Anemia: Evaluation of Suspected Anemia.

Anemia is a common condition encountered in inpatient and outpatient primary care settings. When anemia is detected, it is essential to investigate the cause to provide appropriate treatment. Patients may present with symptomatic anemia (eg, fatigue, weakness, shortness of breath), or anemia may be an incidental finding on laboratory evaluation. Initial evaluation consists of a thorough history and physical examination and a complete blood cell count (CBC). Careful examination of the CBC and the mean corpuscular volume provides important clues to the classification and cause of anemia. Supplemental tests may include a peripheral blood smear; reticulocyte count; iron panel (ie, ferritin and iron levels, total iron-binding capacity, transferrin saturation); and levels of vitamin B12, folate, lactate dehydrogenase, haptoglobin, and bilirubin.

Prevalence and aetiologies of anaemia among first trimester pregnant women in Sri Lanka; the need for revisiting the current control strategies.

BACKGROUND: The Sustainable development goals, which focus strongly on equity, aim to end all forms of malnutrition by 2030. However, a significant cause of intergenerational transfer of malnutrition, anaemia in pregnancy, is still a challenge. It is especially so in the low- and middle-income settings where possible context-specific aetiologies leading to anaemia have been poorly explored. This study explores the prevalence of etiological factors significantly contributing to anaemia in pregnancy in Sri Lanka, a lower-middle-income country with a high prevalence of malnutrition albeit robust public health infrastructure. METHODS: All first-trimester pregnant women registered in the public maternal care programme in the Anuradhapura district from July to September 2019 were invited to participate in Rajarata Pregnancy Cohort (RaPCo). After a full blood count analysis, high-performance liquid chromatography, peripheral blood film examination, serum B12 and folate levels were performed in anaemic participants, guided by an algorithm based on the red cell indices in the full blood count. In addition, serum ferritin was tested in a random subsample of 213 participants. Anaemic women in this subsample underwent B12 and folate testing. RESULTS: Among 3127 participants, 14.4% (95%CI 13.2-15.7, n = 451) were anaemic. Haemoglobin ranged between 7.4 to 19.6 g/dl. 331(10.6%) had mild anaemia. Haemoglobin ≥13 g/dl was observed in 39(12.7%). Microcytic, normochromic-normocytic, hypochromic-normocytic and macrocytic anaemia was observed in 243(54%), 114(25.3%), 80(17.8%) and two (0.4%) of full blood counts in anaemic women, respectively. Microcytic anaemia with a red cell count ≥5 * 106 /µl demonstrated a 100% positive predictive value for minor haemoglobinopathies. Minor hemoglobinopathies were present in at least 23.3%(n = 105) of anaemic pregnant women. Prevalence of iron deficiency, B12 deficiency and Southeast Asian ovalocytosis among the anaemic was 41.9% (95%CI 26.4-59.2), 23.8% (95%CI 10.6-45.1) and 0.9% (95%CI 0.3-2.3%), respectively. Folate deficiency was not observed. CONCLUSION: Even though iron deficiency remains the primary cause, minor hemoglobinopathies, B 12 deficiency and other aetiologies substantially contribute to anaemia in pregnancy in this study population. Public health interventions, including screening for minor hemoglobinopathies and multiple micronutrient supplementation in pregnancy, should be considered in the national programme for areas where these problems have been identified.

Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study.

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10-11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

Bloodless Management of the Anemic Patient in the Emergency Department.

Anemia is a commonly encountered condition in emergency medicine; transfusion of packed red blood cells is commonly performed for anemic patients in the emergency department (ED), but some patients are unable to accept transfusion of blood products due to medical or religious concerns. The unique, acute, and time-sensitive nature of emergency medicine practice requires that physicians maintain an enhanced awareness of bloodless medicine treatment modalities. Identification of bloodless medicine patient preferences in the ED can help guide physicians in the recommendation of acceptable methods of treating anemia in this patient population. A focus on early hemostasis and resuscitation, instead of attempts to convince the patient to accept blood transfusion, can be lifesaving in patients with acute bleeding. Treatment strategies including the use of methods to reduce unnecessary blood loss, enhance red blood cell production, and increase the oxygen-carrying capacity of blood should also be considered early in patient presentation. Timely involvement of the Hospital Liaison Committee can help facilitate successful interpersonal communication and shared decisionmaking between emergency physicians and bloodless medicine patients. By embracing an understanding of bloodless medicine patient needs as well as available treatment strategies, ED physicians can contribute to optimal overall outcomes for anemic bloodless medicine patients.

