Hepcidin and other indicators of iron status, by alpha-1 acid glycoprotein levels, in a cohort of Mexican infants.

The purpose of this study was to describe the changes in iron status indicators at 6 and 12 months of age, controlling by inflammation by measuring alpha-1 acid glycoprotein (AGP). This longitudinal study included 48 healthy-term singleton infants with birth weight ≥ 2500 g, born in hospitals of the Mexican Institute for Social Security. Complete blood count, ferritin, soluble transferrin receptor (sTfR), hepcidin, and AGP were measured in blood at 6 and 12 months of age. sTfR/ferritin ratio and total body iron (TBI) stores were calculated. Hemoglobin and sTfR/ferritin ratio increased with age, while ferritin and TBI decreased. In infants without inflammation, hepcidin, sTfR, and MVC did not show significant changes from 6 to 12 months of age, while ferritin and TBI decreased. In infants with inflammation, hepcidin, TBI, and ferritin levels increased, while hemoglobin and sTfR/ferritin ratio decreased. MVC and sTfR did not change significantly in the presence or absence of inflammation. Hepcidin concentration correlated positively and significantly with ferritin and TBI stores and showed significant negative correlation with sTfR/ferritin ratio. Our study showed that, in absence of inflammation and ID, during the first year of life, physiological changes occur in hemoglobin and ferritin levels as well as in indicators derived from ferritin and sTfR; in contrast, hepcidin and sTfR did not show significant change. However, hepcidin concentration was lower in infants with ID and was higher when inflammation was present, supporting that infants have a functional hepcidin response to changes in iron stores.

Performance evaluation of 14 specific proteins measurement checked by an External Quality Assessment Scheme.

AIMS OF THE STUDY: To evaluate the state-of-the-art of 14 specific proteins measurement; to evaluate the laboratories' performance and the degree of harmonization in reporting results of participants in the External Quality Assessment Program of the Centre of Biomedical Research (CRB). METHODS: Overall and system-related inter-laboratory analytical variability (mean CVs%) and between-system differences (mean bias%) were evaluated from data of six EQA cycles 2013-2018. Moreover, we evaluated the analytical performance of participants as well as the units used to express proteins results. RESULTS: Overall inter-laboratory variability ranged from 3.8% for haptoglobin (HPT) to 12.5% for α1-antitrypsin (AAT) and decreased for IgA, α2-macroglobulin (A2M) and transferrin (TRF). Mean CVs% were generally higher for Siemens BN and Beckman Immage immunonephelometric systems, but <7.0% for all proteins. Mean bias > 7.0% was observed for BN (IgA, C4, AAT, transthyretin TTR), Siemens Vista (IgA, C4) and Immage (C4), whereas mean bias < -7.0% was found for Immage (AAT), Beckman AU (IgM) and Roche Cobas (C4, TTR, C-reactive protein). The laboratories' performance within the limits ranged from 85.1% of albumin (ALB) to 97.2% of HPT. The census of units employed in 2018, demonstrated that ~ 70% of laboratories still express the results in mg/dL. CONCLUSIONS: Despite a reduction in inter-laboratory variability for some proteins, different analytical systems showed both proportional and constant bias between methods. Units used by participants have not been substantially changed and dL is still largely used. The CRB EQA Program, with its performance data sets, is a valuable resource for laboratories and IVD manufacturers and support the goals of harmonization.

Disposable carbon nanotube scaffold films for fast and reliable assessment of total α1-acid glycoprotein in human serum using adsorptive transfer stripping square wave voltammetry.

Alpha-1-acid glycoprotein (AGP) is a serum glycoprotein whose levels are increased two or three times during disease or injury. This makes it a potential biomarker for inflammatory bowel diseases and sepsis. Consequently, fast, simple, and cheap analytical methods for prognosis, diagnosis, and follow-up of these diseases are demanded. In this work, we propose a simple electrochemical approach based on carbon nanotubes scaffold films (CNSFs) for total AGP determination in serum samples. Firstly, AGP is labeled with an electrochemical tag (osmium(VI) complex), and then the total amount of AGP is quantified by adsorptive transfer stripping square wave voltammetry (AdTSWV). Multi-walled carbon nanotubes scaffold films (MWSFs) yielded the best analytical performance in terms of sensitivity with a good limit of detection of 0.6 mg L-1 for AGP determination in serum samples, in less than 20 min. A simplified AGP calibration and its sequential serum sample analysis strategy with good accuracy (81%) and excellent reproducibility (RSD < 1%) was additionally proposed to meet the point-of-care/needs requirements. Graphical abstract Multi-walled carbon nanotubes scaffold films for total AGP determination on disposable platforms integrating single-point calibration and sequential sample analysis.

