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Non-celiac wheat sensitivity (WS) is considered a new clinical entity. An increasing percentage of the general population avoids gluten ingestion. However, the real existence of this condition is debated and specific markers are lacking. Our aim was thus to demonstrate the existence of WS and define its clinical, serologic, and histological markers. We reviewed the clinical charts of all subjects with an irritable bowel syndrome (IBS)-like presentation who had been diagnosed with WS using a double-blind placebo-controlled (DBPC) challenge in the years 2001-2011. One hundred celiac disease (CD) patients and fifty IBS patients served as controls. Two hundred and seventy-six patients with WS, as diagnosed by DBPC challenge, were included. Two groups showing distinct clinical characteristics were identified: WS alone (group 1) and WS associated with multiple food hypersensitivity (group 2). As a whole group, the WS patients showed a higher frequency of anemia, weight loss, self-reported wheat intolerance, coexistent atopy, and food allergy in infancy than the IBS controls. There was also a higher frequency of positive serum assays for IgG/IgA anti-gliadin and cytometric basophil activation in \"in vitro\" assay. The main histology characteristic of WS patients was eosinophil infiltration of the duodenal and colon mucosa. Patients with WS alone were characterized by clinical features very similar to those found in CD patients. Patients with multiple food sensitivity were characterized by clinical features similar to those found in allergic patients. Our data confirm the existence of non-celiac WS as a distinct clinical condition. We also suggest the existence of two distinct populations of subjects with WS: one with characteristics more similar to CD and the other with characteristics pointing to food allergy.

Cancer-related anemia is a cytokine-mediated disorder resulting from complex interactions between tumor cells and the immune system. Overexpression of certain inflammatory cytokines results in shortened survival of red blood cells, suppression of erythroid progenitor cells, impaired iron utilization, and inadequate erythropoietin production. Numerous other factors may also contribute to the development of anemia in cancer patients. The European Cancer Anaemia Survey (ECAS) has provided the most current, comprehensive, prospectively collected data on the incidence and prevalence of anemia among cancer patients, as well as important perspectives on anemia treatment and relationship of hemoglobin and performance status. ECAS enrolled over 15,000 treated and untreated patients with various malignancies from cancer centers in 24 European countries and followed them for up to 6 months. The initial analysis of the ECAS data revealed that 39% of the total cancer patient population was anemic (hemoglobin <12.0 g/dl) at enrollment, although the rate varied according to tumor type, disease status, and cancer treatment status. Of the patients who were not anemic at enrollment and started cancer treatment during the survey, those undergoing chemotherapy – either alone or in combination with radiotherapy – had the highest incidence of anemia (63 and 42%, respectively). Low hemoglobin levels correlated with poor performance status and only 40% of patients who were anemic at some time during the survey received treatment for their anemia. These findings are noteworthy, since a growing body of clinical evidence indicates that the treatment of anemia can significantly improve patients’ quality of life and may also improve the clinical outcome.

Aflatoxin B1 (AFB1) is a common toxic mycotoxin and is detectable in pregnant women. Animal studies have revealed that AFB1 caused the lysis of erythrocytes and a decrease in hemoglobin. We conducted a prospective cohort study in Guangxi, China, in order to evaluate the association between AFB1 exposure and anemia in pregnant women during the entire pregnancy. A total of 616 pregnant women from the Guangxi Zhuang Birth Cohort were included in the study. Serum AFB1-albumin (AFB1-ALB) adduct levels were measured. The effect of AFB1-ALB adducts on hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed by using multivariable linear regression. The risks of anemia from AFB1-ALB adduct exposure were assessed by multivariable logistic regression. We found that the AFB1-ALB adduct was significantly associated with a decrease in Hb (β = −4.99, 95% CI: −8.42, −1.30), MCV (β = −4.58, 95% CI: −7.23, −1.94), MCH (β = −1.86, 95% CI: −2.87, −0.85), and MCHC (β = −5.23, 95% CI: −8.28, −2.17) in the first trimester with the third tertile of AFB1-ALB adducts when compared with the first tertile. Furthermore, the third tertile of the AFB1-ALB adduct significantly increased the risk of anemia by 2.90 times than compared to the first tertile in the first trimester (OR = 3.90, 95% CI: 1.67, 9.14). A significant positive does–response relationship existed between AFB1-ALB adduct levels and anemia risk (Ptrend = 0.001). When dividing anemia types, we only found that the third tertile of AFB1-ALB adduct increased the risk of microcytic hypochromic anemia (MHA) in the first trimester (OR = 14.37, 95% CI: 3.08, 67.02) and second trimester (OR = 4.75, 95% CI: 1.96, 11.51). These findings demonstrate the correlation between maternal AFB1 exposure during early pregnancy and risk of anemia, especially MHA, and during different trimesters in Southern China. More efforts should be made to diminish AFB1 exposure for pregnant women.

A 64-year-old woman presented to the emergency department with a 3-month history of fatigue and shortness of breath, which had worsened in the past few weeks.

