Introduction
Several automated coagulation analyzers are available for laboratory use. In a university hospital central laboratory, we compared four different instruments. The results for global ...coagulation assays are presented here.
Methods
ACL TOP 750 CTS (Instrumentation Laboratory), Atellica COAG 360 (COAG 360), BCS XP (both Siemens Healthineers), and cobas t 711 (Roche Diagnostics) were compared. For inter‐instrument comparison, five basic coagulation parameters were analyzed in 476 patient plasma samples. Additional assessments included precision testing using commercial control samples and plasma pools, analysis time for a defined set of samples, sample capacity testing, minimum required sample volumes, and detection quality for hemolytic, icteric, or lipemic (HIL) interferences.
Results
Good concordance between different instruments was evident from Bland–Altman plots and comparison of data from each instrument with the overall median (τ≥0.8). Shortest analysis times were found for BCS XP and COAG 360, COAG 360 revealed highest sample capacity. Observed required sample volumes were broadly in line with manufacturer specifications and varied according to instrument configurations. HIL detection differed between instruments and was best with ACL TOP 750 CTS.
Conclusion
The four analyzers showed similarly high levels of concordance, although some variations were apparent. The most significant differences between the instruments were found in analysis times and sample capacity. Analyzer capabilities must be considered when selecting laboratory equipment and defining algorithms for clinical practice.
As transarterial chemoembolization (TACE) therapy is an effective locoregional treatment for patients with advanced liver cancer, prognostic biomarkers are highly needed for pretherapeutic ...stratification of patients to TACE therapy. Sera of 50 prospectively and consecutively included patients with hepatocellular carcinoma (HCC) undergoing TACE were taken before and 24 h after TACE application. Levels of liver-specific, tumor-related, and cell death biomarkers were analyzed and correlated with overall patient survival. The study was particularly focused on patients treated by TACE with palliative intention (
N
= 38). Sixteen of 38 patients died within 1 year after TACE, 22 were still alive. In univariate analysis, high levels of cytokeratin 19-fragments (CYFRA 21-1), alpha fetoprotein (AFP), and low choline esterase (CHE) levels measured before and 24 h after TACE were correlated with unfavorable outcome. Further high pretherapeutic lactate dehydrogenase (LDH), aspartate-aminotransferase, and bilirubin levels as well as high 24 h C-reactive protein values were associated with poor survival. In multivariate analysis of clinical and only pretherapeutic biomarkers, AFP, CHE, and LDH showed to be independent prognostic parameters. When additionally 24 h values were included, CHE (24 h) and AFP (24 h) were the strongest independent prognostic biomarkers with a slightly higher prognostic power (Akaike’s information criterion 90.3 vs. 92.7). The combination of AFP, CHE, and LDH enables efficient pretherapeutic stratification of HCC patients in advanced tumor stage for TACE therapy.
Background & Aims Colonoscopy is the preferred screening test for colorectal neoplasia; the fecal occult blood test (FOBT) detects neoplasias with low levels of sensitivity. Computed tomographic ...colonography detects neoplasias with high levels of sensitivity but involves exposure to radiation. We investigated whether magnetic resonance colonography (MRC) can be used to screen for colorectal adenomas and cancers. Methods We analyzed data from 286 asymptomatic adults (40–82 years old) who underwent 3 Tesla MRC and colonoscopic examinations on the same day. FOBT was performed before bowel preparation. Colonoscopists were initially blinded to the findings on MRC and unblinded after withdrawal from the respective segments. Sensitivities for adenoma and per-patient sensitivities and specificities were calculated based on the unblinded results of colonoscopy. Results We detected 133 adenomas and 2 cancers in 86 patients; 37 adenomas were ≥6 mm, and 20 adenomas were advanced. Sensitivities of MRC and colonoscopy for adenomas ≥6 mm were 78.4% (95% confidence interval CI, 61.8–90.2) and 97.3% (95% CI, 85.8–99.9); for advanced adenomas these values were 75% (95% CI, 50.9–91.3) and 100% (95% CI, 83.2–100.0), respectively. MRC identified 87.1% (95% CI, 70.2–96.4), colonoscopy 96.8% (95% CI, 83.3–99.9), and FOBT 10.0% (95% CI, 2.1–26.5) of individuals with adenomas ≥6 mm and 83.8% (95% CI, 58.6–96.4), 100% (95% CI, 81.5–100.0), and 17.6% (95% CI, 3.8–43.4) of individuals with advanced neoplasia. Specificities of MRC, colonoscopy, and FOBT for individuals with adenomas ≥6 mm were 95.3% (95% CI, 91.9–97.5), 96.9% (95% CI, 93.9–98.6), and 91.8% (95% CI, 87.6–94.9), respectively. Conclusions 3 Tesla MRC detects colorectal adenomas ≥6 mm and advanced neoplasia with high levels of sensitivity and specificity. Although MRC detects colorectal neoplasia with lower levels of sensitivity than colonoscopy, it strongly outperforms one-time FOBT.
