Diagnostic and prognostic value of serum Cys-C, retinol-binding protein, and ischemia-modified albumin in patients with coronary heart disease: A diagnostic accuracy study.

The use of 3 biomarkers - cystatin-C (Cys-C), retinol-binding protein (RBP), and ischemia-modified albumin (IMA) - for the clinical classification and outcome of coronary heart disease (CHD) has not been adequately evaluated. We explored the serum levels of these 3 markers and evaluated their diagnostic and prognostic values in patients with CHD. This retrospective case-control study, conducted between June 2017 and June 2018, included 201 patients with CHD hospitalized at the Henan Provincial People's Hospital and 127 healthy individuals from Henan Provincial People's Hospital as controls. Cys-C, RBP, IMA levels, and other laboratory parameters in the 2 groups were determined, and patient outcomes were analyzed. Cys-C, RBP, and IMA levels were higher in the case group than in the control group (P < .05). Logistic regression analysis confirmed that these 3 biomarkers were independent risk factors for CHD. Each indicator has clinical significance in the diagnosis and prognosis of CHD, with RBP being the most significant. The AUC value for CHD detection using a combination of the 3 indicators was 0.783, and the sensitivity and specificity values were 78% and 74.6%, respectively. Simultaneous detection of Cys-C, RBP, and IMA could be an optimal method for early diagnosis and prognosis of CHD.

Reappraisal of serum retinol-binding protein as a surrogate marker for retinol and discovery of a novel retinol estimation formula.

BACKGROUND & AIMS: Serum retinol (ROH) is commonly used for population level assessment of vitamin A status. High-performance liquid chromatography (HPLC) is considered most accurate method for measuring ROH. However, with the technical difficulty of using HPLC for routine assays, serum retinol-binding protein (RBP) measured by immunological assays is expected to be a surrogate marker for ROH, with reports of a close correlation between serum RBP and ROH. Nevertheless, RBP is not commonly tested to assess vitamin A status with concerns over RBP alterations under various physiopathological conditions. Thus, we reappraised the extent to which RBP could be used as a surrogate marker in representative disorders that alter serum RBP levels. As a related marker, diagnostic utility of transthyretin (TTR) was also evaluated. METHODS: To evaluate the reliability of ROH and RBP assays, specimen stability was assessed in terms of (1) storage at 25, 4, -20, and -80 °C for 1-28 days, (2) five-cycle freeze-thawing, and (3) fluorescent light exposure for 1-14 days. Sources of variation (sex, age, body mass index [BMI], and drinking habits) and reference intervals for ROH, RBP, and TTR were determined in 617 well-defined healthy individuals. To investigate the influence of disorders that affect serum RBP, patients with five diagnostic groups were enrolled: 26 with chronic kidney disease (CKD); 13 with various malignancies in advanced stages (AdM), 12 with acute bacterial infections (ABI), 6 with liver cirrhosis (LC), and 26 with simple obesity (BMI ≥ 27 kg/m2). RESULTS: The stability of RBP and ROH in serum was confirmed under all conditions. In healthy individuals, serum ROH, RBP, and TTR were appreciably high in males with a slight increase in proportion to age and BMI. The major-axis regression line between RBP (x) and ROH (y) in healthy individuals was y = x, with a correlation coefficient of 0.986. In the LC, AdM, and ABI groups, similar strong correlations were observed; however, the regression lines were shifted slightly rightward from the healthy group line, indicating a positive bias in estimating ROH. Interestingly, the same analyses between TTR and ROH revealed similar strong linear relationships in all groups; however, the regression line of each group showed a leftward (opposite) shift from the healthy group line. Based on these observations, we developed a novel regression model composed of RBP and TTR, which gave much improved accuracy in estimating ROH, even under these pathological conditions. CONCLUSIONS: The perfect RBP-ROH correlation in healthy individuals indicates the utility of RPB as a surrogate marker for ROH. Nevertheless, under RBP-altered conditions, a slight overestimation of ROH is inevitable. However, when the TTR was tested together, the bias can be corrected almost perfectly using the novel ROH estimation formula comprising RBP and TTR.

Predictive value of serum retinol binding protein in severity and complications of acute pancreatitis: a retrospective cohort study.

