A practical approach example to measurement uncertainty: Evaluation of 26 immunoassay parameters.

Introduction: Measurement uncertainty is a non-negative parameter that characterizes the distribution of all values appropriate to the measured size and is associated with the measured result. In this study, we aimed to compare the results with various suggestions and produce more qualified results by calculating the measurement uncertainties of the immunoassays like fertility hormones, drug concentration tests, cardiac markers, thyroid function tests and tumour markers. Materials and methods: Uncertainty calculation was made in accordance with the top-down approach according to Nordtest guide. The 12-month study of internal and external quality assessment results were used. The parameters of drug concentration tests were performed on the Abbott Architect c8000, other hormones/markers on the i2000 of the same brand. Results: Factors that increased the measurement uncertainty of a test were due to external quality control data. The calculations showed that 13 of 26 parameters satisfied quality requirements. The highest uncertainty value, with 28% belonged to cancer antigen 19-9 test. The lowest value was calculated for prolactin with 8.3%. Dehydroepiandrosterone sulfate and phenytoin performed poorly in terms of measurement uncertainty, although internal and external quality control assessment results were considered favourable for both. Conclusion: It is recommended that the concept of measurement uncertainty, which plays an important role in the total quality performance of the laboratory, should be followed up by the clinical laboratory experts at certain time intervals and should be increased the awareness of clinicians about the subject.

Otolin-1, as a Potential Marker for Inner Ear Trauma after Mastoidectomy.

OBJECTIVES: The aim of this prospective clinical study was to examine the negative effect of drilling by measuring peripheral Otolin-1 levels as a potential biomarker. MATERIALS AND METHODS: Patients who underwent mastoidectomy due to chronic otitis media were included in the study. Otolin-1 levels were measured preoperatively and 6 h postoperatively, and total drilling time was noted. Preoperative serum Otolin-1 levels in 31 patients were compared with those in31 age- and sex-matched healthy individuals. Pre- and postoperative serum Otolin-1 levels were also compared. RESULTS: Tympanoplasty was performed through canal wall-down (n=17) and wall-up mastoidectomy (n=14) in our sample. The mean duration of drilling was 52.7±13.8min. Preoperative serum Otolin-1 levels were significantly lower in patients than in healthy controls (21.0±3.0 vs. 23.5±3.9 pg/mL, p=0.006). We also found significantly higher postoperative serum Otolin-1 levels than preoperative levels (21.0±3.0 vs. 27.0±6.9 pg/mL, p<0.001). An increase in serum Otolin-1 levels during surgery was independently associated with drilling time in multivariate linear regression analysis (r=0.309, p<0.001). CONCLUSION: A nearly postoperative increase in serum Otolin-1 levels after mastoidectomy was independently associated with drilling time. We show that serum Otolin-1 levels may be used to indicate inner ear trauma in clinical practice in the future.

Prognostic value of serum pregnancy-associated plasma protein A level at the initial ED presentation in elderly patients with CAP.

OBJECTIVE: This study aims to compare serum pregnancy-associated plasma protein A (PAPP-A) levels in surviving and nonsurviving elderly patients with community-acquired pneumonia (CAP), investigating whether PAPP-A is correlated with CAP prediction scores and whether PAPP-A can successfully predict 28-day mortality rates in elderly patients. METHODS: This prospective, observational, single-center, cross-sectional study was conducted at the emergency department (ED) of Celal Bayar University Hospital in Manisa, Turkey, between January and September 2014. All patients underwent follow-up evaluations 28 days after admission. The end point was defined as all-cause mortality. RESULTS: A total of 100 elderly patients (mean age, 77.3 ± 7.6 years [range, 65-94 years]); 60% men) with CAP were enrolled in this study. All-cause mortality at the 28-day follow-up evaluation was 22%. Admission PAPP-A levels were significantly higher in nonsurvivors compared with 28-day survivors (10.3 ± 4.5 vs 3.8 ± 2.6 ng/mL, P < .001). A significant and positive correlation between admission PAPP-A levels and pneumonia severity index; confusion, oxygen saturation, respiratory rate, blood pressure, and age 75 years or older; and confusion, urea, respiratory rate, blood pressure, and age older than 65 years scores was found (r = .440, P < .001; r = .395, P < .001; and r = .359, P < .001, respectively). Moreover, we determined that the optimal PAPP-A cutoff for predicting 28-day mortality at the time of ED admission was 5.1 ng/mL, with 77.3% sensitivity and 77.9% specificity. CONCLUSIONS: Serum PAPP-A level is valuable for predicting mortality and the severity of the disease among elderly patients with CAP at ED admission. Thus, PAPP-A might play a further role in the clinical assessment of the severity of CAP.