Highlights • High correlation coefficient comparing piperacillin and tazobactam trough levels. • However, piperacillin/tazobactam quotients varied between ca. 1 and 10. • To ensure free tazobactam >4 ...mg/L, piperacillin trough levels ≥70 mg/L should be reached.
Carcinoembryonic antigen (CEA) is the only established serum biomarker for colorectal cancer (CRC). To facilitate therapy decisions and improve the overall survival of CRC patients, prognostic ...biomarkers are required.
We studied the prognostic value of five different cell free circulating DNA (fcDNA) fragments. The potential markers were ALU115, ALU247, LINE1-79, LINE1-300 and ND1-mt.
The copy numbers of the DNA fragments were measured in the peripheral blood serum of 268 CRC patients using qPCR, the results were compared to common and previously described markers.
We found that ALU115 and ALU247 fcDNA levels correlate significantly with several clinicopathological parameters. An increased amount of ALU115 and ALU247 fcDNA fragments coincides with methylation of HPP1 (P< 0.001; P< 0.01), which proved to be a prognostic marker itself in former studies and also with increased CEA level (both P< 0.001). ALU115 and ALU247 can define patients with poor survival in UICC stage IV (ALU115: HR = 2.9; 95% Cl 1.8-4.8, P< 0.001; ALU247: HR = 2.2; 95% Cl 1.3-3.6; P= 0.001). Combining ALU115 and HPP1, the prognostic value in UICC stage IV is highly significant (P< 0.001).
This study shows that an increased level of ALU fcDNA is an independent prognostic biomarker for advanced colorectal cancer disease.
Background: Cancer antigen 125 (CA125) is the best known single tumor marker for ovarian cancer (OC). We investigated whether the additional information of the human epididymis protein 4 (HE4) ...improves diagnostic accuracy. Methods: We retrospectively analyzed preoperative sera of 109 healthy women, 285 patients with benign ovarian masses (cystadenoma: n=78, leimyoma: n=66, endometriosis: n=52, functional ovarian cysts: n=79, other: n=10), 16 low malignant potential (LMP) ovarian tumors and 125 OC (stage I: 22, II: 15, III: 78, IV: 10). CA125 was analyzed using the ARCHITECT system, HE4 using the ARCHITECT(a) system and EIA(e) technology additionally. Results: The lowest concentrations of CA125 and HE4 were observed in healthy individuals, followed by patients with benign adnexal masses and patients with LMP tumors and OC. The area under the curve (AUC) for the differential diagnosis of adnexal masses of CA125 alone was not significantly different to HE4 alone in premenopausal (CA125: 86.7, HE4(a): 82.6, HE4(e): 81.6% p>0.05) but significantly different in postmenopausal CA125: 93.4 vs. HE4(a): 88.3 p=0.023 and vs. HE4(e): 87.8% p=0.012 patients. For stage I OC, HE4 as a single marker was superior to CA125, which was the best single marker in stage II-IV. The combination of CA125 and HE4 using risk of malignancy algorithm (ROMA) gained the highest sensitivity at 95% specificity for the differential diagnosis of adnexal masses CA125: 70.9, HE4(a): 67.4, HE4(e): 66.0, ROMA(a): 76.6 and ROMA(e): 74.5%, especially in stage I OC CA125: 27.3, HE4(a): 40.9, HE4(e): 40.9, ROMA(a): 45.5 and ROMA(e): 45.5%. Conclusions: CA125 is still the best single marker in the diagnosis of OC. HE4 alone and even more the combined analysis of CA125 and HE4 using ROMA improve the diagnostic accuracy of adnexal masses, especially in early OC.
Carcinoembryonic antigen (CEA) remains the only recommended biomarker for follow-up care of colorectal cancer (CRC), but besides CEA, several other serological parameters have been proposed as ...prognostic markers for CRC. The present retrospective analysis investigates a comprehensive set of serum markers with regard to cancer-specific survival (CSS) and disease-free survival (DFS). A total of 472 patients with colon cancer underwent surgery for curative intent between January 1988 and June 2007. Preoperative serum was analyzed for the following parameters: albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin (βhCG), bilirubin, cancer antigen 125 (CA 125), cancer antigen 19-9 (CA 19-9), CA 72-4, CEA, C-reactive protein (CRP), cytokeratin-19 soluble fragment (CYFRA 21-1), ferritin, gamma-glutamyltransferase (γGT), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate dehydrogenase (LDH), serum amyloid A (SAA), and 25-hydroxyvitamin D. After a median follow-up period of 5.9 years, the overall 3- and 5-year CSS was 91.7 and 84.9 % and DFS rates were 82.7 % (3 years) and 77.6 % (5 years). Multivariate analyses confirmed preoperative CEA as an independent prognostic factor with regard to CSS and DFS. CA 19-9 and γGT also provided prognostic value for CSS and DFS, respectively. Younger age was negatively associated with DFS. According to UICC stage, CEA provided significant prognostic value with regard to CSS and DFS, while CA 19-9 was only prognostic for CSS. Combined analysis is able to identify patients with favorable prognosis. In addition to tumor baseline parameters, preoperative CEA could be confirmed as prognostic marker in colon cancer. CA 19-9 and γGT also provide additional prognostic value with regard to survival and recurrence in stage III and stage I disease, respectively. The combined use of CEA together with CA 19-9 and γGT improve risk-adapted post-op surveillance.