OBJECTIVES: Retinol binding protein (RBP) is associated with an increased risk of insulin resistance, metabolic syndrome, atherosclerosis and hypertension. This study aimed to evaluate serum RBP levels in patients with acute pancreatitis (AP). METHODS: The study included 1,871 AP patients, including 1,411 with mild AP (MAP), 244 with moderately severe AP (MSAP), and 186 with severe AP (SAP). Retrospective analysis was conducted on RBP concentrations and other clinical data of AP patients. RESULTS: AP patients were subgrouped by RBP level into low RBP (LRBP), normal RBP (NRBP), and high RBP (HRBP) groups. The LRBP group showed a significantly higher proportion of SAP patients than NRBP and HRBP groups. Additionally, the LRBP group had the highest BISAP and CTSI scores among the three groups; WBC and CRP levels in the NRBP group were significantly lower than those in the LRBP and HRBP groups. RBP was better at predicting acute necrotic collection (ANC) than other local complications, with an area under the curve (AUC) of 0.821. RBP was also an independent risk factor for acute lung injury (ALI) and ANC in AP patients. The AUC of RBP for predicting ALI was 0.829, with 30.45 mg/L as the optimal cutoff value, and the sensitivity and specificity were 59.70% and 96.50%, respectively. The AUC of RBP for predicting ANC was 0.821, with 28.35 mg/L as the optimal cutoff value, and the sensitivity and specificity were 61.20% and 95.50%, respectively. CONCLUSIONS: Serum RBP had predictive value for AP severity, local and systemic complications.

The level of serum retinol-binding protein is associated with diabetic mild cognitive impairment.

BACKGROUND: Several studies have shown that retinol-binding protein (RBP) is linked to diabetes and neurodegenerative diseases. However, no studies have elucidated the relationship between RBP and diabetic cognitive disorders. OBJECTIVE: To determine whether the change characteristics of serum RBP are associated with alterations in cognitive functioning in type 2 diabetes mellitus (T2DM). METHODS: In this study, 252 patients with T2DM and 34 people as healthy controls were included. According to the Montreal Cognitive Assessment (MoCA), the diabetic subjects were divided into the mild cognitive impairment (MCI) group and the Non-MCI group. Demographic characteristics and clinical indicators as well as serum RBP levels were analyzed. RESULTS: The serum RBP levels in the MCI group were lower compared with the Non-MCI group (P = 0.02). The level of RBP was higher in the diabetes without MCI group than in the healthy control (P < 0.001). Serum RBP levels were positively correlated with MoCA scores (r = 0.178, P = 0.003). Binary Logistic regression model analysis showed that low RBP [odds ratio (OR) = 0.936], old age (OR = 1.074), high fasting blood glucose (OR = 1.164), and low fasting C-peptide (OR = 0.722) may be independent risk factors for diabetic MCI. The ROC curve of serum RBP for predicting diabetic MCI showed that the area under the curve was 0.630. CONCLUSIONS: Our study revealed an association between serum RBP and diabetic MCI. Serum RBP levels in diabetic MCI are lower and correlated with cognitive function.

Optimization of the extract from flower of Citrus aurantium L. var. amara Engl. and its inhibition of lipid accumulation.

Flower of Citrus aurantium L. var. amara Engl. (CAVA) has been confirmed to have promising anti-obesity effects. However, the regulation of alkaloid extracts from flower of CAVA (Al) on lipid metabolism remain unknown. In this study, Al was optimized by ultrasound-assisted extraction using response surface methodology. The optimal conditions were ultrasonic time 72 min, ethanol concentration 78% and liquid/solid ratio 30 ml/g with the maximum alkaloid yield 5.66%. LC-MS assay indicated that the alkaloid compounds were enriched in Al after optimization. Nine alkaloid compounds were identified in Al by LC-MS assay and stachydrine, caffeine and cathine appeared as the major alkaloid compounds. Bioactivity assay showed that Al treatment significantly increased superoxide dismutase (SOD) activity, and reduced malonaldehyde (MDA) and reactive oxygen species (ROS) levels. Al administration also reversed oleic acid-induced hepatic steatosis in Hep G2 cells by inhibiting the expression of lipogenesis-signaling genes including fatty acid synthase (FAS), peroxisome proliferator-activated receptor subtype γ (PPARγ), uncoupling protein 2 (UCP2), and retinol binding protein (RBP4). However, OA-induced reduction of lipolysis-related gene carnitine palmitoyl transferase 1A (CPT1A) in Hep G2 cells was not improved by Al supplementation. Moreover, the increased SOD activity and decreased MDA and ROS contents were also observed in Caenorhabditis elegans by Al addition. Al intervention exhibited the ability to inhibit lipid accumulation in C. elegans by suppressing expression of lipid metabolism-related genes. These results suggested that the alkaloid extracts from the flower of CAVA showed great potential to regulate lipid metabolism. PRACTICAL APPLICATIONS: The extraction of alkaloid extracts from the flower of CAVA was optimized with a maximum yield of 5.66%. The regulatory effects and mechanisms of Al on lipid metabolism of Hep G2 cells and Caenorhabditis elegans were also investigated. More clinical studies are required to evaluate the potential of using alkaloids from the flower of CAVA as therapeutic agents against lipid metabolic disorders.