Evaluation of recombinant human erythropoietin responsiveness by measuring erythrocyte creatine content in haemodialysis patients.

BACKGROUND: One of the main causes of anaemia in patients with end-stage renal disease is relative deficiency in erythropoietin production. Eythropoiesis stimulating agent (ESA), a potent haematopoietic growth factor, is used to treat anaemia in haemodialysis patients. The effect of ESA is usually assessed by haematological indices such as red blood cell count, haemoglobin concentration and haematocrit, but erythrocyte indices do not provide information of the rapid change in erythropoietic activity. As erythrocyte creatine directly assess erythropoiesis, the aim of this study was to evaluate the effect of ESA in haemodialysis patients by measuring the erythrocyte creatine content. METHODS: ESA dose was fixed 3 months prior to the enrollment and was maintained throughout the entire study period. Erythrocyte creatine was measured with haematologic indices in 83 haemodialysis patients. Haemoglobin was also measured 3 months after. RESULTS: ESA dose (152.4 ± 62.9 vs. 82.2 ± 45.5 units/kg/week, P = 0.0001) and erythrocyte creatine (2.07 ± 0.73 vs. 1.60 ± 0.41 µmol/gHb, p = 0.0003) were significantly higher in 27 patients with haemoglobin <10 g/dL compared to 56 patients with haemoglobin ≥10 g/dL. There was a fair correlation between ESA dose and the concentration of creatine in the erythrocytes (r = 0.55, P < 0.0001). Increase in haemoglobin (>0.1 g/dL) was observed in 37 patients, whereas haemoglobin did not increase in 46 patients. Erythrocyte creatine levels were significantly higher in those patients with an increase in haemoglobin compared to those without (2.04 ± 0.64 vs. 1.52 ± 0.39 µmol/gHb, p < 0.0001). When 8 variables (ESA dose, erythropoietin resistance index, C-reactive protein, intact parathyroid hormone, iron supplementation, presence of anaemia, erythrocyte creatine and reticulocyte) were used in the multivariate logistic analysis, erythrocyte creatine levels emerged as the most important variable associated with increase in haemoglobin (Chi-square = 6.19, P = 0.01). CONCLUSION: Erythrocyte creatine, a useful marker of erythropoietic capacity, is a reliable marker to estimate ameliorative effectiveness of ESA in haemodialysis patients.

U-Shaped Association between Maternal Hemoglobin and Low Birth Weight in Rural Bangladesh.

Low birth weight (LBW) is associated with a higher risk of neonatal mortality and the development of adult-onset chronic disease. Understanding the ongoing contribution of maternal hemoglobin (Hgb) levels to the incidence of LBW in South Asia is crucial to achieve the World Health Assembly global nutrition target of a 30% reduction in LBW by 2025. We enrolled pregnant women from the rural Tangail District of Bangladesh in a Maternal Newborn Health Registry established under The Global Network for Women's and Children's Health Research. We measured the Hgb of pregnant women at enrollment and birth weights of all infants born after 20 weeks gestation. Using logistic regression to adjust for multiple potential confounders, we estimated the association between maternal Hgb and the risk of LBW. We obtained Hgb measurements and birth weights from 1,665 mother-child dyads between July 2019 and April 2020. Using trimester-specific cutoffs for anemia, 48.3% of the women were anemic and the mean (±SD) Hgb level was 10.6 (±1.24) g/dL. We identified a U-shaped relationship where the highest risk of LBW was seen at very low (< 7.0 g/dL, OR = 2.00, 95% CI = 0.43-7.01, P = 0.31) and high (> 13.0 g/dL, OR = 2.17, 95% CI = 1.01-4.38, P = 0.036) Hgb levels. The mechanisms underlying this U-shaped association may include decreased plasma expansion during pregnancy and/or iron dysregulation resulting in placental disease. Further research is needed to explain the observed U-shaped relationship, to guide iron supplementation in pregnancy and to minimize the risk of LBW outcomes.