Total α1-acid glycoprotein determination in serum samples using disposable screen-printed electrodes and osmium (VI) as electrochemical tag.

Alpha-1-acid glycoprotein (AGP) or Orosomucoid is a serum glycoprotein which belongs to the group of acute phase proteins. It is a potential biomarker for inflammatory bowel diseases. In this sense, there is a need for developing fast and cheap analytical methods for diagnosis, prognosis and follow-up of these diseases. In this work, we propose a simple and cheap electrochemical method for total AGP determination using disposable carbon screen-printed electrodes (SPE) and using a selective acidic precipitation of the rest of proteins. This method avoids the use of biological components, decreasing dramatically the analysis cost. Firstly, AGP is labeled with an electrochemical tag (osmium (VI) complex) and then the total amount of AGP is quantified by adsorptive transfer stripping square wave voltammetry. The method optimized showed a good linear correlation (r = 0.9992) and limit of detection of 1.6mgl-1. The methodology was successfully applied to quantify AGP in a commercial serum sample. This methodology could be useful in clinical diagnosis because of AGP levels increase two or three times when inflammatory processes happen. Moreover, the inherent advantages of SPE technology (low sample consumption, low cost and point of care testing) make this methodology very attractive in this field.

Population pharmacokinetic-pharmacodynamic modeling and model-based prediction of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer.

PURPOSE: Docetaxel is used to treat many cancers, and neutropenia is the dose-limiting factor for its clinical use. A population pharmacokinetic-pharmacodynamic (PK-PD) model was introduced to predict the development of docetaxel-induced neutropenia in Japanese patients with non-small cell lung cancer (NSCLC). METHODS: Forty-seven advanced or recurrent Japanese patients with NSCLC were enrolled. Patients received 50 or 60 mg/m2 docetaxel as monotherapy, and blood samples for a PK analysis were collected up to 24 h after its infusion. Laboratory tests including absolute neutrophil count data and demographic information were used in population PK-PD modeling. The model was built by NONMEM 7.2 with a first-order conditional estimation using an interaction method. Based on the final model, a Monte Carlo simulation was performed to assess the impact of covariates on and the predictability of neutropenia. RESULTS: A three-compartment model was employed to describe PK data, and the PK model adequately described the docetaxel concentrations observed. Serum albumin (ALB) was detected as a covariate of clearance (CL): CL (L/h) = 32.5 × (ALB/3.6)0.965 × (WGHT/70)3/4. In population PK-PD modeling, a modified semi-mechanistic myelosuppression model was applied, and characterization of the time course of neutrophil counts was adequate. The covariate selection indicated that α1-acid glycoprotein (AAG) was a predictor of neutropenia. The model-based simulation also showed that ALB and AAG negatively correlated with the development of neutropenia and that the time course of neutrophil counts was predictable. CONCLUSION: The developed model may facilitate the prediction and care of docetaxel-induced neutropenia.

[The assessment of acute phase proteins as prognostic factors in patients surgically treated for non-small cell lung cancer]. / Ocena wybranych bialek ostrej fazy jako czynników rokowniczych u chorych leczonych chirurgicznie z powodu niedrobnokomórkowego raka pluca.