De novo produced anti-human leukocyte antigen antibodies relation to alloimmunity in patients with chronic renal failure.

AIMS: Chronic renal failure causes patients to become dialysis dependent, which is exhausting for them both financially and psychologically. However, the definitive treatment of chronic renal failure is transplantation. One of the crucial factors affecting success in transplantation is the presence of anti-human leukocyte antigen (HLA) antibodies in patients. HLA alloimmunization is caused by various sensitization events such as blood transfusion, pregnancy, and transplantation. In this study, different sensitization events were compared to determine the effectiveness on the panel-reactive antibody status in female solid organ transplantation candidates based upon pregnancy. RESULTS: When results were evaluated in terms of alloimmunization rates, 62.8%, 73.4%, and 14.9% of the patients were found to have blood transfusion, pregnancy, and rejection history, respectively. Three hundred twenty-six of the 444 women had had at least one pregnancy. Panel-reactive antibody (PRA) (class I and/or II)-positive rates were significantly higher among patients with pregnancy and blood transfusion history (43.7%) than patients with only pregnancy history (27.5%) and pregnancy and transplantation history (40%). While transplantation history significantly affects class II anti-HLA levels, blood transfusion raises class I levels. CONCLUSIONS: Solid organ transplantation appears to have the strongest HLA alloimmunization effect followed by pregnancy and blood transfusion, especially for class II HLA antigens. Patients who were sensitized by more than one sensitization event have a lower chance to have a solid organ transplantation. In this case, identification of donor-specific antibodies and the results of the cross-match tests play an important role both before and postrenal transplantation.

Renal tubular acidosis in renal transplant patients: the effect of immunosuppressive drugs.

BACKGROUND: Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Calcineurine inhibitors (CNIs) increase the frequency of RTA but the frequency of RTA development in kidney transplant recipients receiving mammalian target of rapamycin inhibitors (mTORi) treatment remains unclear. In this study, we aimed to investigate the frequency of RTA in kidney transplant recipients on mTORi and CNI treatment and to compare both groups. MATERIAL AND METHODS: We enrolled 137 adult renal transplant patients - 82 patients on mTORi and 55 patients on CNI who had similar age, sex, posttransplant follow-up period, and graft functions. We recorded the parameters of venous blood gas analysis, including serum pH value, serum bicarbonate (HCO3) concentration, presence of metabolic acidosis defined as low HCO3 (<22 mEq/L), and serum pH value (<7.35), as well as base excess and urine pH at last follow-up. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap. RESULTS: The mean age of our study population was 41.2±11.3 years. RTA frequency was 35% in the mTORi group and 41% in the CNI group. mTORi and CNI groups did not differ significantly in terms of the development of metabolic and renal tubular acidosis. Type I RTA was common in both groups. RTA was affected by duration of time since transplantation and graft functions in both groups. CONCLUSIONS: The rates of RTA development in patients on long-term CNI and mTORi treatment were similar.

The relation between serum testosterone levels and cardiovascular risk factors in patients with kidney transplantation and chronic kidney disease.

The objective of the study is to evaluate the relationship between serum testosterone levels and cardiovascular risk factors (CVRF) in patients after kidney transplantation and with chronic kidney disease (CKD). Seventy-five male patients, aged between 18 and 68 years, who had kidney transplantation at least six months earlier, were enrolled into the study. Only renal transplant recipients and CKD patients with a creatinine level of <2.5 mg/dL were included in this study. Patients were divided into three groups as patients receiving calcineurine inhibitors (CNIs) and Mammalian target of rapamycin inhibitors (m-TORi) and CKD. Serum ceatinine, testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), triglyceride (TG) as well as left ventricle mass (LVM), left ventricle mass index (LVMI), left atrium (LA), inferior vena cava (IVC) inspiratory and expiratory diameters and collapse index (CI) and blood pressure (BP) were evaluated. Serum testosterone levels were significantly higher in the m-TORi and CNIs groups when compared with the CKD cases (P <0.05). When kidney recipients (both groups) were compared with CKD patients, we observed positive outcomes in serum testosterone levels and CVRF at significant levels. There was no significant difference in terms of age, serum creatinine, serum testosterone, FSH, LH, prolactin, hs-CRP, LVMI, TC and TG and between the CNIs and mTORi groups (P >0.05). Serum testosterone levels were independent risk factors affecting IVC collapse index, systolic BP and LA. m-TORi and CNIs drugs might have no negative effect on serum testosterone levels, and improvement of the serum testosterone levels after transplantation might have a positive contribution on cardiac risk factors.

Mesenchymal stem cell therapy in patients with small bowel transplantation: single center experience.