Blood retinol and retinol-binding protein concentrations are associated with diabetes: a systematic review and meta-analysis of observational studies.

PURPOSE: The associations between blood retinol, retinol-binding protein (RBP) concentrations and diabetes mellitus were inconsistent in literature. The objective is to investigate these associations by a systematic review and meta-analysis and provide basis for clinical intervention. METHODS: PubMed, Web of science, and Cochrane databases were searched from the beginning to July 1, 2021. A total of 13 studies on retinol and 31 studies on RBP are included in the current meta-analysis. RESULTS: The blood retinol concentration was significantly lower in the type I diabetes mellitus (T1DM) [standardized mean difference (SMD) (95% CI): - 0.59 (- 0.81, - 0.37), P < 0.01] and gestational diabetes mellitus (GDM) patients [SMD (95% CI): - 0.54 (- 0.87, - 0.20), P < 0.01] than in the controls. However, the difference was not significant between the type II diabetes mellitus (T2DM) patients and the controls. The RBP concentration was significantly higher in the diabetic patients than in the controls [SMD (95% CI): 0.24 (0.12, 0.35), P < 0.01]. Particularly, the RBP concentration was significantly higher in the T2DM and GDM patients. CONCLUSION: The blood retinol concentration was negatively associated with T1DM and GDM, while the blood RBP concentration was positively associated with T2DM and GDM. Future work should use a more sensitive retinol measurement method like retinol isotope dilution method to confirm whether blood retinol concentration differs between the diabetes patients and the controls.

Evaluation of Hemoglobin Cutoff Levels to Define Anemia Among Healthy Individuals.

Importance: Anemia, defined as low hemoglobin (Hb) concentration insufficient to meet an individual's physiological needs, is the most common blood condition worldwide. Objective: To evaluate the current World Health Organization (WHO) Hb cutoffs for defining anemia among persons who are apparently healthy and to assess threshold validity with a biomarker of tissue iron deficiency and physiological indicator of erythropoiesis (soluble transferrin receptor [sTfR]) using multinational data. Design, Setting, and Participants: In this cross-sectional study, data were collected and evaluated from 30 household, population-based nutrition surveys of preschool children aged 6 to 59 months and nonpregnant women aged 15 to 49 years during 2005 to 2016 across 25 countries. Data analysis was performed from March 2020 to April 2021. Exposure: Anemia defined according to WHO Hb cutoffs. Main Outcomes and Measures: To define the healthy population, persons with iron deficiency (ferritin <12 ng/mL for children or <15 ng/mL for women), vitamin A deficiency (retinol-binding protein or retinol <20.1 µg/dL), inflammation (C-reactive protein >0.5 mg/dL or α-1-acid glycoprotein >1 g/L), or known malaria were excluded. Survey-specific, pooled Hb fifth percentile cutoffs were estimated. Among individuals with Hb and sTfR data, Hb-for-sTfR curve analysis was conducted to identify Hb inflection points that reflect tissue iron deficiency and increased erythropoiesis induced by anemia. Results: A total of 79 950 individuals were included in the original surveys. The final healthy sample was 13 445 children (39.9% of the original sample of 33 699 children; 6750 boys [50.2%]; mean [SD] age 32.9 [16.0] months) and 25 880 women (56.0% of the original sample of 46 251 women; mean [SD] age, 31.0 [9.5] years). Survey-specific Hb fifth percentile among children ranged from 7.90 g/dL (95% CI, 7.54-8.26 g/dL in Pakistan) to 11.23 g/dL (95% CI, 11.14-11.33 g/dL in the US), and among women from 8.83 g/dL (95% CI, 7.77-9.88 g/dL in Gujarat, India) to 12.09 g/dL (95% CI, 12.00-12.17 g/dL in the US). Intersurvey variance around the Hb fifth percentile was low (3.5% for women and 3.6% for children). Pooled fifth percentile estimates were 9.65 g/dL (95% CI, 9.26-10.04 g/dL) for children and 10.81 g/dL (95% CI, 10.35-11.27 g/dL) for women. The Hb-for-sTfR curve demonstrated curvilinear associations with sTfR inflection points occurring at Hb of 9.61 g/dL (95% CI, 9.55-9.67 g/dL) among children and 11.01 g/dL (95% CI, 10.95-11.09 g/dL) among women. Conclusions and Relevance: Current WHO cutoffs to define anemia are higher than the pooled fifth percentile of Hb among persons who are outwardly healthy and from nearly all survey-specific estimates. The lower proposed Hb cutoffs are statistically significant but also reflect compensatory increased erythropoiesis. More studies based on clinical outcomes could further confirm the validity of these Hb cutoffs for anemia.