INTRODUCTION: The aim of the study was to assess quantitative changes of the acute phase protein (APP) serum level in patients with non-small cell lung cancer (NSCLC) who underwent a radical resection. We analysed the correlation between quantitative APP changes and: the survival rate, the histological type of the cancer, TNM stage and grading. MATERIAL AND METHODS: We analysed a group of 46 patients surgically treated for NSCLC from 2003 to 2004. The average age of patients was 61 (45 to 77 years). The most frequent histological types of cancer were: squamous cell lung cancer (24 patients) and adenocarcinoma (17 patients). The majority of them were in stage II B (15 patients) and III A (14 patients). We analysed serum levels of: C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), alpha1-antichymotrypsin (ACT), alpha1-antitrypsin (AT), alpha2-macroglobulin (M), ceruloplasmin (Cp), haptoglobin (Hp), and transferrin (Tf) by means of rocket immunoelectrophoresis by Laurell. RESULTS: The level of AT was significantly higher in patients with adenocarcinoma, as compared to other histological types of cancer. In the case of patients with squamous cell lung cancer, significantly higher M and Cp. We did not find any correlation between the APP level and grading. The levels of five APP: CRP, AGP, ACT, M and Cp were significantly higher in the group of patients with T3 or T4 category, while N1 or N2 status had significantly higher concentrations of AT, CRP and Hp. The multivariate analysis confirmed the influence of the following factors on long-term survival: N stage, histological type of cancer and preoperative serum levels of AGP and Hp. CONCLUSIONS: The serum concentration of some APP may correlate with the more aggressive clinical behavior of lung cancer. The patients with N1 or N2 stage of adenocarcinoma have significantly higher serum level of AT and the preoperative concentration of AGP and Hp correlates with the overall survival. These proteins could serve as prognostic factors in the risk assessment of the cancer recurrence after the surgical management.

Assessment of a prognostic biochemical indicator of nutrition and inflammation for identification of pressure ulcer risk.

BACKGROUND: Pressure ulcers represent a major cost to the healthcare systems of the world but preventative measures are expensive and could be better targeted. Current risk screening mechanisms are often subjective and could be improved. AIMS: To evaluate whether a biochemical assessment tool (Prognostic Inflammatory and Nutritional Index; PINI) based on measurement of albumin, alpha1-acid glycoprotein, C-reactive protein, and prealbumin is of value in estimating the prognosis of patients with pressure ulcers of European Pressure Ulcer Advisory Panel grade 1 and above. METHODS: Serum samples were collected from patients participating in a clinical trial of a pressure ulcer preventing mattress. These were analysed for the markers listed above and the PINI calculated. PINI was then evaluated against patient outcome. RESULTS: A statistically significant difference between PINI values in patients whose pressure ulcers improved and those whose ulcers worsened was found in parametric testing, but significance was not achieved in non-parametric testing. A receiver operating characteristic plot showed the PINI was superior to chance in estimating prognosis. CONCLUSIONS: The PINI appears to offer a potential route to improving pressure ulcer risk estimation and thus allocation of scarce equipment to improve prevention.

Effects of subclinical infection on plasma retinol concentrations and assessment of prevalence of vitamin A deficiency: meta-analysis.

BACKGROUND: Vitamin A deficiency adversely affects child morbidity and survival. This deficiency is estimated by measurement of plasma retinol concentrations, but because plasma retinol is reduced by clinical and subclinical infection, this proxy measure can lead to overestimation. Infection and trauma are accompanied by rises in concentrations of acute-phase proteins in plasma. We aimed to estimate vitamin A deficiency more accurately by measuring changes in plasma retinol and acute-phase proteins associated with subclinical infection or convalescence. METHODS: We analysed data for concentrations of plasma retinol and one or more acute-phase proteins (alpha1-acid-glycoprotein, alpha1-antichymotrypsin, C-reactive protein, or serum amyloid A) from 15 studies of apparently healthy individuals. We generated summary estimates of differences in retinol concentrations for incubation, early, and late convalescent phases of infection between people with none and those with one or more raised acute-phase proteins. We compared these groups in two, three, and four group analyses. We also compared a subgroup of apparently healthy preschool (1-5 years) children with results from all other studies. FINDINGS: For all four proteins, retinol values were much higher in people with normal concentrations of protein, than in individuals with raised concentrations (16% higher for alpha1-antichymotrypsin, 18% for alpha1-acid-glycoprotein, 25% for C-reactive protein, and 32% for serum amyloid A). Estimates of the reduction in plasma retinol for individuals with infection compared with healthy individuals, were 13% (incubation), 24% (early convalescent), and 11% (late convalescent). Estimates of vitamin A deficiency in individuals with no raised acute-phase proteins (healthy group) were much the same as those obtained by adjustment of plasma retinol concentrations in the whole group using acute-phase proteins. INTERPRETATION: We recommend that surveys to estimate vitamin A deficiency should include measurements of serum C-reactive protein and alpha1-acid-glycoprotein concentrations. Information about acute-phase proteins will enable plasma retinol concentrations to be corrected where sub-clinical infection exists, and the healthy sub-group to be identified.

