Changes in PUFA and eicosanoid metabolism during/after apnea diving: a prospective single-center study.

Background: The popularity of apneic diving is continually growing. As apnea diving substantially burdens the cardiovascular system, special focus is warranted. Regarding inflammation processes and associated inflammatory-related diseases (e.g., cardiovascular diseases), eicosanoids play an important role. This study aims to investigate polyunsaturated fatty acids (PUFAs) and eicosanoids in voluntary apnea divers, and so to further improve understanding of pathophysiological processes focusing on proinflammatory effects of temporarily hypercapnic hypoxia.. Methods: The concentration of PUFAs and eicosanoids were investigated in EDTA plasma in apnea divers (n=10) before and immediately after apnea, 0.5 hour and four hours later, applying liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Mean age was 41±10 years, and divers performed a mean breath-hold time of 317±111 seconds. PUFAs, eicosanoids and related lipids could be classified in four different kinetical reaction groups following apnea. The first group (e.g., Ω-6 and Ω-3-PUFAs) showed an immediate concentration increase followed by a decrease below baseline four hours after apnea. The second group (e.g., thromboxane B2) showed a slower increase, with its maximum concentration 0.5 hour post-apnea followed by a decrease four hours post-apnea. Group 3 (9- and 13-hydroxyoctadecadienoic acid) is characterized by two concentration increase peaks directly after apnea and four hours afterward compared to baseline. Group 4 (e.g., prostaglandin D2) shows no clear response. Conclusion: Changes in the PUFA metabolism after even a single apnea revealed different kinetics of pro- and anti-inflammatory regulations and changes for oxidative stress levels. Due to the importance of these mediators, apnea diving should be evaluated carefully and be performed only with great caution against the background of cardiovascular diseases and inflammation processes.

Hematologic changes after short term hypoxia in non-elite apnea divers under voluntary dry apnea conditions.

PURPOSE: This study investigated the acute changes in full spectrum differential blood cell count including reticulocytes and immature reticulocytes after a voluntary maximal dry apnea in non-elite divers. Aim of the present study is to obtain information on important regulatory compensation mechanisms and to provide insights into apneic regulatory processes. METHODS: Ten apnea divers performed a voluntary dry mean apnea time of 317 sec [SD ±111 sec]. Differential blood cell count including reticulocytes was measured before and immediately after a single maximal breath-hold. To evaluate kinetics, blood samples were also taken after 30 min and 4 h. Value distributions are presented with dot plots. P-values were calculated using a mixed linear model for time dependency. Four difference values were compared to baseline values with Dunnett's procedure. RESULTS: Significant changes were found in red blood cell parameters for erythrocytes, red cell distribution width, hematocrit, hemoglobin, MCV, reticulocytes and immature reticulocytes, and in white blood cell parameters for leucocytes, lymphocytes, immature granulocytes, monocytes, basophile granulocytes, neutrophil granulocytes and eosinophil granulocytes and for thrombocytes. CONCLUSION: Adaptive mechanisms regarding cell counts in elite apnea divers are not readily transferable to non-elite recreational sportspersons. Divers and physicians should be aware of the limited adaptive performance of humans in the case of extended apnea.

Haematopoietic alterations in neonates with congenital diaphragmatic hernia receiving extracorporeal membrane oxygenation support.

BACKGROUND: Extracorporeal membrane oxygenation procedure (ECMO) has been established in the therapy of respiratory insufficient infants with congenital diaphragmatic hernia. In congenital diaphragmatic hernia newborns, a delay in transfer to an ECMO centre is associated with a sharp increase in mortality. Predictive factors for ECMO support are urgently needed. We evaluated the routine parameters of the first blood withdrawal after birth in congenital diaphragmatic hernia infants, hypothesizing that early signs in bone marrow affecting haematology parameters for early regulation of potentially post birth hypoxia are predictive factors for ECMO support. MATERIALS AND METHODS: In 44 patients born with congenital diaphragmatic hernia, differential blood cell count from the first blood withdrawal after birth was examined. Descriptive statistics included median, 95% confidence intervals, minimum and maximum differentiating ECMO/early mortality vs. no ECMO. Odds ratios with CI were calculated by binary logistic regression analysis. Best predictive markers were further checked in combination with the liver-up situation in two factorial regression models. RESULTS: In our cohort, the survival rate was 77.3% (34/44). While 18 neonates received ECMO support, 26 experienced no ECMO during hospital stay. Odds ratio calculations showed that risk for ECMO support increases with augmenting leukocytes, erythrocytes, haemoglobin, haematocrit, mean cell volume and absolute immature granulocytes. Further, the risk advanced in line with the severity of congenital diaphragmatic hernia assessed by prenatal ultrasound. CONCLUSIONS: We conclude that these parameters are associated with disease severity in congenital diaphragmatic hernia newborns and may be considered potentially predictive biomarkers for the necessity of ECMO support.