Retinol-binding protein 4 and plasminogen activator inhibitor-1 as potential prognostic biomarkers of non-allergic asthma caused by obesity in adolescents

Background: Non-allergic asthma caused by obesity is a complication of the low-grade chronic inflammation inherent in obesity. Consequently, the serum concentrations of adipokines such as retinol-binding protein 4 (RBP4) and plasminogen activator inhibitor-1 (PAI-1) increase. No gold standard molecule for the prediction of non-allergic asthma among obese patients has been identified. Objective: To evaluate RBP4 and PAI-1 as prognostic biomarkers of non-allergic asthma caused by obesity. Methods: A cross-sectional study between four groups of adolescents: (1) healthy (n = 35), (2) allergic asthma without obesity (n = 28), (3) obesity without asthma (n = 33), and (4) non-allergic asthma with obesity (n = 18). Results: RBP4 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (39.2 ng/mL [95% confidence interval (CI): 23.8–76.0] vs. 23.5 ng/mL [95% CI: 3.2–33.5], p < 0.01), and PAI-1 was higher in the non-allergic asthma with obesity group than in the obesity without asthma group (21.9 ng/mL [95% CI: 15.7–26.5] vs. 15.9 ng/mL [95% CI: 9.4–18.2], p < 0.05). Receiver operating characteristic (ROC) curve analysis demonstrated that the serum RBP4 cut-off value was >42.78 ng/mL, with an area under the ROC curve (AUC) of 0.741 (95% CI: 0.599–0.853, p = 0.001), considered acceptable. The PAI-1 cut-off value was >12.0 ng/mL, with an AUC of 0.699 (95% CI: 0.554–0.819, p = 0.008), considered fair Conclusions: RBP4 may be useful to predict non-allergic asthma among obese adolescents in clinical practice (AU)

Re-Defining the Population-Specific Cut-Off Mark for Vitamin A Deficiency in Pre-School Children of Malawi.

Retinol Binding Protein (RBP) is responsible for the transport of serum retinol (SR) to target tissue in the body. Since RBP is relatively easy and cheap to measure, it is widely used in national Micronutrient Surveys (MNS) as a proxy for SR to determine vitamin A status. By regressing RBP concentration against SR concentration measured in a subset of the survey population, one can define a population-specific threshold concentration of RBP that indicates vitamin A deficiency (VAD). However, the relationship between RBP and SR concentrations is affected by various factors including inflammation. This study, therefore, aimed to re-define the population-specific cut-off for VAD by examining the influence of inflammation on RBP and SR, among pre-school children (PSC) from the 2015-16 Malawi MNS. The initial association between RBP and SR concentrations was poor, and this remained the case despite applying various methods to correct for inflammation. The World Health Organization (WHO) recommends the threshold of 0.7 µmol/L to define VAD for SR concentrations. Applying this threshold to the RBP concentrations gave a VAD prevalence of 24%, which reduced to 10% after inflammation adjustments following methods developed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA). Further research is required to identify why SR and RBP were poorly associated in this population. Future MNS will need to account for the effect of inflammation on RBP to measure the prevalence of VAD in Malawi.

Vitamin A deficiency has declined in Malawi, but with evidence of elevated vitamin A in children.

