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Background Reflective testing, i.e. interpreting, commenting on and, if necessary, adding tests in order to aid the diagnostic process in a meaningful and efficient manner, is an extra service provided by laboratory medicine. However, there have been no prospective randomized controlled trials investigating the value of reflective testing in patient management. Methods In this trial, primary care patients were randomly allocated to an intervention group, where general practitioners received laboratory tests results as requested as well as add-on test results with interpretative comments where considered appropriate by the laboratory specialist, or to a control group, where general practitioners only received the laboratory test results requested. Patients’ medical records were evaluated with a follow-up period of six months. For both groups, the primary outcome measures, i.e. both intended action and actual management action, were blindly assessed by an independent expert panel as adequate, neutral or inadequate. Results In 226 of the 270 cases (84%), reflective testing was considered to be useful for the patient. In the intervention group ( n = 148), actual management by the general practitioner was scored as adequate ( n = 104; 70%), neutral ( n = 29; 20%) or not adequate ( n = 15; 10%). In the control group ( n = 122), these numbers were 57 (47%), 37 (30%) and 28 (23%). This difference was statistically significant ( P Conclusion This randomized controlled trial showed a positive effect of reflective testing in primary care patients on the adequacy of their management, as documented in medical records.

Objectives The main objective of this study was to evaluate the diagnostic accuracy of two novel biomarkers, calprotectin (CP) and serum amyloid A (SAA), along with the more traditional inflammatory markers C-reactive protein (CRP) and white blood cell count (WBC), in patients suspected of having acute appendicitis (AA). The secondary objective was to compare diagnostic accuracy of these biomarkers with a clinical scoring system and radiologic imaging. Methods A total of 233 patients with suspected AA, presenting to the emergency department (ED) between January 2010 and September 2010, and 52 healthy individuals serving as controls, were included in the study. Blood was drawn and CP and SAA−1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). CRP and WBC concentrations were routinely measured and retrospectively abstracted from the electronic health record, together with physical examination findings and radiologic reports. The Alvarado score was calculated as a clinical scoring system for AA. Final diagnosis of AA was based on histopathologic examination. The Mann-Whitney U-test was used for between-group comparisons. Receiver operating characteristic (ROC) curves were used to measure the diagnostic accuracy for the tests and to determine the best cutoff points. Results Seventy-seven of 233 patients (33%) had proven AA. Median plasma levels for CP and SAA−1 were significantly higher in patients with AA than in those with another final diagnosis (CP, 320.9 ng/mL vs. 212.9 ng/mL; SAA−1, 30 mg/mL vs. 0.6 mg/mL; p 7). Ultrasound (US) had a sensitivity of 84% and a specificity of 94%. Computed tomography (CT) had a sensitivity of 100% and a specificity of 91%. The area under the ROC (95% confidence interval [CI]) was 0.67 (95% CI = 0.60 to 0.74) for CP, 0.76 (95% CI = 0.70 to 0.82) for SAA, 0.71 (95% CI = 0.64 to 0.78) for CRP, and 0.79 (95% CI = 0.73 to 0.85) for WBC. No cutoff points had high enough sensitivity and specificity to accurately diagnose AA. However, a high sensitivity of 97% was shown at 7.5 × 109/L for WBC and 0.375 mg/mL for SAA. Conclusions CP, SAA−1, CRP, and WBC were significantly elevated in patients with AA. None had cutoff points that could accurately discriminate between AA and other pathology in patients with suspected AA. A WBC < 7.5 × 109/L, with a low level of clinical suspicion for AA, can identify a subgroup of patients who may be sent home without further evaluation, but who should have available next-day follow-up. Resumen Evaluacion de la Certeza Diagnostica de Marcadores Plasmaticos para el Diagnostico Precoz en los Pacientes con Sospecha de Apendicitis Aguda Objetivos El principal objetivo de este estudio fue evaluar la certeza diagnostica en los pacientes con sospecha de tener una apendicitis aguda de dos nuevos biomarcadores, la calprotectina (CP) y el amiloide A serico (AAS), junto con los marcadores inflamatorios mas tradicionales, como la proteina C reactiva (PCR) y el numero de leucocitos. El objetivo secundario fue comparar la certeza diagnostica de estos biomarcadores con un sistema de puntuacion clinica y la imagen radiologica. Metodologia Se incluyeron en este estudio 233 pacientes con sospecha de apendicitis que acudieron al servicio de urgencias (SU) entre enero de 2010 y septiembre de 2010, y 52 individuos sanos que sirvieron como controles. Se extrajo sangre y se midio la CP y el AAS mediante un ELISA. La PCR y el numero de leucocitos se midieron de forma rutinaria y se recogieron de forma retrospectiva de las historias clinicas electronicas, junto con los hallazgos de la exploracion fisica y los informes radiologicos. La escala Alvarado (Alvarado score) se calculo como un sistema de puntuacion clinica para la apendicitis aguda. El diagnostico final de apendicitis aguda se baso en el examen histopatologico. Se utilizo el test de la U de Mann-Whitney para la comparacion entre los grupos. Las curvas ROC se utilizaron para medir la certeza diagnostica de las pruebas diagnosticas y para determinar los mejores puntos de corte. Resultados Setenta y siete de 233 pacientes (33%) tuvieron apendicitis aguda con certeza. Las medianas de los niveles plasmaticos de CP y AAS fueron significativamente mas altas en los pacientes con apendicitis aguda que en aquellos con otro diagnostico final (CP 321 ng/mL vs. 213 ng/mL; AAS 30 mg/mL vs. 0,6 mg/mL; p 7). La ecografia tuvo una sensibilidad de un 84% y una especificidad de un 94%. La tomografia computarizada (TC) tuvo una sensibilidad de un 100% y una especificidad de un 91%. La curva ROC (intervalo de confianza 95%) fue de 0,67 (IC 95% = 0,60 a 0,74) para la CP, de 0,76 (IC 95% = 0,70 a 0,82) para la AAS, de 0,71 (IC 95%= 0,64 a 0,78) para la PCR y de 0,79 (IC 95%= 0,73 a 0,85) para los leucocitos. Conclusiones La CP, la AAS, la PCR y el numero de leucocitos estaban significativamente elevados en los pacientes con apendicitis aguda. No hay un punto de corte que pueda discriminar de forma certera entre la apendicitis aguda y otra patologia en los pacientes con sospecha de apendicitis aguda. Un numero de leucocitos

