Significant elevations of serum amylase caused by macroamylase: Case reports and detection possibilities.

BACKGROUND: The presence of isolated elevated serum amylase levels can be caused by high molecular mass complexes. We describe 13 cases of hyperamylasemia detected in adult patients without clinical symptoms of a pancreatic disorder. Five of them were thoroughly examined using different tools for the detection of macrocomplexes. METHODS: We performed both screening and more advanced methods of macroamylase detection, including polyethylene glycol precipitation, sample storage at 4°C and separation by gel filtration. RESULTS: The presence of macroamylase in the suspected samples was confirmed by the methods described, except for the sample storage at 4°C. In this method, the enzyme activity did not decrease. The polyethylene glycol precipitation activity (% PPA) averaged 89.1% for amylase, whereas the control samples averaged 30.7%. Gel filtration chromatography confirmed an IgA macroamylase peak in three samples and an IgG macroamylase peak in two samples. CONCLUSION: The presence of macroamylase should be suspected whenever the clinical history and condition of the patient do not match the measured enzyme value to avoid diagnostic errors and unnecessary invasive examinations. The presence of macrocomplexes is considered a benign process that may occur in apparently healthy individuals. Cooperation between clinicians and laboratory staff is necessary.

Galectin-3 as an independent prognostic factor after heart transplantation.

BACKGROUND: Galectin-3 (GAL3) is linked to the prognosis of patients with heart failure and after heart transplantation (HTx). We assessed the prognostic role of GAL3 in a long-term follow-up after HTx. METHODS: HTx patients (N = 121) were evaluated in a single-center, noninterventional, prospective, observational study. The median follow-up was 96 months (2942 days, interquartile range (IQR) 2408-3264 days), and 40 patients died. GAL3 was measured before HTx, +10 days after HTx, and during the first posttransplant year. Survival analysis (all-cause mortality) was performed with adjustments for clinical and laboratory variables. RESULTS: The median pretransplant GAL3 level was 18.0 µg/L (IQR 14.0-25.9), and higher values were associated with older age, worse kidney function, left ventricular assist device use before HTx, a higher IMPACT score, and mortality. Increased pretransplant GAL3 predicted shorter survival time (HR 2.05, 95% CI 1.09-3.85, p < .05). Similar prognostic power had GAL3 on the 10th posttransplant day (HR 2.03, 95% CI 1.08-3.82, p < .05). GAL3 was an independent predictor of death after adjustment for clinical variables (age, infection, diabetes, smoking, IMPACT score, and troponin). CONCLUSIONS: GAL3 was significantly associated with all-cause mortality after adjusting for clinical and laboratory variables and may serve as an additional prognostic biomarker.

Changes in Sepsis Biomarkers after Immunosuppressant Administration in Transplant Patients.

Sepsis biomarkers change continuously during the postoperative period. We aimed to demonstrate the influence of immunosuppressants after transplantation (Tx) on presepsin, procalcitonin, CRP, white blood cells, and IL-6. A group of 140 patients after major surgery (86 non-Tx, 54 Tx) without any signs of sepsis or infectious complications was followed for 7 days. The changes in biomarkers were analyzed with respect to the type of surgery, organ, and induction immunosuppressant used (antithymocyte globulin, corticosteroids, or basiliximab/rituximab). Concentrations (95th percentiles) of presepsin and procalcitonin were higher in the Tx group (presepsin: Tx < 2380 vs. non-Tx < 1368 ng/L, p < 0.05; procalcitonin: <28.0 vs. 3.49 µg/L, p < 0.05). In contrast, CRP and IL-6 were lower in the Tx group (CRP: Tx < 84.2 vs. non-Tx < 229 mg/L, p < 0.05; IL-6: <71.2 vs. 317 ng/L, p < 0.05). Decreases in CRP and IL-6 were found for all immunosuppressants, and procalcitonin was increased after antithymocyte globulin and corticosteroids. Negligible changes were found for white blood cells. Different responses of presepsin, procalcitonin, CRP, and IL-6 were therefore found in patients without any infectious complications after major surgery or transplantation. Immunosuppression decreased significantly IL-6 and CRP in comparison to non-Tx patients, while procalcitonin was increased after corticosteroids and antithymocyte globulin only. Cautious interpretation of sepsis biomarkers is needed in the early posttransplant period. This work was conducted as a noninterventional (nonregistered) study.