BACKGROUND: Reduction of vitamin A deficiency (VAD) in Malawi coincided with introduction of vitamin A-fortified staple foods, alongside continued biannual high-dose vitamin A supplementation (VAS). OBJECTIVE: We describe coverage of vitamin A interventions and vitamin A status in the 2015-2016 Malawi Micronutrient Survey. METHODS: Food samples and biospecimens were collected within a representative household survey across 105 clusters. Retinol was measured using ultraviolet excitation fluorescence (sugar) and photometric determination (oil). Preschool children (PSC, aged 6-59 mo, n = 1102), school-age children (SAC, aged 5-14 y, n = 758), nonpregnant women (n = 752), and men (n = 219) were initially assessed for vitamin A status using retinol binding protein (RBP) and modified relative dose response (MRDR). Randomly selected fasted MRDR participants (n = 247) and nonfasted women and children (n = 293) were later assessed for serum retinol, retinyl esters, and carotenoids. Analyses accounted for complex survey design. RESULTS: We tested sugar and oil samples from 71.8% and 70.5% of the households (n = 2,112), respectively. All of the oil samples and all but one of the sugar samples had detectable vitamin A. National mean retinol sugar and oil contents were 6.1 ± 0.7 mg/kg and 6.6 ± 1.4 mg/kg, respectively. Receipt of VAS in the previous 6 mo was reported by 68.0% of PSC. VAD prevalence (RBP equivalent to <0.7µmol retinol/L) was 3.6% in PSC, and <1% in other groups. One woman and no children had MRDR ≥0.060 indicating VAD. Among fasted PSC and SAC, 18.0% (95% CI: 6.4, 29.6) and 18.8% (7.2, 30.5) had >5% of total serum vitamin A as retinyl esters, and 1.7% (0.0, 4.1) and 4.9% (0.0, 10.2) had >10% of total serum vitamin A as retinyl esters. Serum carotenoids indicated recent intake of vitamin A-rich fruits and vegetables. CONCLUSIONS: Near elimination of VAD in Malawi is a public health success story, but elevated levels of vitamin A among children suggests that vitamin A interventions may need modification.

Comparative evaluation of methods to determine intra-individual reference ranges in nutrition support team (NST)-related tests.

BACKGROUND: The intra-individual reference range is generally narrower than the commonly used reference range. Consequently, close monitoring of changes in the laboratory test results of individuals based on the inter-individual reference range remains challenging. METHODS: We examined the determination of individual reference ranges using four indicators of nutritional conditions: transferrin (TRF), albumin (ALB), retinol-binding protein (RBP), and transthyretin (TTR). The subjects comprised 20 healthy individuals and blood samples were collected and tested five times at 2-week intervals. We used the measurement results for the four indicators and examined individual reference ranges using four methods, including calculation methods based on the reference change value and Bayesian inference. RESULTS: The resulting intra-individual reference ranges were narrower than the currently used inter-individual reference range for all measurements using four methods. Furthermore, the intra-individual coefficient of variation [CV (intra)] was smaller than the inter-individual coefficient of variation [CV (inter)] for TRF, RBP, and TTR for all 20 subjects. The means CV (intra) for the four indicators were also lower than the corresponding CV (inter). CONCLUSIONS: The intra-individual reference range can be used to validate the standard deviation and coefficient of variation for currently used indicators. Moreover, Bayesian methods are speculated to be the most versatile.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

Feasibility and efficacy of home rectal irrigation in neonates and early infancy with Hirschsprung disease.