Dietary Determinants of Anemia in Children Aged 6-36 Months: A Cross-Sectional Study in Indonesia.

Anemia has been acknowledged as worldwide problem, including in Indonesia. This cross-sectional study aims to explore dietary determinants as risk factors for anemia in children aged 6-36 months living in a poor urban area of Jakarta. The study was done in Kampung Melayu sub-district in Jakarta, Indonesia. Data was collected within two weeks in September-October 2020. A structured questionnaire for a 24-h recall and a semi-quantitative Food Frequency Questionnaire (FFQ) were used to collect the dietary intake data, and venous blood was withdrawn to determine the hemoglobin levels. Bivariate chi-square and multiple logistic regression tests were executed to explore the dietary determinant factors for anemia. We recruited 180 subjects. The average hemoglobin concentration was 11.4 ± 1.7 mg/dL; the anemia prevalence was 29.4%. The following variables were significantly associated with higher risk of anemia: no cow's milk formula consumption, inadequate intake of fats, protein, calcium, vitamin D, iron, zinc, vitamin A, vitamin C, vitamin B6, and vitamin B12. Only cow's milk formula consumption and zinc intake were revealed as the determinant factors of anemia. In conclusion, the prevalence of anemia was 29.4% among children aged 6-36 months old. Anemia was significantly associated with two dietary determinants as risk factors that are cow's milk formula consumption and zinc intake.

Pharmacological and clinical evaluation of deferasirox formulations for treatment tailoring.

Deferasirox (DFX) is the newest among three different chelators available to treat iron overload in iron-loading anaemias, firstly released as Dispersible Tablets (DT) and more recently replaced by Film-Coated Tablets (FCT). In this retrospective observational study, pharmacokinetics, pharmacodynamics, and safety features of DFX treatment were analyzed in 74 patients that took both formulations subsequently under clinical practice conditions. Bioavailability of DFX FCT compared to DT resulted higher than expected [Cmax: 99.5 (FCT) and 69.7 (DT) µMol/L; AUC: 1278 (FCT) and 846 (DT), P < 0.0001]. DFX FCT was also superior in scalability among doses. After one year of treatment for each formulation, no differences were observed between the treatments in the overall iron overload levels; however, DFX FCT but not DT showed a significant dose-response correlation [Spearman r (dose-serum ferritin variation): - 0.54, P < 0.0001]. Despite being administered at different dosages, the long-term safety profile was not different between formulations: a significant increase in renal impairment risk was observed for both treatments and it was reversible under strict monitoring (P < 0.002). Altogether, these data constitute a comprehensive comparison of DFX formulations in thalassaemia and other iron-loading anaemias, confirming the effectiveness and safety characteristics of DFX and its applicability for treatment tailoring.

Therapeutic effects of Sheng Xue Fang in a cyclophosphamide-induced anaemia mouse model.

CONTEXT: Sheng Xue Fang (SXF) has been used to treat anaemia for decades with good efficacy. OBJECTIVE: To study the effect and possible mechanism of SXF to restore haematopoietic function. MATERIALS AND METHODS: Balb/c mice (10 per/group, half male, half female) were treated with SXF (three dose groups, 8.5, 17, and 22.1 g/kg) by gavage for 14 days, and cyclophosphamide (80 mg/kg) was injected on days 10-12. Only injection of cyclophosphamide (negative control) or physiological saline (blank control) were included as controls. The spleen and femur were processed for histopathology. Active components and the target of SXF were screened. The target was used for gene enrichment and protein-protein interaction (PPI) analysis. RESULTS: Red blood cell relative changes in the SXF group (low: -5.50 ± 1.58%; medium: -11.11 ± 4.15%; high: -8.81 ± 2.67%) and relative negative control (26.21 ± 2.51%) significantly increased (all p < 0.01) in female mice. Haemoglobin and red blood cell-specific volume showed the same trend. However, SXF did not have significant effects on male mice. Splenic index in the medium group (4.44 ± 0.46%) relative negative control (3.38 ± 0.10%) significantly improved (p < 0.01) in female mice. Using network pharmacology, 77 active components and 337 targets were screened from SXF. These targets are closely related to the mitogen-activated protein kinase pathway. CONCLUSIONS: SXF has good clinical application potential. However, the mechanism requires in-depth research. Our findings are of great significance in anaemia treatment and provide a new perspective for Chinese medicine research.