Spironolactone-furosemide combination therapy and acid-base disorders in liver cirrhosis patients
.

OBJECTIVE: Respiratory alkalosis (RA) and dilutional hyperchloremic acidosis (DHA) are the most common acid-base balance (ABB) disorders in patients with liver cirrhosis. The aims of this study were to clarify whether RA develops in relation to DHA via respiratory compensation of metabolic acidosis and whether spironolactone in combination with low-dose furosemide - diuretics known to ameliorate DHA - positively affects RA in liver cirrhosis patients. MATERIALS AND METHODS: 59 patients with advanced cirrhosis were divided into two groups. Group D consisted of individuals (urine sodium concentration (UNa+) > 20 mmol/L) who responded to combination therapy consisting of spironolactone and low-dose furosemide. The non-D group consisted of individuals (UNa+ ≤ 20 mmol/L) who either did not respond to the treatment or who were not administered it. In both groups, we examined serum and urine concentrations of electrolytes and ABB parameters, including SNa+-SCl- and SNa+/SCl- values. RESULTS: In group D, we found a statistically significant relationship between pCO2 and SHCO3-: r = 0.756 (p < 0.001) and between pCO2 and SNa+-SCl-: r = 0.522 (p = 0.001). Neither Salb nor the corrected anion gap were associated with changes in SHCO3- or pCO2 values. Although SHCO3- values were normal, abnormal pCO2 values were observed in one third of group D patients. Based on multivariable analysis, SHCO3- proved to be a statistically significant influencing factor on pCO2 values. CONCLUSION: DHA contributes to the development of RA in individuals with liver cirrhosis. Reducing DHA by means of effective diuretic therapy comprising spironolactone and furosemide has a beneficial effect on RA in such patients.

Presepsin: what is important for correct interpretation.

INTRODUCTION: Presepsin (soluble CD14 subtype) is a new biomarker of infection and sepsis. Correct interpretation is based on the knowledge of analytical reliability, biological variation, decision limits, and diagnostic effectivity. AIM: The aim of the study was to verify analytical precision of presepsin measurements, to assess biological variation in healthy subjects, to verify reference and decision limits, to assess diagnostic effectivity, and to compare data with commonly used septic biomarkers - procalcitonin (PCT), CRP and interleukin 6 (IL6). MATERIAL AND METHODS: Analyti-cal precision (repeatability and intermediate precision) was estimated by repeated measurements of commercial control materials. Biological variation was evaluated in a group of 20 healthy volunteers in a 7-week experi-ment. Reference ranges were extracted from the literature and compared with data from healthy subjects. RESULTS: Precisions of presepsin measurements were 2.0-4.0 % (“within-run”) and 6.1-9.5 % (“between-run”). Intraindividual biological variation of presepsin was 22.3 %, interindividual variation 20.8 %. Index of individuality was 1.07, reference change value (RCV - critical difference) was 72 %. Upper reference limit was around 180 ng/l. CONCLUSION: Ana-lytical quality of presepsin measurement is suitable for clinical use. Biological variation parameters enable the use of reference limits, upper reference limit of presepsin is around 180 ng/l. None of the tested biomarkers has universal cut-off value, multiple biomarkers are needed and repeated measurements are advisable.

Falsely elevated human epididymis protein 4 results and Risk of Ovarian Malignancy Algorithm in polymorbid women after solid organ transplantation: A pilot and case-control study.

BACKGROUND: Cancer prevention is essential after transplantation (Tx). The use of HE4 and Risk of Ovarian Malignancy Algorithm (ROMA) is recommended as a tool for selective ovarian cancer screening; however, creatinine is a known confounder. This study assessed the reliability of HE4, CA125, and ROMA after Tx. METHODS: We matched a total of 202 women without gynecological malignancies and 236 men by age and serum creatinine. Each pair consisted of a patient after Tx (kidney, liver, heart, and pancreas) and a diseased but non-Tx consecutive patient. Serum HE4, CA125 (Roche Cobas 6000), and creatinine (enzymatic, Abbott Architect) were measured in all patients. RESULTS: Creatinine correlated with HE4 (women: r = .864, P < .0001; men: r = .848, P < .0001). Age correlated slightly with HE4 in women (r = .250, P < .005) and men (r = .240, P < .0005). HE4 in women after Tx (median of 84.8 pmol/L) was significantly higher than non-Tx women (53.7 pmol/L, P < .0001) in the reference range of serum creatinine. Neither HE4 nor CA125 correlated with tacrolimus concentration, but anemia, hyperparathyroidism, kidney, liver, and lung diseases were possible confounders for HE4 after transplantation (P < .05). CONCLUSION: Human epididymis protein 4 (HE4) was significantly increased in women after solid organ transplantation compared to levels without transplants matched by age and serum creatinine. HE4 results may be misleading in these patients.