AIM: To study the effects of mesenchymal stem cell (MSC) therapy on the prevention of acute rejection and graft vs host disease following small bowel transplantation. METHODS: In our transplantation center, 6 isolated intestinal transplants have been performed with MSC therapy since 2009. The primary reasons for transplants were short gut syndrome caused by surgical intestine resection for superior mesenteric artery thrombosis (n = 4), Crohn's disease (n = 1) and intestinal aganglionosis (n = 1). Two of the patients were children. At the time of reperfusion, the first dose of MSCs cultured from the patient's bone marrow was passed into the transplanted intestinal artery at a dose of 1000000 cells/kg. The second and third doses of MSCs were given directly into the mesenteric artery through the arterial anastomosis using an angiography catheter on day 15 and 30 post-transplant. RESULTS: The median follow-up for these patients was 10.6 mo (min: 2 mo-max: 30 mo). Three of the patients developed severe acute rejection. One of these patients did not respond to bolus steroid therapy. Although the other two patients did respond to anti-rejection treatment, they developed severe fungal and bacterial infections. All of these patients died in the 2(nd) and 3(rd) months post-transplant due to sepsis. The remaining patients who did not have acute rejection had good quality of life with no complications observed during the follow-up period. In addition, their intestinal grafts were functioning properly in the 13(th), 25(th) and 30(th) month post-transplant. The patients who survived did not encounter any problems related to MSC transplantation. CONCLUSION: Although this is a small case series and not a randomized study, it is our opinion that small bowel transplantation is an effective treatment for intestinal failure, and MSC therapy may help to prevent acute rejection and graft vs host disease following intestinal transplantation.

Determination of a predictive cutoff value of NT-proBNP testing for long-term survival in ED patients with acute heart failure.

OBJECTIVE: The main objective of this study was to determine a predictive cutoff value for plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) that could successfully predict the long-term (4-year) survival of patients with acute heart failure (HF) at the time of admission to the emergency department (ED). To our best knowledge, our study is the first research done to identify a predictive cutoff value for admission NT-proBNP to the prescriptive 4-year survival of patients admitted to ED with acute HF diagnosis. METHODS: NT-proBNP levels were measured in plasma obtained from 99 patients with dyspnea and left ventricular dysfunction upon admission to the ED. The end point was survival from the time of inclusion through 4 years. RESULTS: The mean age of the patients in this study was 71.1 ± 10.3 years; 50 of these patients were female. During the 4-year follow-up period, 76 patients died; survivors were significantly younger than non-survivors (64.26 ± 11.42 years vs 72.83 ± 11.07 years, P = .002). The optimal NT-proBNP cutoff point for predicting 4-year survival at the time of admission was 2300 pg/mL, which had 85.9% sensitivity and 39.1% specificity (95% confidence interval, area under the curve: 0.639, P = .044). CONCLUSION: Elevated NT-proBNP levels at the time of admission are a strong and independent predictor of all-cause mortality in patients with acute HF 4 years after admission. Furthermore, the optimal cutoff level of NT-proBNP used to predict 4-year survival had high sensitivity. However, especially in the case of long-term survival, additional prospective, large, and multicenter studies are required to confirm our results.

Predictive cutoff point of admission N-terminal pro-B-type natriuretic peptide testing in the ED for prognosis of patients with acute heart failure.

OBJECTIVE: The main objective of this study was to determine a cutoff level of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) that could successfully predict the short- and long-term prognosis of patients with acute heart failure at the time of admission to the emergency department. The results of our study are presented in context with previously published literature. We believe that the present study will be useful and salutary for the progress of literature. METHODS: N-terminal pro-B-type natriuretic peptide plasma levels were obtained from 100 patients with shortness of breath and left ventricular dysfunction upon admission to the emergency department. All patients underwent follow-up evaluations 30 days and 1 year after admission. The end point was defined as all-cause mortality. RESULTS: The mean age of the patients in this study was 70.8 ± 11.6 years, and 51% were female. All-cause mortality at the 30-day and 1-year follow-up evaluations was 21.2% and 53.5%, respectively. We determined that the optimal NT-proBNP cutoff point for predicting 30-day mortality at the time of admission was 9152.4 pg/mL, with a 71.4% sensitivity and an 81.3% specificity (95% confidence interval, area under the curve: 0.726; P = .002). The optimal NT-proBNP cutoff point for predicting 1-year mortality at the time of admission was 3630.5 pg/mL, with an 83.0% sensitivity and a 52.2% specificity (95% confidence interval, area under the curve: 0.644; P = .014). CONCLUSION: Elevated NT-proBNP levels at the time of admission are a strong and independent predictor of all-cause mortality in patients with acute heart failure at 30 days and 1 year after admission. Furthermore, the optimal cutoff level of NT-proBNP used to predict 30-day and 1-year mortality had high sensitivity.