Validity of the Manchester Triage System in emergency patients receiving life-saving intervention or acute medical treatment-A prospective observational study in the emergency department.

RATIONALE, AIMS, AND OBJECTIVES: The spectrum of cases seen by emergency departments ranges from minor illnesses or injuries to complex diseases with high mortality. Some patients require life-saving interventions (LSIs) or therapeutic treatment for an acute illness to prevent an expected imminent life-threatening condition immediately upon arrival. No published study has evaluated the validity of the Manchester Triage System (MTS) in the context of immediate LSI or acute emergency treatment (AET). METHODS: The definition of LSI was based on a literature search. AET was defined by an expert panel based on current emergency guidelines and diagnostic guideline recommendations. In a 4-month observation period, an independent external observer documented all executed LSIs or AETs using a checklist. Sensitivity, negative predictive value, likelihood ratio negative (LR-), and accuracy of MTS triage level for the identification of patients receiving an LSI or AET were calculated. RESULTS: In 1762 patients, 40 (2.3%) LSIs and 89 (5.1%) AETs were observed. In the LSI group, sensitivity of MTS was 75.0%, negative predictive value (NPV) was 99.2% (95% CI: 98.7%-99.6%), LR- was 0.303 (95% CI: 0.189-0.487) and accuracy (ACC) was 98.5% (95% CI: 97.8%-98.9%). In the AET group, sensitivity was 82.0%, NPV was 98.9% (95% CI: 98.1%-99.3%), LR- was 0.206 (95% CI: 0.132-0.322), and ACC was 86.5% (95% CI: 84.9%-88.1%). CONCLUSION: The MTS is a valid instrument for a first assessment of emergency patients in critical condition upon arrival.

Thrombolysis in stroke patients: Comparability of point-of-care versus central laboratory international normalized ratio.

BACKGROUND: In acute stroke patients, thrombolysis is one gold standard therapy option within the first four hours after the ischemic event. A contraindication for thrombolysis is an International Normalized Ratio (INR) value >1.7. Since time is brain, rapid and reliable INR results are fundamental. Aim was to compare INR values determined by central laboratory (CL) analyzer and Point-of-Care Testing(POCT)-device and to evaluate the quality of POCT performance in cases of potential therapeutic thrombolysis at a certified stroke unit. METHODS: In 153 patients INR measurements using POCT-devices (HEMOCHRON Signature Elite®) were compared to INR measurements (BCS®XP) performed at the central laboratory. Outlier evaluation was performed regarding the critical thrombolysis cut-off. RESULTS: Overall, we demonstrated a significant correlation (r = 0.809, p<0.0001) between both measurement methods. Mean value of the absolute difference between CL-INR and POCT-INR measurements was 0.23. In 95.4% of these cases, no differences regarding the critical cut-off (INR 1.7) were observed. POCT-INR values tended to be higher than the CL-INR values (p = 0.01). In 4.6% cases, a different value regarding thrombolysis cut-off was found. All patients were >75 years. CONCLUSIONS: POCT-INR measurements based on our POCT concept are suitable to determine INR values in critical stroke patients. Nevertheless, outlier evaluation is mandatory.

Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of value in discriminating benign and malignant cervical diseases. Carcinoembryonic antigen and alpha-fetoprotein distinguished precancerous breast and vulva diseases from healthy controls. These findings show that luminescent oxygen channeling immunoassays-based tumor marker assays provide reliable results in routine diagnostics.

Influence of Apnea-induced Hypoxia on Catecholamine Release and Cardiovascular Dynamics.

Prolonged breath-hold causes complex compensatory mechanisms such as increase in blood pressure, redistribution of blood flow, and bradycardia. We tested whether apnea induces an elevation of catecholamine-concentrations in well-trained apneic divers.11 apneic divers performed maximal dry apnea in a horizontal position. Parameters measured during apnea included blood pressure, ECG, and central, in addition to peripheral hemoglobin oxygenation. Peripheral arterial hemoglobin oxygenation was detected by pulse oximetry, whereas peripheral (abdominal) and central (cerebral) tissue oxygenation was measured by Near Infrared Spectroscopy (NIRS). Exhaled O2 and CO2, plasma norepinephrine and epinephrine concentrations were measured before and after apnea.Averaged apnea time was 247±76 s. Systolic blood pressure increased from 135±13 to 185±25 mmHg. End-expiratory CO2 increased from 29±4 mmHg to 49±6 mmHg. Norepinephrine increased from 623±307 to 1 826±984 pg ml-1 and epinephrine from 78±22 to 143±65 pg ml-1 during apnea. Heart rate reduction was inversely correlated with increased norepinephrine (correlation coefficient -0.844, p=0.001). Central (cerebral) O2 desaturation was time-delayed compared to peripheral O2 desaturation as measured by NIRSabdominal and SpO2.Increased norepinephrine caused by apnea may contribute to blood shift from peripheral tissues to the CNS and thus help to preserve cerebral tissue O2 saturation longer than that of peripheral tissue.