[Remarks on biomarkers of cardiovascular risk]. / Poznámky k analytice biomarkeru kardiovaskulárního rizika.

Authors describe state-of-the-art in the routine laboratory diagnostics of cardiovascular risk with special emphasis on metrology, traceability, external quality assessment, biological variation, and reference change value. While analytical quality of total cholesterol, triglycerides, glucose, and HbA1c is satisfactory, improvements are needed for HDL-cholesterol, LDL-cholesterol, apolipoprotein A1, apolipoprotein B, Lp(a), and LpPLA2 measurements. Biological variation is a strong player in the lipid diagnostics, because reference change value is above 20 % for majority of biomarkers. Current methodology for the measurement of remnant cholesterol is far from optimum and standardization is therefore needed.Key words: biological variation - clinical chemistry - interpretation - lipid profile - metrology - remnant cholesterol.

Serial measurement of presepsin, procalcitonin, and C-reactive protein in the early postoperative period and the response to antithymocyte globulin administration after heart transplantation.

Differentiation between systemic inflammatory response syndrome and sepsis in surgical patients is of crucial significance. Procalcitonin (PCT) and C-reactive protein (CRP) are widely used biomarkers, but PCT becomes compromised after antithymocyte globulin (ATG) administration, and CRP exhibits limited specificity. Presepsin has been suggested as an alternative biomarker of sepsis. This study aimed to demonstrate the role of presepsin in patients after heart transplantation (HTx). Plasma presepsin, PCT, and CRP were measured in 107 patients serially for up to 10 days following HTx. Time responses of biomarkers were evaluated for both noninfected (n=91) and infected (n=16) patients. Areas under the concentration curve differed in the two groups of patients for presepsin (P<.001), PCT (P<.005), and CRP (P<.001). The effect of time and infection was significant for all three biomarkers (P<.05 all). In contrast to PCT, presepsin was not influenced by ATG administration. More than 25% of noninfected patients had PCT above 42 µg/L on the first day, and the peak concentration of CRP in infected patients was reached on the third post-transplant day (median 135 mg/L). Presepsin seems to be as valuable a biomarker as PCT or CRP in the evaluation of infectious complications in patients after HTx.

Procalcitonin Dynamics After Long-Term Ventricular Assist Device Implantation.

BACKGROUND: Infectious complications (IC) are one of the main causes of worsening prognosis after long-term ventricular assist device (LVAD) implantation. Procalcitonin (PCT) is widely used for diagnosis of a bacterial infection. The objective of this study was to assess PCT dynamics after LVAD surgery and their relationship to the infectious complications. METHODS: A total of 25 consecutive patients indicated for LVAD implantation as a bridge to heart transplant were included. Procalcitonin levels were prospectively assessed before surgery and during the postoperative period (day 1, 2, 14 and 30). Values were compared according to the presence of IC. RESULTS: Procalcitonin levels were low before surgery, raised significantly within 1st and 2nd day after operation and decreased in the 14th and 30th days back to the baseline. There was no significant difference in PCT values between patients with or without IC as well as with or without right ventricle assist device (RVAD). Acute renal failure (ARF) increased PCT significantly only 14 days after LVAD implantation. In patients with ARF and/or RVAD we observed significantly higher PCT values in the 2nd, 14th and 30th day after operation. In subjects with IC and/or ARF and/or RVAD we also observed significantly elevated PCT concentrations 2 and 14 days after surgery. CONCLUSIONS: Our data show that the ability of PCT to detect IC in patients after LVAD implantation is limited and its concentrations more likely correlate with postoperative complications in general.

Multiple qualitative and quantitative methods for free light chain analysis are necessary as first line tests for AL amyloidosis.