BACKGROUND: Anastomotic leakage is a frequent and life-threatening complication after colorectal surgery. Early recognition of anastomotic leakage is critical to reduce mortality. Because early clinical and radiologic signs of anastomotic leakage are often nonspecific, there is an urgent need for accurate biomarkers. Markers of inflammation and gut damage might be suitable, as these are hallmarks of anastomotic leakage. STUDY DESIGN: In 84 patients undergoing scheduled colorectal surgery with primary anastomosis, plasma samples were collected preoperatively and daily after surgery. Inflammatory markers, C-reactive protein; calprotectin; and interleukin-6, and intestinal damage markers, intestinal fatty acid binding protein; liver fatty acid binding protein; and ileal bile acid binding protein, were measured. Diagnostic accuracy of single markers or combinations of markers was analyzed by receiver operating characteristic curve analysis. RESULTS: Anastomotic leakage developed in 8 patients, clinically diagnosed at median day 6. Calprotectin had best diagnostic accuracy to detect anastomotic leakage postoperatively. Highest diagnostic accuracy was obtained when C-reactive protein and calprotectin were combined at postoperative day 3, yielding sensitivity of 100%, specificity of 89%, positive likelihood ratio = 9.09 (95% CI, 4.34-16), and negative likelihood ratio = 0.00 (95% CI, 0.00-0.89) (p < 0.001). Interestingly, preoperative intestinal fatty acid binding protein levels predicted anastomotic leakage at a cutoff level of 882 pg/mL with sensitivity of 50%, specificity of 100%, positive likelihood ratio = infinite (95% CI, 4.01-infinite), and negative likelihood ratio = 0.50 (95% CI, 0.26-0.98) (p < 0.0001). CONCLUSIONS: Preoperative intestinal fatty acid binding protein measurement can be used for anastomotic leakage risk assessment. In addition, the combination of C-reactive protein and calprotectin has high diagnostic accuracy. Implementation of these markers in daily practice deserves additional investigation.