Validity of the Manchester Triage System in patients with sepsis presenting at the ED: a first assessment.

BACKGROUND: The Manchester Triage System (MTS) does not have a specific presentational flow chart for sepsis. The goal of this investigation was to determine adequacy of acuity assignment for patients with sepsis presenting at the ED and triaged using the MTS. MATERIALS AND METHODS: This retrospective analysis included patients >16 presenting to an ED in Bonn, Germany, on the first 12 days of each month between June 2012 and March 2014. Patients were classified into one of three septic groups, or no sepsis. For those with sepsis, adequacy of acuity assignment was based on the criteria of the first consensus conference of the American College of Chest Physicians and Society of Critical Care Medicine, first published in 1992. Adequacy of prioritisation is expressed as sensitivity and likelihood ratio (LR-). RESULTS: Among 20 836 patients evaluated, 801 (3.8%) were septic; of these, 581 (72.5%) had sepsis, 194 (24.2%) had severe sepsis and 26 (3.2%) had severe sepsis with circulation dysfunction. Patients who met the criteria for sepsis were correctly prioritised with a sensitivity of 70.4% (95% CI 66.5 to 74.0). The LR- was 0.628 (95% CI 0.564 to 0.698). Patients with severe sepsis were appropriately prioritised with a sensitivity of 84.5% (95% CI 78.1 to 89.4), and LR- was 0.330 (95% CI 0.243 to 0.450). In the group with severe sepsis and circulation dysfunction, sensitivity of MTS was 61.5% (95% CI 39.3 to 79.8), and LR- was 0.466 (95% CI 0.286 to 0.757). CONCLUSIONS: The MTS has some weaknesses regarding priority levels in emergency patients with septic illness. Overall, target key symptoms (discriminators) which aim at identifying systemic infection and ascertaining vital parameters are insufficiently considered.

Clinical Performance of CEA, CA19-9, CA15-3, CA125 and AFP in Gastrointestinal Cancer Using LOCI™-based Assays.

BACKGROUND/AIM: Few data are available regarding the clinical performance of LOCI™-based tumor marker assays. We investigated the diagnostic power of carcinogenic antigen, carbohydrate antigen 19-9, carbohydrate antigen 15-3, carbohydrate antigen 125 and alpha-fetoprotein for detection of gastrointestinal (GI) cancer. PATIENTS AND METHODS: We analyzed sera from 204 patients (107 with GI cancer, 73 with benign GI diseases and 24 healthy controls) using the Dimension™ Vista1500 analyzer. RESULTS: Levels of biomarkers in healthy controls were in the expected ranges and were only slightly higher in benign GI controls. Established tumor-type-associated markers were elevated in specific cancer types and discriminated well between cancer and benign controls. Best performance was found for CEA in colorectal cancer (area under the curve=0.84, sensitivity=51.7% at 95% specificity vs. benign), CA19-9 in gallbladder/pancreatic cancer (AUC=0.85, sensitivity=60.6%) and AFP in liver cancer (AUC=0.87, sensitivity=68.4%). CONCLUSION: Our study demonstrated the high diagnostic power of well-known biomarkers. LOCI™-based tumor marker assays give reliable results in routine diagnostics.

Comparability of Point-of-Care versus Central Laboratory Hemoglobin Determination in Emergency Patients at a Supra-Maximal Care Hospital.