Baseline nutritional assessment in advanced cancer patients receiving palliative chemotherapy.

Depletion of nutritional reserves and significant weight loss can lead to an increased risk of morbidity, reduced chemotherapy response, and shorter survival in patients with cancer. Weight loss and malnutrition are recognized to result from multifactorial processes, which if assessed and managed appropriately may lead to improved treatment outcome. Numerous methodologies are used for the assessment of nutritional status. However, it remains unclear which of these tools is the most appropriate in the setting of cancer chemotherapy. The aim of this study was to investigate the use of various fundamental assessment tools that could be applied to the routine clinical evaluation of nutritional status in patients with advanced solid malignancies before treatment with palliative chemotherapy. We investigated the interrelationships between biochemical indices, anthropometric measures, and a nutritional screening tool, the Mini-Nutritional Assessment, in 73 patients. Many of these measures were highly interrelated, but the baseline history of weight loss in these patients was strongly correlated to the Mini-Nutritional Assessment (MNA) score (P < 0.0005). In turn, baseline weight loss and the MNA score were strongly correlated to serum C-reactive protein (a marker of acute-phase response). In some patients, malnutrition was linked to disease- or treatment-related upper digestive tract morbidity. Testing for the serum concentration of C-reactive protein at baseline may identify a subset of patients for whom a decline in nutritional status is linked to the presence of an active inflammatory response, a recognized precursor of cachexia

Resting energy expenditure before and after surgical resection of gut lesions in pediatric Crohn's disease.

In pediatric Crohn's disease (CD), resection of gut lesions is necessary to remove stenoses and when frequent relapses occur despite nutritional support and medical treatment. After surgery, improved nutritional status and accelerated growth usually follow increased nutritional intake and lower doses of steroids. The aim of this study was to compare energy balance before and after surgery while nutritional intake and steroid therapy were unchanged. Eleven patients, aged 14.5 +/- 2.5 years and with mildly active CD, were explored 1 week before and 1 month after gut resection for stenosis (n = 7) and medical treatment failure (n = 4). Eleven matched children participated in the study as controls. Disease activity was assessed by the Pediatric Crohn's Disease Activity Index and serum orosomucoid concentration. Resting energy expenditure (REE) was measured by indirect calorimetry, and fat-free body mass (FFM) was measured by anthropometry. The patients' mean REE decreased from 46.6 +/- 10.5 kcal/kg FFM/day before surgery to 42.6 +/- 10.3 kcal/kg FFM/day after surgery, while the controls' mean REE was 39 +/- 7 kcal/kg FFM/day (analysis of variance, p = 0.02). After surgery, body weights were not significantly different, but the mean protein oxidation rate was reduced and arm muscle area was increased. Changes in REE per kilogram of FFM per day were not correlated with changes in orosomucoid serum concentrations (r2 = 0.35; p = 0.4). In conclusion, in children with mildly active CD, while nutritional intake and steroid therapy were maintained at preoperative levels, a significant decrease in REE and improved nitrogen utilisation were observed 1 month after resection of the CD gut lesion. This finding suggests better use of energy substrates when CD lesions are removed.

Usefulness of serum ferritin levels in the assessment of iron status in non-pregnant Zairean women of childbearing age.