PURPOSE: A single-stage pull-through (SSPT) is the most commonly performed procedure for Hirschsprung disease (HSCR) and has been shown to be better than multi-stage procedures. However, performing a SSPT in the neonatal period or early in infancy is a risk factor for an inaccurate diagnosis, post-operative enterocolitis, and a protracted post-operative recovery. The present study was primarily designed to evaluate the feasibility and efficacy of home rectal irrigation in the neonatal period and early in infancy, followed by a delayed and planned SSPT in a prospective cohort with HSCR. METHODS: Between January 2014 and December 2016, a total of 147 neonates diagnosed with HSCR were enrolled in the study. Six patients were excluded as a result of ganglion cells found in second rectal biopsies after the neonatal period. One hundred twenty-two patients successfully underwent 2-4 months of home rectal irrigation during the neonatal period, followed by a SSPT procedure after the neonatal period (group A, n = 122). Nineteen patients were not candidates for home rectal irrigation, and thus, colostomies were performed during the neonatal period followed by multi-stage procedures after the neonatal period (group B, n = 19). One hundred twenty-two healthy children, age- and gender-matched to group A were enrolled as the healthy control group for assessment of nutrition status (group C, n = 122). The birth weight, gender ratio, aganglionic segment, age, and Hirschsprung-associated enterocolitis (HAEC) score at the time of HSCR diagnosis were measured to evaluate the feasibility of home rectal irrigation in neonates and early in infancy. The nutritional indices, including weight, body length, serum albumin, serum prealbumin, serum retinol-binding protein, and incidence of HAEC after 2-4 successful home rectal irrigation, were used to assess the efficacy of home rectal irrigation. Anastomotic strictures or leakage, perianal excoriation, frequency of defecation, and morbidity of post-operative HAEC were recorded to evaluate the beneficial effects to pull through (PT), which were facilitated by home rectal irrigation. RESULTS: Higher HAEC scores and older age at the time of diagnosis of HSCR were associated with group B, compared to group A (4.34 ± 1.25 vs. 11.0 ± 2.56 [t = 18.20, p < 0.05] and 2.8 ± 1.46 days vs. 12.1 ± 5.3 days [t = 16.10, p < 0.05], respectively). The ratio of rectosigmoid HSCR to non-rectosigmoid HSCR was higher in group A than group B (104/18 vs. 4/15 [χ2 = 34.29, p < 0.05]). There were no differences in birth weight, weight at the time of diagnosis of HSCR, and gender ratio between groups A and B. There were no differences in birth weight, birth length, post-home rectal irrigation age, post-home rectal irrigation weight, post-home rectal irrigation length, and post-home rectal irrigation serum albumin between groups A and C (3.47 ± 0.42 kg vs. 3.48 ± 0.40 kg [t = 0.10, p > 0.05], 50.02 ± 0.49 cm vs. 50.05 ± 0.46 cm [t = 0.61, p > 0.05], 98.59 ± 13.34 days vs. 97.83 ± 13.58 days [t = 0.44, p > 0.05], 6.77 ± 0.66 kg vs. 6.97 ± 0.87 kg [t = 1.95, p > 0.05], 61.55 ± 2.14 cm vs. 61.70 ± 2.07 cm [t = 0.59, p > 0.05], and 41.78 ± 2.42 g/L vs. 41.85 ± 2.37 g/L [t = 0.22, p > 0.05], respectively). The rate of HAEC in the period of home rectal irrigation in group A was low; however, the post-home rectal irrigation serum prealbumin level and retinol-binding protein were significantly lower in group A than group C (0.15 ± 0.04 g/L vs. 0.17 ± 0.05 g/L [t = 3.50, p < 0.05] and 22.51 ± 7.53 g/L vs. 30.57 ± 9.26 g/L [t = 7.46, p < 0.05], respectively). There were no anastomotic strictures or leakage after definitive PT performed in group A. The frequency of defecation ranged from 2-6 times per day, 10 patients had perianal excoriation 3 months after PT, and 11 patients had post-operative HAEC during 6 months of follow-up after PT. CONCLUSION: Home rectal irrigation in neonates and early in infancy, followed by a delayed and planned SSPT is feasible and effective in patients with HSCR, and could be beneficial to definitive PT. However, for patients with an extended aganglionic segment, older age, or high HAEC score at the time of diagnosis of HSCR, rectal irrigation maybe not suitable. TRIAL REGISTRATION: This was a prospective comparative study designed to evaluate the effects of home rectal irrigation for facilitating and enhancing recovery after PT, and was registered at Clinical Trials.gov as NCT02776176.

Proteomics approach to identify serum biomarkers associated with the progression of diabetes in Korean patients with abdominal obesity.

Type 2 diabetes is a metabolic disease with a group of metabolic derangements and inflammatory reactants in the serum. Despite the substantial public health implications, markers of diabetes progression with abdominal obesity are still needed to facilitate early detection and treatment. In this study, we performed a proteomic approach to identify differential target proteins underlying diabetes progression in patients with abdominal obesity. Proteomic differences were investigated in the serum of controls and patients with prediabetes or diabetes with or without abdominal obesity by 2-DE combined with MALDI-TOF-MS. Proteomics data were validated by western blot analyses and major protein-protein interactions were assessed using a network analysis with String database. Among 245 matched protein spots, 36 exhibited marked differences in normal patients with abdominal obesity, prediabetes, and diabetes compared to levels in normal patients without abdominal obesity. Seven (Alpha-1-antichymotrypsin, Alpha-1-antitrypsin, Apolipoprotein A-I, haptoglobin, retinol-binding protein 4, transthyretin, and zinc-alpha2-glycoprotein) of these spots exhibited significant differences between normal and prediabetes/diabetes patients. After a network analysis, functional annotation using Gene Ontology indicated that most of the identified proteins were involved in lipid transport, lipid localization, and the regulation of serum lipoprotein particle levels. Our results indicated that variation in the levels of these identified protein biomarkers has been reported in normal, prediabetes and diabetic Assessment of the levels of these biomarkers may contribute to the development of biomarkers for not only early diagnosis but also in prognosis of diabetes mellitus type 2.

Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients.