Haemoglobin thresholds to define anaemia in a national sample of healthy children and adolescents aged 1-19 years in India: a population-based study.

BACKGROUND: WHO's haemoglobin cutoffs to define anemia were based on five studies of predominantly White adult populations, done over 50 years ago. Therefore, a general re-examination of the existing haemoglobin cutoffs is warranted for global application, in representative healthy populations of children and adults. Such data are scarce in low-income and middle-income countries; however, a 2019, large-scale, nationally representative survey of children and adolescents aged 0-19 years in India (Comprehensive National Nutrition Survey [CNNS]) offered an opportunity for this re-examination. Using this survey, we aimed to assess the age-specific and sex-specific percentiles of haemoglobin and cutoffs to define anaemia in the CNNS population. METHODS: For this population-based study, we constructed age-specific and sex-specific haemoglobin percentiles from values reported for a defined healthy population in the CNNS, which used rigorous quality control measures during sample collection and in the laboratory analyses. To obtain a healthy population, we excluded participants with iron, folate, vitamin B12, and retinol deficiencies; inflammation; variant haemoglobins (haemoglobin A2 and haemoglobin S); and history of smoking. We considered age-specific and sex-specific 5th percentiles of haemoglobin derived for this healthy population as the study cutoff to define anaemia. We compared these with existing WHO cutoffs to assess significant differences between them at each year of age and sex for quantifying the prevalence of anaemia in the entire CNNS sample. FINDINGS: Between Feb 24, 2016, and Oct 26, 2018, the CNNS survey collected blood samples from 49 486 individuals. 41 210 participants had a haemoglobin value, 8087 of whom were included in our study and comprised the primary analytical sample. Compared with existing WHO cutoffs, the study cutoffs for haemoglobin were lower at all ages, usually by 1-2 g/dL, but more so in children of both sexes aged 1-2 years and in girls aged 10 years or older. Aanemia prevalence with the study cutoffs was 19·2 percentage points lower than with WHO cutoffs in the entire CNNS sample with valid haemoglobin values across all ages and sexes (10·8% with study cutoffs vs 30·0% with WHO cutoffs). INTERPRETATION: These findings support the re-examination of WHO haemoglobin cutoffs to define anaemia. Our haemoglobin reference percentiles, derived from healthy participants in a large representative Indian survey, are suitable for national use in India. Substantial variations in the 5th percentile of haemoglobin values across the 1-19 years age range and between sexes argue against constructing common cutoffs in stratified age groups for convenience. FUNDING: None. TRANSLATIONS: For the Hindi, Punjabi, Tamil and Kannada translations of the abstract see Supplementary Materials section.

Multiple Micronutrients, Including Zinc, Selenium and Iron, Are Positively Associated with Anemia in New Zealand Aged Care Residents.

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.

Ferric carboxymaltose vs. ferrous sulfate for the treatment of anemia in advanced chronic kidney disease: an observational retrospective study and cost analysis.