The objective of this study was to demonstrate the necessity of using different methods for amyloidogenic light chain detection. Serum and urine agarose gel electrophoresis and immunofixation, as well as serum free light chain (FLC) immunoassay measurements, were evaluated in a patient with verified multiple myeloma and consequent AL amyloidosis confirmed by Congo red staining and immunofluorescence techniques. Conventional chemistry tests [serum and urine electrophoresis (SPE and UPE); serum and urine immunofixation (SIFE and UIFE)] were inconclusive. Only quantitative FLC immunoassay (serum free light chain immunoanalysis, SFLC) provided correct diagnostic information. A combination of gel-based SIFE and UIFE with more novel quantitative FLC immunoassays appears necessary when searching for monoclonal immunoglobulin light chain-related diseases.

The role of timely measurement of galectin-3, NT-proBNP, cystatin C and hsTnT in predicting prognosis and heart function after heart transplantation.

BACKGROUND: Changes of biomarkers measured soon after heart transplantation (HTx) can reflect different processes: cardiomyocyte necrosis (troponins, high-sensitivity cardiac TnT and TnI), heart function (natriuretic peptides, BNP and NT-proBNP), fibrosis (galectin-3 and ST2), and global cardiorenal risk (cystatin C). We assessed the prognostic role of hsTnT, NT-proBNP, galectin-3 and cystatin C during the early post-transplant period. METHODS: A total of 121 consecutive post-HTx patients were assessed. The main outcomes were survival, left ventricular ejection fraction (LVEF) and rejection periods. Survival was assessed after intermediate (12 months) and long periods (total follow-up during study, median of survival 763 days, IR 527-1038 days). LVEF was assessed 12 months after HTx. Rejection was evaluated during follow-up. We report biomarker concentrations measured 10 days and 12 months after HTx. RESULTS: Ten days after HTx, cystatin C and hsTnT predicted death both under univariable and multivariable analysis. These two biomarkers along with galectin-3 were increased in patients with decreased LVEF measured 1 year after HTx. NT-proBNP did not show early prognostic power. None of the measured biomarkers predicted rejection, but hsTnT and NT-proBNP were increased significantly 12 months after HTx in patients with at least one rejection. CONCLUSIONS: Cystatin C and hsTnT measured 10 days after HTx can provide prognostic information on survival and galectin-3 measured at the same time may display a relationship to heart function assessed 1 year after HTx. Further study should be carried out in a large cohort of patients.

Analysis of Four Automated Urinalysis Systems Compared to Reference Methods.

BACKGROUND: The aim of this study was to compare four automated urinalysis systems: the Iris iQ200 Sprint (Iris Diagnostics, U.S.A.) combined with the Arkray AUTION MAX AX 4030, Iris + AUTION, Arkray AU 4050 (Arkray Global Business, Inc., Japan), Dirui FUS 2000 (Dirui Industrial Co., P.R.C.), and Menarini sediMAX (Menarini, Italy). METHODS: Urine concentrations of protein and glucose (Iris, Dirui) were compared using reference quantitative analysis on an Abbott Architect c16000. Leukocytes, erythrocytes, epithelia, and casts (Iris, Arkray, Diuri, Menarini) were compared to urine sediment under reference light microscopy, Leica DM2000 (Leica Microsystems GmbH, Germany) with calibrated FastRead plates (Biosigma S.r.l., Italy), using both native and stained preparations. RESULTS: Total protein and glucose levels were measured using the Iris + AUTION system with borderline trueness, while the Dirui analysis revealed worse performances for the protein and glucose measurements. True classifications of leukocytes and erythrocytes were above 85% and 72%, respectively. Kappa statistics revealed a nearly perfect evaluation of leukocytes for all tested systems; the erythrocyte evaluation was nearly perfect for the Iris, Dirui and Arkray analyzers and substantial for the Menarini analyzer. The epithelia identification was connected to high false negativity (above 15%) in the Iris, Arkray, and Menarini analyses. False-negative casts were above 70% for all tested systems. CONCLUSIONS: The use of automated urinalysis demonstrated some weaknesses and should be checked by experienced laboratory staff using light microscopy.

[The common position of the Czech professional associations on the consensus of the European Atherosclerosis Society and the European Federation of Clinical Chemistry and Laboratory Medicine regarding investigation on blood lipids and interpretation of their levels]. / Spolecné stanovisko ceských odborných spolecností ke konsenzu European Atherosclerosis Society a European Federation of Clinical Chemistry and Laboratory Medicine k vysetrování krevních lipidu a k interpretaci jejich hodnot.