BACKGROUND: Chronic pancreatitis (CP) patients frequently experience malabsorption and maldigestion, leading to micronutrient and macronutrient deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol consumption, may impact nutrition status. METHODS: We compared micronutrient antioxidant, bone metabolism, serum protein, and inflammatory marker levels in 301 CP patients and 266 controls with no known pancreatic disease. We analyzed serum prealbumin and retinol binding protein; vitamins A, D, E, and B12; osteocalcin; tumor necrosis factor-α; and C-reactive protein (CRP). We also evaluated biomarkers among subsets of patients, examining factors including time since diagnosis, body mass index, alcohol as primary etiology, diabetes mellitus, vitamin supplementation, and pancreatic enzyme replacement. RESULTS: After correcting for multiple comparisons, CP patients had significantly lower levels than controls of the following: vitamin A (40.9 vs 45.4 µg/dL) and vitamin E (α-tocopherol [8.7 vs 10.3 mg/L] and γ-tocopherol [1.8 vs 2.2 mg/L]), as well as osteocalcin (7.9 vs 10 ng/mL) and serum prealbumin (23 vs 27 mg/dL). Both patients and controls who took vitamin supplements had higher serum levels of vitamins than those not taking supplements. Compared with controls, in controlled analyses, CP patients had significantly lower levels of vitamins A, D, and E (both α-tocopherol and γ-tocopherol). CP patients also had significantly lower levels of osteocalcin, serum prealbumin, and retinol binding protein, and higher CRP. CONCLUSIONS: CP patients demonstrated lower levels of selected nutrition and bone metabolism biomarkers than controls. Diabetes and alcohol did not impact biomarkers. Vitamin supplements and pancreatic enzyme replacement therapy improved nutrition biomarkers in CP patients.

Computed tomography-quantified body composition predicts short-term outcomes after gastrectomy in gastric cancer.

Background: Malnutrition is a common and critical problem that influences outcome in cancer patients. Body composition reflects a patient's metabolic profile and physiologic reserves, which might be the true determinant of prognosis. In the present study, which aimed to identify valuable new prognostic indicators, we investigated the association between computed tomography-quantified body composition and short-term outcomes after gastrectomy for gastric cancer. Methods: Skeletal muscle index, mean muscle attenuation, and ratio of visceral-to-subcutaneous adipose tissue area (vsr) were calculated from preoperative computed tomography images. Low skeletal muscle index, low mean muscle attenuation, and high vsr were respectively termed "sarcopenia," "myosteatosis," and "visceral obesity." The association of body composition with postoperative complications and serum markers of nutrition and inflammation after radical gastrectomy were analyzed. Results: The overall complication rate was significantly higher in the sarcopenia (62.5% vs. 27.3%, p = 0.001) and myosteatosis groups (38.2% vs. 4%, p = 0.002). Patients with visceral obesity had a higher incidence of inflammatory complications (20.3% vs. 6.5%, p = 0.01). Multivariate logistic regression analysis demonstrated that sarcopenia (p = 0.013), myosteatosis (p = 0.017), and low serum retinol-binding protein (p = 0.019) were independent risk factors for overall complications. Compared with control subjects, patients with sarcopenia had lower postoperative levels of serum retinol-binding protein (p = 0.007), and patients with visceral obesity had higher levels of C-reactive protein (p = 0.026). Conclusions: Sarcopenia, myosteatosis, and visceral obesity were significantly associated with increased rates of postoperative complications and affected the postoperative nutrition and inflammation status of patients with gastric cancer.

Subclinical inflammation affects iron and vitamin A but not zinc status assessment in Senegalese children and Cambodian children and women.

OBJECTIVE: To assess the impact of the acute-phase response (APR) during inflammation on Fe, Zn and vitamin A biomarkers to allow accurate evaluation of micronutrient status in populations. DESIGN: Ferritin (FER), soluble transferrin receptor (TfR), retinol-binding protein (RBP), Zn, α1-acid glycoprotein and C-reactive protein concentrations were measured. Correction factors (CF) for each biomarker were calculated as the ratio for groups at different stages of inflammation v. the reference group without inflammation.Setting/SubjectsSenegalese (n 594) and Cambodian schoolchildren (n 2471); Cambodian women of reproductive age (n 2117). RESULTS: TfR was higher during the incubation phase (CF=1·17) and lower during early and late convalescence (CF=0·87 and 0·78). FER was higher during all phases (CF=0·83, 0·48 and 0·65, respectively). RBP was higher during incubation (CF=0·88) and lower during early convalescence (CF=1·21). No effect of inflammation on Zn status was found. CONCLUSIONS: Inflammation led to overestimation of Fe status and underestimation of vitamin A status. The response of the biomarker for vitamin A status to inflammation depended on the vitamin A status of the populations. Surprisingly, the assessment of Zn status was hardly affected by inflammation. Different phases of the APR had opposite effects on the assessment of Fe status using TfR. More research is needed to define the correct methods to adjust for inflammation in nutritional studies.