In non-dialysis-dependent chronic kidney disease (NDD-CKD), erythropoiesis-stimulating agents (ESAs) and iron supplementation are essential for anemia management. Ferric carboxymaltose (FCM) is a relatively novel intravenous iron formulation used in different clinical settings, although scarce data exist in NDD-CKD patients. Primary objective of this study was to retrospectively evaluate the efficacy of FCM compared with oral ferrous sulfate for the treatment of iron-deficiency anemia in a cohort of NDD-CKD patients, considering also the treatment costs. This was a monocentric, retrospective observational study reviewing 349 NDD-CKD patients attending an outpatient clinic between June 2013 and December 2016. Patients were treated by either FCM intravenous infusion or oral ferrous sulfate. We collected serum values of hemoglobin, ferritin and transferrin saturation (TSAT) and ESAs doses at 12 and 18 months. The costs related to both treatments were also analysed. 239 patients were treated with FCM intravenous infusion and 110 patients with oral ferrous sulfate. The two groups were not statistically different for age, BMI and eGFR values. At 18 months, hemoglobin, serum ferritin and TSAT values increased significantly from baseline in the FCM group, compared with the ferrous sulfate group. ESAs dose and rate of infusion decreased only in the FCM group. At 18 months, the treatment costs, analysed per week, was higher in the ferrous sulfate group, compared with the FCM group, and this was mostly due to a reduction in ESAs prescription in the FCM group. Routine intravenous FCM treatment in an outpatient clinic of NDD-CKD patients results in better correction of iron-deficiency anemia when compared to ferrous sulfate. In addition to this, treating NDD-CKD patients with FCM leads to a significant reduction of the treatment costs by reducing ESAs use.

SEOM clinical guidelines for anaemia treatment in cancer patients (2020).

Anaemia is defined by the presence of haemoglobin (Hb) levels < 13 g/dL in men and 12 g/dL in women. Up to 39% of cancer patients present it at the time of diagnosis and up to 40% have iron deficiency. Anaemia causes fatigue, functional deterioration and a reduction in the quality of life; it has also been associated with a poorer response to anti-tumour treatment and lower survival. Basic diagnostic tests for anaemia are simple and should be a routine part of clinical practice. These guidelines review the available evidence on the use of different therapies for treating anaemia: erythropoiesis-stimulating agents, iron supplements, and transfusion of blood products.

Prediction of anemia at delivery.

We aimed to assess risk factors for anemia at delivery by conducting a secondary analysis of a prospective cohort study database including 1527 women who delivered vaginally ≥ 36 gestational weeks. Anemia (Hemoglobin (Hb) < 10.5 g/dL) was assessed at delivery. A complete blood count results during pregnancy as well as maternal and obstetrical characteristics were collected. The primary endpoint was to determine the Hb cutoff between 24 and 30 gestational weeks that is predictive of anemia at delivery by using the area under the curve (AUC) of the receiver operating characteristic curve. Independent risk factors for anemia at delivery were assessed using stepwise multivariable logistic regression. Hb and infrequent iron supplement treatment were independent risk factors for anemia at delivery (OR 0.3 95%CI [0.2-0.4] and OR 2.4 95%CI [1.2-4.8], respectively; C statistics 83%). Hb 10.6 g/dL was an accurate cutoff to predict anemia at delivery (AUC 80% 95%CI 75-84%; sensitivity 75% and specificity 74%). Iron supplement was beneficial to prevent anemia regardless of Hb value. Altogether, Hb should be routinely tested between 24 and 30 gestational weeks to screen for anemia. A flow chart for anemia screening and treatment during pregnancy is proposed in the manuscript.Trial registration: ClinicalTrials.gov Identifier: NCT02434653.

Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions.

Cancer is often accompanied by worsening of the patient's iron profile, and the resulting anemia could be a factor that negatively impacts antineoplastic treatment efficacy and patient survival. The first line of therapy is usually based on oral or intravenous iron supplementation; however, many patients remain anemic and do not respond. The key might lie in the pathogenesis of the anemia itself. Cancer-related anemia (CRA) is characterized by a decreased circulating serum iron concentration and transferrin saturation despite ample iron stores, pointing to a more complex problem related to iron homeostatic regulation and additional factors such as chronic inflammatory status. This review explores our current understanding of iron homeostasis in cancer, shedding light on the modulatory role of hepcidin in intestinal iron absorption, iron recycling, mobilization from liver deposits, and inducible regulators by infections and inflammation. The underlying relationship between CRA and systemic low-grade inflammation will be discussed, and an integrated multitarget approach based on nutrition and exercise to improve iron utilization by reducing low-grade inflammation, modulating the immune response, and supporting antioxidant mechanisms will also be proposed. Indeed, a Mediterranean-based diet, nutritional supplements and exercise are suggested as potential individualized strategies and as a complementary approach to conventional CRA therapy.