The aim of this opinion is to summarize and to comment the consensus of the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine, which covers two main areas: 1) whether it is necessary / required to be fasting or non-fasting before blood sampling for lipids measurement, and what are the changes in the concentration of blood lipids during the day; 2) What decision limits (cut off value) of lipids and lipoproteins should be reported from laboratories and what is the recommended procedure for people with extreme / critical blood lipid values. Following parameters are discused: total cholesterol, LDL cholesterol, HDL cholesterol, non-HDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, lipoprotein(a). This opinion should be the object of interest both for professionals in clinical laboratories and for physicians in hospitals and out-patients departments.Key words: apolipoproteins - blood collection - cholesterol - laboratory testing - lipoprotein(a) - cut off limits - triglycerides.

Long-term biological variability of galectin-3 after heart transplantation.

BACKGROUND: Galectin-3 is an emerging biomarker of heart failure and of myocardial fibrosis risk. Monitoring of galectin-3 is essential during treatment with galectin-3 inhibitors. The aim of our study was to assess long-term biological variability in a specific group of unhealthy subjects. METHODS: The biological variability of galectin-3 was measured in a group of 44 patients after heart transplantation (HTx). Six samples were taken from each patient during a 12-month period. Galectin-3 was measured with an Abbott Architect automated immunoassay. RESULTS: Intraindividual (CVi) and interindividual (CVg) variabilities were calculated together with the reference change value (RCV), the log-normal RCV for increase (RCV+), and the log-normal RCV for decrease (RCV-). The CVi, CVg, RCV, RCV+, and RCV- were 28.2%, 35.6%, 78.6%, 116%, and -53.7%, respectively. The index of individuality was 0.79. CONCLUSIONS: The concentrations of galectin-3 in patients followed 12 months after HTx fluctuated around the homeostatic point, with CVi of approximately 28%. RCVs of +116% (log-normal increase) and -54% (log-normal decrease) mean that the concentration of galectin-3 would need to approximately double or decrease by half to indicate a new process.

Analytical evaluation of the automated galectin-3 assay on the Abbott ARCHITECT immunoassay instruments.

BACKGROUND: Galectin-3 is secreted from macrophages and binds and activates fibroblasts forming collagen. Tissue fibrosis is central to the progression of chronic heart failure (CHF). We performed a European multicentered evaluation of the analytical performance of the two-step routine and Short Turn-Around-Time (STAT) galectin-3 immunoassay on the ARCHITECT i1000SR, i2000SR, and i4000SR (Abbott Laboratories). METHODS: We evaluated the assay precision and dilution linearity for both routine and STAT assays and compared serum and plasma, and fresh vs. frozen samples. The reference interval and biological variability were also assessed. Measurable samples were compared between ARCHITECT instruments and between the routine and STAT assays and also to a galectin-3 ELISA (BG Medicine). RESULTS: The total assay coefficient of variation (CV%) was 2.3%-6.2% and 1.7%-7.4% for the routine and STAT assays, respectively. Both assays demonstrated linearity up to 120 ng/mL. Galectin-3 concentrations were higher in plasma samples than in serum samples and correlated well between fresh and frozen samples (R=0.997), between the routine and STAT assays, between the ARCHITECT i1000 and i2000 instruments and with the galectin-3 ELISA. The reference interval on 627 apparently healthy individuals (53% male) yielded upper 95th and 97.5th percentiles of 25.2 and 28.4 ng/mL, respectively. Values were significantly lower in subjects younger than 50 years. CONCLUSIONS: The galectin-3 routine and STAT assays on the Abbott ARCHITECT instruments demonstrated good analytical performance. Further clinical studies are required to demonstrate the diagnostic and prognostic potential of this novel marker in patients with CHF.

How to verify the analytical and clinical performance of ELISA immunoanalysis in the real laboratory practice. PCSK9 as an example.

BACKGROUND: Manufacturers and diagnostic companies often recommend on-site verification of analytical performance in the clinical laboratory. The validation process used by manufacturers is rarely described in detail, and certain information on analytical performance is missing from the product sheet, especially for immunoanalytical methods. We describe an approach to the detailed validation of an ELISA method for the measurement of proprotein convertase subtilisin/kexin type 9 (PCSK9) plasma concentrations. We compared manufacturers' claims of analytical performance with data obtained in the field laboratory using several approaches. METHODS: We used the Human Proprotein Convertase 9/PCSK9 Quantikine ELISA diagnostic kit (R&D systems, Bio-Techne Ltd., Abingdon Science Park, Abingdon, UK) and three levels of quality control solution Quantikine Immunoassay Control Group 235 (R&D systems, Bio-Techne Ltd., Abingdon Science Park, Abingdon, UK) to verify precision. We measured the concentration of PCSK9 using the DS2 ELISA Reader (Dynex Technologies GmbH, Denkendorf, Germany). We used analysis of variance (ANOVA) and the R statistical package (R core team, version 1.4.5). Statistical analysis and terminology were performed according to protocol CLSI EP15-A3, and the reference interval was checked according to CLSI/IFCC C28-A3c. RESULTS: We found a significant difference between the manufacturer's claims of analytical performance and real data measured in the routine clinical laboratory. The calculated CV (%) for repeatability (calculated by simple estimation of the mean and SD, as used by the manufacturer) was between 5.5% and 7.4%, but the manufacturer's claim was between 4.1% and 6.5%. Using ANOVA, the true repeatability was between 5.0% and 6.9%. Similarly, ANOVA revealed values of CV (%) for within-laboratory imprecision between 6.5% and 9.1%, while the manufacturer's claims were between 4.1% and 5.9%. The recovery ranged from 105.5% to 121.8%. The manufacturer's recommended reference interval was checked and we didn't find any significant difference between men and women. CONCLUSIONS: We describe a comprehensive approach to verify the analytical performance of an ELISA method using the measurement of PCSK9 plasma concentration as an example. We found differences between the results of this approach based on the CLSI EP15-A3 protocol and data provided by the manufacturer. We recommend the verification of analytical performance by more complex statistical tools in laboratory practice.

Biological variation of PIVKA-II in blood serum of healthy subjects measured by automated electrochemiluminescent assay.

Background: Prothrombin/Protein Induced by Vitamin K Absence-II (PIVKA-II) is a candidate biomarker of hepatocellular cancer, recommended both for diagnostics and monitoring. The aim was to evaluate biological variation (BV) of serum PIVKA-II. Methods: Within-subject (CVI) and between-subject (CVG) BV estimates were assessed in 14 healthy volunteers in a 6-week protocol. Serum concentrations of PIVKA-II were measured by a Roche Elecsys PIVKA-II diagnostic kit (cobas e8000). Precision (CVA) was assessed from duplicate measurements of all volunteers' samples. Two methods were used for the estimation of CVI: SD-ANOVA and CV-ANOVA method. We calculated the index of individuality (II) and reference change value. The experiment was fully compliant with EFLM database checklist. Results: The CVI of PIVKA-II in healthy persons, as calculated by two statistical methods, were 8.2% (SD-ANOVA with CVA of 3.2%) and 9.4% (CV-ANOVA) with CVA of 2.7%). The CVG was 19.5% (SD-ANOVA), and respective II and RCV were 0.42 and 24.4%. Conclusions: CVI and CVG of PIVKA-II were 8.2% and 19.5%, respectively, with CVA below 4%. The low II and RCV below 25% enable the use of this biomarker both for diagnostics and monitoring. More data are needed before the introduction of PIVKA-II into clinical practice.

Circulating beta-hydroxybutyrate levels in advanced heart failure with reduced ejection fraction: Determinants and prognostic impact.