Adjusting retinol-binding protein concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its interpretation is challenging in settings where inflammation is common because RBP concentrations decrease during the acute-phase response.Objectives: We aimed to assess the relation between RBP concentrations and inflammation and malaria in preschool children (PSC) (age range: 6-59 mo) and women of reproductive age (WRA) (age range: 15-49 y) and to investigate adjustment algorithms to account for these effects.Design: Cross-sectional data from 8 surveys for PSC (n = 8803) and 4 surveys for WRA (n = 4191) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to adjust RBP concentrations in PSC in inflammation and malaria settings as follows: 1) the exclusion of subjects with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of a regression correction approach. The impact of adjustment on the estimated prevalence of VAD (defined as <0.7 µmol/L) was examined in PSC.Results: The relation between estimated VAD and CRP and AGP deciles followed a linear pattern in PSC. In women, the correlations between RBP and CRP and AGP were too weak to justify adjustments for inflammation. Depending on the approach used to adjust for inflammation (CRP+AGP), the estimated prevalence of VAD decreased by a median of 11-18 percentage points in PSC compared with unadjusted values. There was no added effect of adjusting for malaria on the estimated VAD after adjusting for CRP and AGP.Conclusions: The use of regression correction (derived from internal data), which accounts for the severity of inflammation, to estimate the prevalence of VAD in PSC in regions with inflammation and malaria is supported by the analysis of the BRINDA data. These findings contribute to the evidence on adjusting for inflammation when estimating VAD with the use of RBP.

Research, policy, and programmatic considerations from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project sought to inform the interpretation of iron and vitamin A biomarkers (ferritin, serum transferrin receptor, and retinol binding protein) in settings of prevalent inflammation as well as the prevention of and control strategies to address anemia. Our purpose is to comment on the contributions of the BRINDA to advance global knowledge with regard to iron and vitamin A status assessment in women and preschool children and to analyze the findings in terms of their rigor and usefulness for global nutrition research and programs. BRINDA investigators found that the acute-phase response is so prevalent that it must be assessed in surveys of iron and vitamin A status for valid interpretation of micronutrient biomarkers. Furthermore, they found that C-reactive protein and α-1-acid glycoprotein provide important and different information about these responses and that common survey variables cannot replace the information they provide. Developing a method for adjusting micronutrient biomarkers for the independent influence of inflammation is challenging and complex, and BRINDA has brought greater clarity to this challenge through the use of large and diverse data sets. When comparing approaches, the regression methods appear to perform best when sample sizes are sufficient and adequate statistical capacity is available. Further correction for malaria does not appear to materially alter regression-adjusted prevalence estimates. We suggest that researchers present both adjusted and unadjusted values for the micronutrient biomarkers. BRINDA findings confirm that iron deficiency is a common and consistent risk factor for anemia globally and that anemia control must combine iron interventions with control of infection and inflammation. Anemia control strategies must be informed by local data. By applying the knowledge in these studies, researchers, program planners, and evaluators working in populations with prevalent inflammation can use and interpret biomarkers with more confidence, tempered with necessary caution.

Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia.Objectives: The aims of the project were to 1) identify factors associated with inflammation, 2) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA).Design: The BRINDA database inclusion criteria included surveys that 1) were conducted after 2004, 2) had target groups of PSC, WRA, or both, and 3) used a similar laboratory methodology for the measurement of ≥1 biomarker of iron [ferritin or soluble transferrin receptor or vitamin A status (retinol-binding protein or retinol)] and ≥1 biomarker of inflammation (α-1-acid glycoprotein or C-reactive protein). Individual data sets were standardized and merged into a BRINDA database comprising 16 nationally and regionally representative surveys from 14 countries. Collectively, the database covered all 6 WHO geographic regions and contained ∼30,000 PSC and 27,000 WRA. Data were analyzed individually and combined with the use of a meta-analysis.Results: The methods that were used to standardize the BRINDA database and the analytic approaches used to address the project's research questions are presented in this article. Three approaches to adjust micronutrient biomarker concentrations in the presence of inflammation and malaria infection are presented, along with an anemia conceptual framework that guided the BRINDA project's anemia analyses.Conclusions: The BRINDA project refines approaches to interpret iron and vitamin A biomarker values in settings of inflammation and malaria infection and suggests the use of a new regression approach as well as proposes an anemia framework to which real-world data can be applied. Findings can inform guidelines and strategies to prevent and control micronutrient deficiencies and anemia globally.