Multiple micronutrient supplementation improves micronutrient status in primary school children in Hai Phong City, Vietnam: a randomised controlled trial.

We aimed to determine the efficacy of multiple micronutrient supplementation on the biomarkers of iron, zinc, and vitamin A status across anthropometric status categories in Vietnamese school children. In this 22-week randomised controlled trial, 347 undernourished, normal weight, or overweight/obese children aged 6-9 years were allocated to receive every school day a multiple micronutrient supplement (10 mg iron, 10 mg zinc, 400 µg vitamin A) or a placebo. Haematological indices; circulating ferritin, zinc, and retinol (corrected for inflammation); and C-reactive protein were measured at baseline and 22 weeks. At week 22, linear mixed models showed that mean corpuscular volume increased by 0.3 fL, serum ferritin by 9.1 µg/L, plasma zinc by 0.9 µmol/L, and plasma retinol by 15%, and the prevalence of zinc deficiency decreased by 17.3% points in the intervention group compared to placebo. No intervention effects were found for other haematological indices, or the prevalence of anaemia. Multiple micronutrient supplementation for 22 weeks improved the biomarkers of zinc and vitamin A status and some biomarkers of iron status, and reduced the prevalence of zinc deficiency in Vietnamese school children.Trial registration: This trial was registered on 06/09/2016 at www.anzctr.org.au as ACTRN12616001245482.

Enteral Vitamin B12 Supplementation Is Effective for Improving Anemia in Patients Who Underwent Total Gastrectomy.

BACKGROUND: This study aimed to investigate the efficacy of enteral supplementation of vitamin B12 for vitamin B12 deficiency in patients who underwent total gastrectomy for gastric cancer. METHODS: The study enrolled 133 patients who underwent total gastrectomy for gastric cancer at Kochi Medical School. Clinical data were obtained to investigate associations between vitamin B12 supplementation and vitamin B12 levels. Vitamin B12 deficiency was defined as serum vitamin B12 less than 200 pg/mL. Baseline characteristics and changes in hematological variables, including vitamin B12 levels, were examined. RESULTS: Vitamin B12 deficiency was present in 71.4% of the 133 patients. Vitamin B12 levels at 3, 6, and 12 months after enteral supplementation were 306 pg/mL, 294 pg/mL, and 367 pg/mL, respectively, which were all significantly higher than those before supplementation (p < 0.001 for all comparisons). The median red blood cell count at 3, 6, and 12 months after enteral supplementation were 380 × 104/mm3, 394 × 104/mm3, and 395 × 104/mm3, respectively, which were all significantly higher than those before supplementation (p = 0.020, p = 0.001, and p = 0.003, respectively). Vitamin B12 levels at 3, 6, and 12 months after supplementation were significantly higher in patients supplemented enterally than those supplemented parenterally (p < 0.001 for all comparisons). CONCLUSIONS: Vitamin B12 deficiency was found in 71.4% of postoperative patients who underwent total gastrectomy for gastric cancer, and enteral vitamin B12 supplements might be effective to improve anemia in these patients.

Di(2-ethylhexyl) adipate plasticizer triggers hepatic, brain, and cardiac injury in rats: Mitigating effect of Peganum harmala oil.