1.During infusion of [5-15N]glutamine in patients with gastrointestinal cancer we unexpectedly observed a gradual decrease in time of the appearance rate (Ra) of glutamine in plasma. Here we investigate whether the failure to achieve a plateau isotopic enrichment in plasma is, among other factors, due to incomplete equilibration of the glutamine tracer with the large intramuscular free glutamine pool. 2.Plasma and intramuscular glutamine enrichment were measured during 6–11 ;h infusions of L-[5-15N]glutamine and L-[1-13C]glutamine in post-absorptive patients admitted to hospital for elective abdominal surgery. L-[1-13C]Leucine and L-[ring-2H5]phenylalanine were infused to measure the proportion of glutamine appearing in plasma directly due to its release from protein. 3.The glutamine tracer entered muscle, but the rise in intramuscular glutamine enrichment was small, presumably as a result of the enormous size of the intramuscular glutamine pool and the limited speed of entry of glutamine into muscle. In each patient the intramuscular glutamine enrichment was lower than that in plasma (P < 0.001), and both increased with tracer infusion time (P < 0.001), indicating incomplete equilibration of the glutamine tracer. 4.A comparison of the results obtained by the two glutamine tracers indicated that recycling of the nitrogen label contributed to about 15% of the decrease in Ra. 5.There was a gradual reduction in the glutamine release from proteolysis, which contributed to 16–21% of the decline in Ra. 6.We conclude that slow equilibration of the glutamine tracer with the large muscle glutamine pool significantly contributes to the absence of isotopic steady state. Consequently, the appearance rate of glutamine in plasma measured during short tracer infusion periods (hours) considerably overestimates the whole-body glutamine flux.

The study of protein kinetics has entered a new era by the recognition that whole body protein turnover only poorly reflects the true events occurring in several organs and with regard to the multitude of proteins present in the body. It is also increasingly recognized that the simultaneous synthesis and degradation of proteins is important in regulation and adaptation during several metabolic conditions like starvation, feeding, after trauma, and during exercise. Especially important is the recognition that the kinetics of individual proteins may change in opposite directions, thereby leading to fluxes of alpha-amino-nitrogen that serve to adapt to and survive a changing environment. At present, much emphasis is put upon molecular biological regulation. However, it is important that the metabolic processes that occur in the intact organism are still poorly defined. New technology allows the exploration of these processes, which should therefore prompt the initiation of further research in this area.

Background: Determination of leukocyte (WBC) counts in pleural fluid is routinely performed by microscopic examination. In this study, we evaluated the performance of automated (differential) WBC counting in comparison with manual counting. Methods: Pleural fluid samples (n = 45) were obtained from patients undergoing diagnostic thoracocentesis. The manual total WBC count was determined after Samson staining in a Fuchs-Rosenthal hemocytometer; microscopic differential counts were performed on May-Grunwald Giemsa-stained cytospin slides. The Sysmex XE-2100 hematology analyzer was used for automated (differential) WBC counting. The functional detection limit was determined by serial dilution of continuous ambulatory peritoneal dialysis (CAPD) fluid and replicate measurements of each dilution. Results: The automated WBC count (× 106/L) was highly correlated with that of the microscopic reference method (r2 = 0.95; WBC-analyzer = 0.97 x WBC-reference method + 16; n = 45). Good agreement was also observed for the absolute lymphocyte count (r2 = 0.92; WBC-analyzer = 0.99 x WBC-reference method + 32; n = 36), neutrophil count (r2 = 0.94; WBC-analyzer = 0.91 x WBC-reference method + 6; n = 35), and monocyte count (r2 = 0.73; WBC-analyzer = 0.83 x WBC-reference method + 6; n = 38). The functional detection limit for WBCs was calculated at 50 × 106/L (coefficient of variation 20%). Conclusions: With some limitations, total and differential WBC counts in pleural fluid can be reliably determined using the Sysmex XE-2100 instrument.

Background : Nutritional depletion has been related to low glutamine levels in plasma and gut mucosa. This study was set up to investigate the effects of glutamine-enriched total parenteral nutrition on intestinal morphology and permeability. Methods : Twenty-three depleted patients were randomized and after stabilization baseline measurements were performed. Plasma glutamine concentrations, gut morphology (including proliferation and lymphocyte markers) and intestinal permeability were measured. After administration during 8–10 days of a glutamine enriched total parenteral nutrition or an isonitrogenous control solution the measurements were repeated. Results : No significant changes in glutamine concentrations, intestinal permeability, mucosal morphology or gut mucosal inflammation were observed between groups. Conclusions : Glutamine enriched total parenteral nutrition in a depleted patient population does not result in improvements in gut morphology and gut barrier function.