We studied the usefulness of serum ferritin for the assessment of iron deficiency (ID) or ID anaemia (IDA) of 186 lactating and 27 non-lactating Zairean women (15-45 years old). Haemoglobin (Hb), serum iron (SI), total iron binding capacity (TIBC), and transferrin saturation (TS) were also measured. Participants were recruited in rural Bas-Zaire State in the summers of 1986 and 1989. Serum ferritin ranged from 10 to 360 micrograms l-1 (median 62 micrograms l-1) in lactating women and from 14.2 to 120 micrograms l-1 (median 40 micrograms l-1) in non-lactating women. While mean levels of serum ferritin and TS were within the normal range in both groups of women, those of Hb were below normal (< 12 g dl-1), partly due to inflammation. The prevalence of anaemia was 66% in lactating women and 70% in non-lactating women, and did not change with time. It was higher in women with inflammation than in those without inflammation. Although ID (ferritin < 12 micrograms l-1) was almost absent, after raising the cut-off point of ferritin to 50 micrograms l-1 in women with inflammation, it was present in 28.8% of lactating women and 52% of non-lactating women. While the prevalence of ID assessed by serum ferritin was significantly higher in lactating women studied in 1989 (40.5%) than in those studied in 1986 (13.5%), it was similar in both groups of non-lactating women. ID defined by TS < 16% was present in 41% of lactating women and 21% of non-lactating women. In the presence as well as absence of inflammation, the use of TS identified a higher percentage of lactating women with either ID or IDA than did the use of serum ferritin. We conclude that, in the studied population, unless inflammation is taken into consideration, serum ferritin has a limited value in the diagnosis of ID.

PIP: This cross-sectional study involved 213 healthy Zairian women, 15-45 years old, 186 lactating and 27 nonpregnant, nonlactating women and studied the usefulness of serum ferritin levels for the assessment of iron deficiency (ID) or ID anaemia (IDA). Hemoglobin (Hb), serum iron (SI), total iron binding capacity (TIBC), and transferrin saturation (TS) were also measured. The median parity of lactating women was three, and that of nonlactating women was two. They were recruited at the Nsundi Lutete Hospital (Bas-Zaire State) during August and September of 1986 and 1989. Serum ferritin ranged from 10 to 360 mcg 1-1 (median 62 mcg 1-1) in lactating women and from 14.2 to 120 mcg 1-l (median 40 mcg 1-l) in nonlactating women. While mean levels of serum ferritin and TS were within the normal range in both groups of women, those of Hb were below normal ( 12 g dl-1), partly owing to inflammation. The prevalence of anemia was 66% in lactating women and 70% in nonlactating women, and did not change with time. It was higher in women with inflammation than in those without inflammation. Although ID (ferritin 12 mcg 1-1 ) was almost absent, after raising the cut-off point of ferritin to 50 mcg 1-1 in women with inflammation, it was present in 28.8% of lactating women and 52% of nonlactating women. While the prevalence of ID assessed by serum ferritin was significantly higher in lactating women studied in 1989 (40.5%) than in those studied in 1986 (13.5%), it was similar in both groups of nonlactating women. ID defined by TS 16% was present in 41% of lactating women and 21% of nonlactating women. In the presence as well as absence of inflammation, the use of TS identified a higher percentage of lactating women with either ID or IDA than did the use of serum ferritin. In the studied population, unless inflammation is taken into consideration, serum ferritin has a limited value in the diagnosis of ID.

Prospective assessment of the role of five tumour markers in breast cancer.

Retrospective analysis previously identified significant elevation of five tumour markers, carcinoembryonic antigen (CEA), ferritin, orosomucoid. C-reactive protein and erythrocyte sedimentation rate (ESR), in patients with systemic breast cancer and showed that changes in each of these markers individually correlated significantly with therapeutic response. In this study we have prospectively tested these findings. None of the five markers was significantly elevated in primary breast cancer compared to normal control or benign breast disease groups. They therefore appear to have no role either in screening or in the differential diagnosis of breast cancer. There was a significant elevation of all five markers in patients with systemic breast cancer (P less than 0.0001: analysis of variance) but sequential changes in CEA and ESR only correlated significantly with the UICC-assessed response. Prospective confirmation of the correlation between changes in serum CEA and ESR provides the basis for using these markers in the assessment of response to therapy in patients with systemic breast cancer.

Is basic red cell ferritin a more specific indicator than serum ferritin in the assessment of iron stores in the elderly?

Iron status was evaluated in 103 elderly institutionalized individuals using haemoglobin concentration, red cell indices, serum iron, serum transferrin, serum ferritin and basic red cell ferritin. Inflammatory processes were identified by measuring concentrations of orosomucoid and C-reactive protein in serum and leukocyte counts. Anaemia was present in 16.5% of the individuals. No serum ferritin values were in the range of depleted iron stores; however 6% of the elderly individuals presented basic red cell ferritin less than 3 attog/cell (3 x 10(-18) g/cell). Serum ferritin was positively correlated with markers of inflammation. Basic red cell ferritin measurement was not influenced by inflammation and may provide a reliable indicator of iron status in the elderly.