Di(2-ethylhexyl) adipate (DEHA) is a widely used plasticizer and prevalent environmental contaminant. In this study, DEHA concentrations in the milk, cheese, and butter samples wrapped with food-grade commercial polyethylene films and stored at 4 °C for 30 days were detected using gas chromatographic analysis. Also, the effects of exposure to a high dose of DEHA for a long duration on the liver, brain, and heart of Wistar rats were assessed. Besides, the possible beneficial effect of Peganum harmala oil (PGO), in relieving DEHA induced adverse effects was explored. For this purpose, four groups (8 rats/group) were orally given physiological saline, PGO (320 mg/kg bwt), DEHA (2000 mg/kg bwt), or PGO + DEHA for 60 days. The results revealed that the DEHA concentrations in the tested dairy products were ordered as follows: (butter > cheese > milk). Notably, the detected levels in butter were higher than the specific migration limit in foods. DEHA induced a significant increase in the serum levels of glucose, alanine transaminase, aspartate transaminase, acetylcholine esterase, creatine kinase-myocardium bound, malondialdehyde, tumor necrosis factor-α, and interleukin-1ß. But, significant hypoproteinemia, hypoalbuminemia, hypoglobulinemia, and hypocholesterolemia were evident following DEHA exposure. A significant reduction in the serum level of superoxide dismutase, reduced glutathione, and brain-derived neurotrophic factor was recorded. Besides, a significant downregulation in hepatic CYP2E1, brain glial fibrillary acidic protein, and cardiac troponin I gene expression was noticed. Moreover, DEHA exposure induced a significant decrease in Bcl-2 immunolabeling, but Caspase-3 immunoexpression was increased. On the contrary, PGO significantly recused DEHA injurious impacts. Therefore, PGO could represent a promising agent for preventing DEHA-induced hepatotoxicity, neurotoxicity, and cardiotoxicity.

Wheat flour fortification with iron and other micronutrients for reducing anaemia and improving iron status in populations.

BACKGROUND: Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations. OBJECTIVES: To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, 21 other databases and two trials registers up to 21 July 2020, together with contacting key organisations to identify additional studies. SELECTION CRITERIA: We included cluster- or individually-randomised controlled trials (RCTs) carried out among the general population from any country, aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. We included trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risks of bias. We followed Cochrane methods in this review. MAIN RESULTS: Our search identified 3538 records, after removing duplicates. We included 10 trials, involving 3319 participants, carried out in Bangladesh, Brazil, India, Kuwait, Philippines, South Africa and Sri Lanka. We identified two ongoing studies and one study is awaiting classification. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias. Three trials used 41 mg to 60 mg iron/kg flour, three trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial used various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate. All included studies contributed data for the meta-analyses. Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added may reduce by 27% the risk of anaemia in populations (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.55 to 0.97; 5 studies, 2315 participants; low-certainty evidence). It is uncertain whether iron-fortified wheat flour with or without other micronutrients reduces iron deficiency (RR 0.46, 95% CI 0.20 to 1.04; 3 studies, 748 participants; very low-certainty evidence) or increases haemoglobin concentrations (in g/L) (mean difference MD 2.75, 95% CI 0.71 to 4.80; 8 studies, 2831 participants; very low-certainty evidence). No trials reported data on adverse effects in children (including constipation, nausea, vomiting, heartburn or diarrhoea), except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to the risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (mean difference (MD) 0.04, 95% CI -0.02 to 0.11; 2 studies, 558 participants; moderate-certainty evidence). Iron-fortified wheat flour with other micronutrients added versus unfortified wheat flour (nil micronutrients added) It is unclear whether wheat flour fortified with iron, in combination with other micronutrients decreases anaemia (RR 0.77, 95% CI 0.41 to 1.46; 2 studies, 317 participants; very low-certainty evidence). The intervention probably reduces the risk of iron deficiency (RR 0.73, 95% CI 0.54 to 0.99; 3 studies, 382 participants; moderate-certainty evidence) and it is unclear whether it increases average haemoglobin concentrations (MD 2.53, 95% CI -0.39 to 5.45; 4 studies, 532 participants; very low-certainty evidence). No trials reported data on adverse effects in children. Nine out of 10 trials reported sources of funding, with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials. AUTHORS' CONCLUSIONS: Fortification of wheat flour with iron (in comparison to unfortified flour, or where both groups received the same other micronutrients) may reduce anaemia in the general population above two years of age, but its effects on other outcomes are uncertain. Iron-fortified wheat flour in combination with other micronutrients, in comparison with unfortified flour, probably reduces iron deficiency, but its effects on other outcomes are uncertain. None of the included trials reported data on adverse side effects except for risk of infection or inflammation at the individual level. The effects of this intervention on other health outcomes are unclear. Future studies at low risk of bias should aim to measure all important outcomes, and to further investigate which variants of fortification, including the role of other micronutrients as well as types of iron fortification, are more effective, and for whom.

