics.


Assuntos
Anticoagulantes/sangue , Anticoagulantes/metabolismo , Inibidor de Coagulação do Lúpus/sangue , Inibidor de Coagulação do Lúpus/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Coagulação Sanguínea/fisiologia , Feminino , Testes Hematológicos/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Adulto Jovem
20.
PLoS One ; 12(5): e0177174, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28475643

RESUMO

Endurance sports are enjoying greater popularity, particularly among new target groups such as the elderly. Predictors of future physical capacities providing a basis for training adaptations are in high demand. We therefore aimed to estimate the future physical performance of elderly marathoners (runners/bicyclists) using a set of easily accessible standard laboratory parameters. To this end, 47 elderly marathon athletes underwent physical examinations including bicycle ergometry and a blood draw at baseline and after a three-year follow-up period. In order to compile a statistical model containing baseline laboratory results allowing prediction of follow-up ergometry performance, the cohort was subgrouped into a model training (n = 25) and a test sample (n = 22). The model containing significant predictors in univariate analysis (alanine aminotransferase, urea, folic acid, myeloperoxidase and total cholesterol) presented with high statistical significance and excellent goodness of fit (R2 = 0.789, ROC-AUC = 0.951±0.050) in the model training sample and was validated in the test sample (ROC-AUC = 0.786±0.098). Our results suggest that standard laboratory parameters could be particularly useful for predicting future physical capacity in elderly marathoners. It hence merits further research whether these conclusions can be translated to other disciplines or age groups.


Assuntos
Alanina Transaminase/sangue , Atletas , Colesterol/sangue , Ácido Fólico/sangue , Peroxidase/sangue , Aptidão Física/fisiologia , Ureia/sangue , Idoso , Ciclismo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resistência Física/fisiologia , Estudos Prospectivos , Corrida/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA