Combined Use of Presepsin and (1,3)-ß-D-glucan as Biomarkers for Diagnosing Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients.

New biomarker panel was developed and validated on 165 critically ill adult patients to enable a more accurate invasive candidiasis (IC) diagnosis. Serum levels of the panfungal biomarker (1,3)-ß-D-glucan (BDG) and the inflammatory biomarkers C-reactive protein, presepsin (PSEP), and procalcitonin (PCT) were correlated with culture-confirmed candidemia or bacteremia in 58 and 107 patients, respectively. The diagnostic utility was evaluated in sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). BDG was the best marker for IC, achieving 96.6% sensitivity, 97.2% specificity, 94.9% PPV, and 98.1% NPV at a cut-off of 200 pg/mL (p ≤ 0.001). PSEP exhibited 100% sensitivity and 100% NPV at a cut-off of 700 pg/mL but had a lower PPV (36.5%) and low specificity (5.6%). Combined use of PSEP and BDG, thus, seems to be the most powerful laboratory approach for diagnosing IC. Furthermore, PSEP was more accurate for 28-day mortality prediction the area under the receiver operating characteristic curve (AUC = 0.74) than PCT (AUC = 0.31; PCT cut-off = 0.5 ng/mL). Finally, serum PSEP levels decreased significantly after only 14 days of echinocandin therapy (p = 0.0012). The probability of IC is almost 100% in critically ill adults with serum BDG and PSEP concentrations > 200 pg/mL and >700 pg/mL, respectively, defining a borderline between non-invasive superficial Candida colonization and IC.

Efficiency of acidemia correction on intermittent versus continuous hemodialysis in acute methanol poisoning.

CONTEXT: Acidemia is a marker of prognosis in methanol poisoning, as well as compounding formate-induced cytotoxicity. Prompt correction of acidemia is a key treatment of methanol toxicity and methods to optimize this are poorly defined. OBJECTIVE: We studied the efficiency of acidemia correction by intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) in a mass outbreak of methanol poisoning. METHODS: The study was designed as observational cohort study. The mean time for an increase of 1 mmol/L HCO3-, 0.01 unit arterial blood pH, and the total time for correction of HCO3- were determined in IHD- and CRRT-treated patients. RESULTS: Data were obtained from 18 patients treated with IHD and 13 patients treated with CRRT. At baseline, CRRT group was more acidemic than IHD group (mean arterial pH 6.79 ± 0.10 versus 7.05 ± 0.10; p = 0.001). No association was found between the rate of acidemia correction and age, weight, serum methanol, lactate, formate, and glucose on admission. The time to HCO3- correction correlated with arterial blood pH (r= -0.511; p = 0.003) and creatinine (r = 0.415; p = 0.020). There was association between the time to HCO3- correction and dialysate/effluent and blood flow rates (r= -0.738; p < 0.001 and r= -0.602; p < 0.001, correspondingly). The mean time for HCO3- to increase by 1 mmol/L was 12 ± 2 min for IHD versus 34 ± 8 min for CRRT (p < 0.001), and the mean time for arterial blood pH to increase 0.01 was 7 ± 1 mins for IHD versus 11 ± 4 min for CRRT (p = 0.024). The mean increase in HCO3- was 5.67 ± 0.90 mmol/L/h for IHD versus 2.17 ± 0.74 mmol/L/h for CRRT (p < 0.001). CONCLUSIONS: Our study supports the superiority of IHD over CRRT in terms of the rate of acidemia correction.

Intermittent hemodialysis is superior to continuous veno-venous hemodialysis/hemodiafiltration to eliminate methanol and formate during treatment for methanol poisoning.

During an outbreak of methanol poisonings in the Czech Republic in 2012, we were able to study methanol and formate elimination half-lives during intermittent hemodialysis (IHD) and continuous veno-venous hemodialysis/hemodiafiltration (CVVHD/HDF) and the relative impact of dialysate and blood flow rates on elimination. Data were obtained from 11 IHD and 13 CVVHD/HDF patients. Serum methanol and formate concentrations were measured by gas chromatography and an enzymatic method. The groups were relatively comparable, but the CVVHD/HDF group was significantly more acidotic (mean pH 6.9 vs. 7.1 IHD). The mean elimination half-life of methanol was 3.7 and formate 1.6 h with IHD, versus 8.1 and 3.6 h, respectively, with CVVHD/HDF (both significant). The 54% greater reduction in methanol and 56% reduction in formate elimination half-life during IHD resulted from the higher blood and dialysate flow rates. Increased blood and dialysate flow on the CVVHD/HDF also increased elimination significantly. Thus, IHD is superior to CVVHD/HDF for more rapid methanol and formate elimination, and if CVVHD/HDF is the only treatment available then elimination is greater with greater blood and dialysate flow rates.

Capillary electrophoresis with contactless conductometric detection for rapid screening of formate in blood serum after methanol intoxication.

A new method for rapid, direct determination of formate in blood serum samples by capillary electrophoresis with contactless conductometric detection is presented. A selective separation of formate was achieved in approximately 1 min using an electrolyte system comprising 10 mM L-histidine, 15 mM glutamic acid and 30 µM cetyltrimethylammonium bromide at pH 4.56. The only sample preparation was dilution (1:100) with deionized water. The limit of detection and limit of quantitation was 2.2 µM and 7.3 µM, respectively, which corresponds to 0.22 mM and 0.73 mM in undiluted blood serum. The method provides a simple and rapid diagnostic test in suspected methanol intoxication cases. The method has been successfully tested on determination of formate in blood of a patient admitted to the hospital under acute methanol intoxication. The peak concentration of formate detected in the patient blood serum was 12.4mM, which is 10- to 100-fold higher than the normal values in healthy population. The developed method presents the fastest test currently available to detect formate in blood samples.