Intervention of standardized ethanol leaf extract of Annickia polycarpa, (DC.) Setten and Maas ex I.M. Turner. (Annonaceae), in Plasmodium berghei infested mice produced anti-malaria action and normalized gross hematological indices.

ETHNOPHARMACOLOGICAL RELEVANCE: Malaria is a global public health burden due to large number of annual infections and casualties caused by its hematological complications. The bark of Annickia polycarpa is an effective anti-malaria agent in African traditional medicine. However, there is no standardization parameters for A. polycarpa. The anti-malaria properties of its leaf are also not known. AIM OF THE STUDY: To standardize the ethanol leaf extract of A. polycarpa (APLE) and investigate its anti-malaria properties and the effect of its treatment on hematological indices in Plasmodium berghei infected mice in the Rane's test. MATERIALS AND METHODS: Malaria was induced by inoculating female ICR mice with 1.0 × 107P. berghei-infected RBCs in 0.2 mL (i.p.) of blood. Treatment was commenced 3 days later with APLE 50, 200, 400 mg/kg p.o., Quinine 30 mg/kg i.m. (Standard drug) or sterile water (Negative control) once daily per group for 4 successive days. Anti-malarial activity and gross malaria indices such as hyperparasitemia, mean change in body weight and mean survival time (MST) were determined for each group. Changes in white blood cells (WBCs), red blood cells (RBCs), platelets (PLT) counts, hemoglobin (HGB) concentration, hematocrit (HCT) and mean corpuscular volume (MCV) were also measured in the healthy mice before infection as baseline and on day 3 and 8 after inoculation using complete blood count. Standardization was achieved by UHPLC-MS chemical fingerprint analysis and quantitative phytochemical tests. RESULTS: APLE, standardized to its total alkaloids, phenolics and saponin contents, produced significant (P < 0.05) dose-dependent clearance of mean hyperparasitemia of 22.78 ± 0.93% with the minimum parasitemia level of 2.01 ± 0.25% achieved at 400 mg/kg p.o. on day 8. Quinine 30 mg/kg i.m. achieved a minimum parasitemia level of 6.15 ± 0.92%. Moreover, APLE (50-400 mg/kg p.o.) evoked very significant anti-malaria activity of 89.22-95.50%. Anti-malaria activity of Quinine 30 mg/kg i.m. was 86.22%. APLE also inverse dose-dependently promotes weight gain with the effect being significant (P < 0.05) at 50 mg/kg p.o. Moreover, APLE dose-dependently increased the MST of malaria infested mice with 100% survival at 400 mg/kg p.o. Quinine 30 mg/kg i.m. also produce 100% survival rate but did not promote (P > 0.05) weight gain. Hematological studies revealed the development of leukocytopenia, erythrocytosis, microcytic anemia and thrombocytopenia in the malaria infected mice which were reverted with the treatment of APLE 50-400 mg/kg p.o. or Quinine 30 mg/kg i.m. but persisted in the negative control. The UHPLC-MS fingerprint analysis of APLE led to identification of one oxoaporphine and two aporphine alkaloids (1-3). Alkaloids 1 and 3 are being reported in this plant for the first time. CONCLUSION: These results indicate that APLE possessed significant anti-malaria, immunomodulatory, erythropoietic and hematinic actions against malaria infection. APLE also has the ability to revoke deleterious physiological alteration produced by malaria and hence, promote clinical cure. These properties of APLE are due to its constituents especially, aporphine and oxoaporphine alkaloids.