An objective biochemical assessment of therapeutic response in metastatic breast cancer: a study with external review of clinical data.

A series of tumour related markers have been examined in 179 patients receiving primary endocrine therapy for metastatic breast cancer. Significant correlations between therapeutic response (UICC criteria after 6 months of treatment) and appropriate alterations in serum concentrations of carcinoembryonic antigen, ferritin, c-reactive protein, orosomucoid and the erythrocyte sedimentation rate, have been observed when changes in these markers were examined only at high serum concentrations. By combining these five markers a 'therapeutic index' of response has been devised which can be employed at an early stage of treatment in more than 90% of patients, giving an overall sensitivity/specificity of 90%/78% for therapeutic response or disease stabilisation over a 6-month period. The design of an objective measurement of response, which is easy to perform, has the potential to replace the existing, largely subjective. UICC criteria for retrospective judgement of response, and may also be used to direct systemic endocrine therapy.

Value of serum transthyretin measurements in the assessment of marginal protein-energy malnutrition in rats.

The influence of a wide range of protein and/or energy intakes on the serum level of rat transthyretin was studied. Young and adult rats were fed ad libitum diets containing 18, 9, 6, 4 and 0.5% protein (wt/wt) or were fed a control diet in restricted amounts. The transthyretin level was lower in young rats and was normal or slightly higher in adult rats fed low protein diets than in those fed the 18% protein diet. It was decreased with decreasing energy intake in all energy-restricted rats. Moderate energy restriction in rats fed equivalent amounts of protein also lowered the transthyretin level. Rats with similar body weights and similar protein intakes showed marked differences in serum transthyretin level, depending on the amount of energy consumed. Serum transthyretin changes were discussed in relation to the level of transthyretin in cerebrospinal fluid and to the serum concentration of albumin, transferrin and thyroid hormones. The results show that serum transthyretin is more closely related to the protein and energy intakes than to the protein and energy content of the diet. Our results indicate that serum transthyretin measurement is a reliable marker in the detection of early moderate and severe protein-energy restriction.

Laboratory assessment of disease activity in childhood Crohn's disease and ulcerative colitis.

The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum orosomucoid were measured in children with Crohn's disease and ulcerative colitis in various states of disease activity. Results were matched with a clinical assessment to determine the correlation between laboratory test values and disease activity. Regression analysis showed that serum orosomucoid reflected disease activity better than ESR in both diseases. Orosomucoid but not ESR discriminated between disease in remission and mild disease in ulcerative colitis. No test invariably predicted presence or absence of active disease. Orosomucoid and ESR were complementary, but CRP was of no additional value. The usefulness of orosomucoid and ESR as objective measures of inflammatory activity was not masked by corticosteroid medication.

Assessment of appropriate laboratory measurements to reflect the degree of activity of ulcerative colitis.

Eleven laboratory parameters were compared with the clinical grading of disease activity in 44 patients with ulcerative colitis, using multiple stepwise regression analysis to identify which measurements significantly reflect the severity of the disease. Only 2 parameters, serum orosomucoid and haematocrit showed significant correlation with clinical status. It is suggested that in the method of assessing disease activity proposed by Truelove and Witts the haemoglobin, which in this study was found to have no value, could be replaced by an equally simple test, the haematocrit. Comparisons are made between the relative usefulness of these parameters in ulcerative colitis and Crohn's disease.

Assessment of appropriate laboratory measurements to supplement the Crohn's disease activity index.

The ability of 11 laboratory parameters to reflect the degree of activity of Crohn's disease, using a clinical index as reference point was compared by means of multiple stepwise regression analysis. Activity was best defined in decreasing order by orosomucoid, sedimentation rate, C reactive protein, alpha-1-antitrypsin, albumin, haematocrit, IgM, circulating immune complexes, serum iron, IgG, and IgA. The haematocrit, the only laboratory measurement in the Crohn's disease activity index developed by the National Cooperative Study Group in the USA, is less discriminant than acute phase reactants. Only three parameters-namely, orosomucoid, sedimentation rate, and C reactive protein-have a significant weight and should be complementary to a simple clinical index.