: The aim of the present study was to examine whether the recently introduced heparin‐mediated extracorporeal low‐density lipoprotein precipitation (HELP) apheresis system Plasmat Futura (since 2001) ...was comparable to Plasmat Secura system, used to date, in its efficiency to remove atherogenic components, its ease of handling and operating as well as clinical safety and patient compliance. Coronary heart disease (CHD) patients (N = 21) were first treated with Plasmat Secura system and 13 of them were then randomly switched over to the upgraded Plasmat Futura system. Eight patients remained on Secura system. All together, 40 Futura treatments and 40 Secura treatments were performed. Blood samples were collected immediately before and after each apheresis therapy. Our data showed no significant differences in the reduction of plasma low‐density lipoprotein, lipoprotein (a) and fibrinogen by Plasmat Futura and Secura system (P > 0.05). However, the major advantages of Plasmat Futura system are the ready‐to‐use sterile dialysis solutions instead of reverse osmosis device in Plasmat Secura, which ensures flexibility and lower risk of cross infections. Long‐term tolerance and safety parameters showed no significant difference (P > 0.05). On the basis of our studies, Plasmat Futura system is easy to use, shows no adverse events and is comparable to Plasmat Secura in its capacity to remove proatherogenic plasma factors.
Circulating nucleosomes, complexes of DNA and histones, are recognized as a potential new diagnostic tool for therapy monitoring of cancer disease and as prognostic marker in other acute diseases. ...Because many studies are carried out retrospectively on serum samples collected earlier, we tested the stability of nucleosomes during long-term storage at -70 degrees C.
Never-thawed aliquots of 154 stabilized serum samples from cancer patients which had been stored between 11/1999 and 07/2001 at -70 degrees C were analyzed by ELISA six to nine months after collection and for a second time in 11/2006, with a median interval of 64.8 months (+/-5.5 months) between the measurements.
Nucleosome levels of the second measurement (median 220.0 ng/ml) were significantly lower than those of the first measurement (354.0 ng/ml; p<0.0001) exhibiting a median decrease of 32.0% (mean 29.7%+/-39.7%). Single concentrations of both measurements correlated well (R=0.92; p<0.0001). Individual courses of eight cancer patients showed a parallel downshifting of the nucleosome signal. The concordance rate of parallel increases and decreases was 89%.
Retrospective studies on nucleosomes in serum can be performed if samples derive from homogeneous time intervals and preanalytical protocols are respected.
Several independent serum biomarkers have been proposed as prognostic and/or predictive markers for colorectal cancer (CRC). To this date, carcinoembryonic antigen (CEA) remains the only recommended ...serological CRC biomarker. The present retrospective analysis investigates the prognostic value of several serum markers. A total of 256 patients with rectal cancer underwent surgery for curative intent in a university cancer center between January 1988 and June 2007. Preoperative serum was retrospectively analyzed for albumin, alkaline phosphatase (aP), beta-human chorionic gonadotropin, bilirubin, CA 125, cancer antigen 19-9, cancer antigen 72-4 (CA 72-4), CEA, CRP, CYFRA 21-1, ferritin, gamma-glutamyl transpeptidase, glutamate oxaloacetate transanunase, glutamate pyruvate transaminase, hemoglobin, haptoglobin, interleukin-6, interleukin-8, creatinine, lactate-dehydrogenase, serum amyloid A (SAA), and 25-hydroxyvitamin D. Cancer-specific survival (CSS) and disease-free survival (DFS) were estimated. Median follow-up time was 8.4 years. Overall 3- and 5-year CSS was 88.6 and 78.9 %, respectively. DFS rates were 72.8 % (3 years) and 67.5 % (5 years). Univariate analysis of CSS indicated aP, CA 72-4, CEA, and SAA as prognostic factors, while aP, CEA, and SAA were also prognostic with regard to DFS. Multivariate analysis confirmed SAA together with T and N stage as prognostic factors. According to UICC stage, CEA and SAA add prognostic value in stages II and III with regard to DFS and CSS, respectively. The combined use of CEA and SAA is able to identify patients with favorable and poor prognosis. In addition to tumor baseline parameters, routine analysis of SAA together with CEA provided markedly improved prognostic value on CSS and DFS in resected rectal cancer.
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