AIMS: Patients with heart failure (HF) display metabolic alterations, including heightened ketogenesis, resulting in increased beta-hydroxybutyrate (ß-OHB) formation. We aimed to investigate the determinants and prognostic impact of circulating ß-OHB levels in patients with advanced HF and reduced ejection fraction (HFrEF). METHODS AND RESULTS: A total of 867 patients with advanced HFrEF (age 57 ± 11 years, 83% male, 45% diabetic, 60% New York Heart Association class III), underwent clinical and echocardiographic examination, circulating metabolite assessment, and right heart catheterization (n = 383). The median ß-OHB level was 64 (interquartile range [IQR] 33-161) µmol/L (normal 0-74 µmol/L). ß-OHB levels correlated with increased markers of lipolysis (free fatty acids [FFA]), higher natriuretic peptides, worse pulmonary haemodynamics, and lower humoral regulators of ketogenesis (insulin/glucagon ratio). During a median follow-up of 1126 (IQR 410-1781) days, there were 512 composite events, including 324 deaths, 81 left ventricular assist device implantations and 107 urgent cardiac transplantations. In univariable Cox regression, increased ß-OHB levels (T3 vs. T1: hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.72, p = 0.002) and elevated FFA levels (T3 vs. T1: HR 1.39, 95% CI 1.09-1.79, p = 0.008) were both predictors of a worse prognosis. In multivariable Cox analysis evaluating the simultaneous associations of FFA and ß-OHB levels with outcomes, only FFA levels remained significantly associated with adverse outcomes. CONCLUSIONS: In patients with advanced HFrEF, increased plasma ß-OHB correlate with FFA levels, worse right ventricular function, greater neurohormonal activation and other markers of HF severity. The association between plasma ß-OHB and adverse outcomes is eliminated after accounting for FFA levels, suggesting that increased ß-OHB is a consequence reflecting heightened lipolytic state, rather than a cause of worsening HF.

Accuracy and Feasibility of Real-time Continuous Glucose Monitoring in Critically Ill Patients After Abdominal Surgery and Solid Organ Transplantation.

OBJECTIVE: Glycemia management in critical care is posing a challenge in frequent measuring and adequate insulin dose adjustment. In recent years, continuous glucose measurement has gained accuracy and reliability in outpatient and inpatient settings. The aim of this study was to assess the feasibility and accuracy of real-time continuous glucose monitoring (CGM) in ICU patients after major abdominal surgery. RESEARCH DESIGN AND METHODS: We included patients undergoing pancreatic surgery and solid organ transplantation (liver, pancreas, islets of Langerhans, kidney) requiring an ICU stay after surgery. We used a Dexcom G6 sensor, placed in the infraclavicular region, for real-time CGM. Arterial blood glucose measured by the amperometric principle (ABL 800; Radiometer, Copenhagen, Denmark) served as a reference value and for calibration. Blood glucose was also routinely monitored by a StatStrip bedside glucose meter. Sensor accuracy was assessed by mean absolute relative difference (MARD), bias, modified Bland-Altman plot, and surveillance error grid for paired samples of glucose values from CGM and acid-base analyzer (ABL). RESULTS: We analyzed data from 61 patients and obtained 1,546 paired glucose values from CGM and ABL. Active sensor use was 95.1%. MARD was 9.4%, relative bias was 1.4%, and 92.8% of values fell in zone A, 6.1% fell in zone B, and 1.2% fell in zone C of the surveillance error grid. Median time in range was 78%, with minimum (<1%) time spent in hypoglycemia. StatStrip glucose meter MARD compared with ABL was 5.8%. CONCLUSIONS: Our study shows clinically applicable accuracy and reliability of Dexcom G6 CGM in postoperative ICU patients and a feasible alternative sensor placement site.

Quantification of systemic delivery of substrates for intermediate metabolism during citrate anticoagulation of continuous renal replacement therapy.

BACKGROUND: There are limited data on systemic delivery of metabolic substrates during citrate anticoagulation. The direct citrate measurements are usually not available. METHODS: Patients on 2.2% acid-citrate-dextrose (ACD, n = 41) were compared to a control group on unfractionated heparin (n = 17). All were treated on 1.9-m(2) polysulfone filters. Samples were taken from the central venous catheter, ports pre- and post-filter and from effluent. RESULTS: The gain of citrate in CVVH (n = 18) was not different from CVVHDF (n = 23, p = 0.8). Mean gain of citrate was 25.4 ± 6.4 mmol/h. The systemic loads of lactate (p = 0.12) and glucose (p = 0.23) in CVVH were similar to CVVHDF. Mean inputs of lactate and glucose were 62.9 ± 21.1 and 26.6 ± 10.4 mmol/h, respectively. The mean difference between post- and prefilter unmeasured anions (d-UA) correlated with mean difference of citrate concentrations (p < 0.0001, r(2) = 0.66). The estimated caloric load of the citrate modalities was 5,536 ± 1,385 kJ/ 24 h. CONCLUSIONS: ACD might represent a significant load of metabolic substrates, particularly if used with lactate buffer. Systemic delivery of citrate can be predicted using d-UA in the extracorporeal circuit.