Fulfilling the requirements of point-of-care testing (POCT) training regarding proper execution of measurements and compliance with internal and external quality control specifications is a great challenge. Our aim was to compare the values of the highly critical parameter hemoglobin (Hb) determined with POCT devices and central laboratory analyzer in the highly vulnerable setting of an emergency department in a supra maximal care hospital to assess the quality of POCT performance. In 2548 patients, Hb measurements using POCT devices (POCT-Hb) were compared with Hb measurements performed at the central laboratory (Hb-ZL). Additionally, sub collectives (WHO anemia classification, patients with Hb <8 g/dl and suprageriatric patients (age >85y.) were analyzed. Overall, the correlation between POCT-Hb and Hb-ZL was highly significant (r = 0.96, p<0.001). Mean difference was -0.44g/dl. POCT-Hb values tended to be higher than Hb-ZL values (t(2547) = 36.1, p<0.001). Standard deviation of the differences was 0.62 g/dl. Only in 26 patients (1%), absolute differences >2.5g/dl occurred. McNemar´s test revealed significant differences regarding anemia diagnosis according to WHO definition for male, female and total patients (♂ p<0.001; ♀ p<0.001, total p<0.001). Hb-ZL resulted significantly more often in anemia diagnosis. In samples with Hb<8g/dl, McNemar´s test yielded no significant difference (p = 0.169). In suprageriatric patients, McNemar´s test revealed significant differences regarding anemia diagnosis according to WHO definition in male, female and total patients (♂ p<0.01; ♀ p = 0.002, total p<0.001). The difference between Hb-ZL and POCT-Hb with Hb<8g/dl was not statistically significant (<8g/dl, p = 1.000). Overall, we found a highly significant correlation between the analyzed hemoglobin concentration measurement methods, i.e. POCT devices and at the central laboratory. The results confirm the successful implementation of the presented POCT concept. Nevertheless some limitations could be identified in anemic patients stressing the importance of carefully examining clinically implausible results.

Evaluation of the appropriate time period between sampling and analyzing for automated urinalysis.

INTRODUCTION: Preanalytical specifications for urinalysis must be strictly adhered to avoid false interpretations. Aim of the present study is to examine whether the preanalytical factor 'time point of analysis' significantly influences stability of urine samples for urine particle and dipstick analysis. MATERIALS AND METHODS: In 321 pathological spontaneous urine samples, urine dipstick (Urisys™2400, Combur-10-Test™strips, Roche Diagnostics, Mannheim, Germany) and particle analysis (UF-1000 i™, Sysmex, Norderstedt, Germany) were performed within 90 min, 120 min and 240 min after urine collection. RESULTS: For urine particle analysis, a significant increase in conductivity (120 vs. 90 min: P < 0.001, 240 vs. 90 min: P < 0.001) and a significant decrease in WBC (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), RBC (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), casts (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001) and epithelial cells (120 vs. 90 min P = 0.610, 240 vs. 90 min P = 0.041) were found. There were no significant changes for bacteria. Regarding urine dipstick analysis, misclassification rates between measurements were significant for pH (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), leukocytes (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), nitrite (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), protein (120 vs. 90 min P < 0.001, 240 vs. 90 min P<0.001), ketone (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), blood (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001), specific gravity (120 vs. 90 min P < 0.001, 240 vs. 90 min P < 0.001) and urobilinogen (120 vs. 90 min, P = 0.031). Misclassification rates were not significant for glucose and bilirubin. CONCLUSION: Most parameters critically depend on the time window between sampling and analysis. Our study stresses the importance of adherence to early time points in urinalysis (within 90 min).

Impact of carbamylation on three different methods, HPLC, capillary electrophoresis and TINIA of measuring HbA1c levels in patients with kidney disease.

AIMS: Aim of this study was to investigate whether established IFCC traceable routine measurements of HbA1c levels in patients with kidney diseases result in comparable and valid results. Additionally, the influence of carbamylation as a marker of uremia on the measurement methods was assessed. METHODS: We compared three different measurement methods (high-performance liquid chromatography (HPLC), capillary electrophoresis and turbidimetric inhibition immunoassay (TINIA)) based on 407 nephrology samples for HbA1c determination with specific analysis of the threshold areas where different HbA1c measurements could result in different diagnoses (diabetes mellitus vs prediabetes and prediabetes vs non-diabetes). Indirectly, a potential effect of carbamylated hemoglobin was assessed based on determination of BUN levels in serum. RESULTS: In nephrological samples, we were able to show that three different measurement methods provide similar results regarding HbA1c in routine diagnostics. Our results show that with BUN concentrations <80 mg/dl and ≥80 mg/dl, similar HbA1c levels were determined, independent of measurement method. CONCLUSION/DISCUSSION: While routine measurements follow IFCC standards, many interfering factors remain which can influence HbA1c determination, e.g. carbamylation of proteins. As kidney disease is the most common complication in patients with diabetes mellitus, interference in the measurement of HbA1c due to carbamylated proteins as markers of uremia must be recognized and if necessary corrected. We found not only a weak influence of carbamylation on all methods of HbA1c determination, but also that, in nephrological samples, the three different measurement methods provided similar results regarding HbA1c in routine diagnostics.