Background At present, the methods generally used to detect α-thalassemia mutations are confined to detecting common mutations, which may lead to misdiagnosis or missed diagnosis. The single-molecule real-time (SMRT) sequencing enables long-read single-molecule sequencing with high detection accuracy, and long-length DNA chain reads in high-fidelity read mode. This study aimed to identify novel large deletions and complex variants in the α-globin locus in Chinese population. Methods We used SMRT sequencing to detect rare and complex variants in the α-globin locus in four individuals whose hematological data indicated microcytic hypochromic anemia. However, the conventional thalassemia detection result was negative. Multiplex ligation-dependent probe amplification and droplet digital polymerase chain reaction were used to confirm SMRT sequencing results. Results Four novel large deletions were observed ranging from 23 to 81 kb in the α-globin locus. One patient also had a duplication of upstream of HBZ in the deletional region, while another, with a 27.31-kb deletion on chromosome 16 (hg 38), had abnormal hemoglobin Siriraj (Hb Siriraj). Conclusion We first identified the four novel deletions in the α-globin locus using SMRT sequencing. Considering that the conventional methods might lead to misdiagnosis or missed diagnosis, SMRT sequencing proved to be an excellent method to discover rare and complex variants in thalassemia, especially in prenatal diagnosis.

Iron status is the result of the balance between the rate of erythropoiesis and the amount of the iron stores. Direct consequence of an imbalance between the erythroid marrow iron requirements and the actual supply is a reduction of red cell hemoglobin content, which causes hypochromic mature red cells and reticulocytes. The diagnosis of iron deficiency is particularly challenging in patients with acute or chronic inflammatory conditions because most of the biochemical markers for iron metabolism (serum ferritin and transferrin ) are affected by acute phase reaction. For these reasons, interest has been generated in the use of erythrocyte and reticulocyte parameters, available on the modern hematology analyzers. Reported during blood analysis routinely performed on the instrument, these parameters can assist in early detection of clinical conditions (iron deficiency, absolute, or functional; ineffective erythropoiesis, including iron restricted or thalassemia), without additional cost. Technological progress has meant that in recent years modern analyzers report new parameters that provide further information from the traditional count. Nevertheless these new parameters are exclusive of each manufacturer, and they are patented. This is an update of these new laboratory test biomarkers of hypochromia reported by different manufactures, their meaning, and clinical utility on daily practice.

The purpose of this study is to investigate the impact of a reduction of hemoglobin (Hb) content in the erythrocytes as estimated by mean corpuscular hemoglobin concentration (MCHC) on long-term clinical outcomes in nonanemic patients with heart failure (HF). We prospectively enrolled 1,579 subjects with HF who underwent coronary angiography enrolled in the GeneBank study with 5-year follow-up of all-cause mortality. Levels of Hb and MCHC were assessed at enrollment and after 6 months of follow-up. Anemia was defined as Hb levels <13 g/dl in men and <12 g/dl in women. In our nonanemic cohort (n = 785, 49.7%), mean Hb and median MCHC were 13.8 ± 1.1 g/dl and 34.3 g/dL (interquartile range 33.6 to 35), respectively. Nonanemic patients with heart failure with lower MCHC had higher mortality risk (quartiles 1 vs 4, hazard ratio = 2.1, 95% confidence interval 1.4 to 3.3, p = 0.001). In a subset of nonanemic patients with persistent normal Hb on follow-up (n = 206), the mean time between baseline and follow-up MCHC levels was 169.3 ± 41.6 days. In comparison with patients with levels of MCHC more than the first quartile (≥33.6 g/dl) on baseline and follow-up, patients with persistently low MCHC (<33.6 g/dl) had a significantly increased mortality risk (log rank <0.001). All models remained significant even after adjusting for traditional cardiac risk factors, left ventricular ejection fraction, baseline Hb levels, and mean corpuscular volume. In conclusion, relative hypochromia is an independent predictor of increased mortality risk in patients with HF, even in the setting of normal Hb levels.

Iron is involved in many types of metabolism, including oxygen transport in hemoglobin. Iron deficiency (ID), ie a decrease in circulating iron, can have severe consequences. We provide an update on iron metabolism and ID, highlighting the particularities in older adults (OAs). There are three iron compartments in the human body: 1) the functional compartment, which consists of heme proteins including hemoglobin, myoglobin and respiratory enzymes; 2) iron reserves (IR), which consist mainly of liver stocks and are stored as ferritin; and 3) transferrin. There are two types of ID. Absolute ID is characterized by a decrease in IR. Its main pathophysiological mechanism is bleeding, which is often digestive and can be due to neoplasia, frequent in OAs. Biological assessment shows low serum ferritin and transferrin saturation (TS) levels. Furthermore, hypochromic microcytic anemia is frequent, and the serum-soluble transferrin receptor (sTfR) level is high. Functional ID, in which IR are high or normal, is due to inflammation, which is also frequent in OAs, particularly in its chronic form. Biological assessments show high serum ferritin, normal or low TS, and normal sTfR levels. Moreover, C-reactive protein is elevated, and there is moderate non-regenerative non-macrocytic anemia. The main characteristics of iron metabolism anomalies in the elderly are the high frequency of ID (20% of ID with anemia in adults ≥85 years) and the severity of its consequences, which include cognitive impairment in case of ID or iron overload and decrease of physical activity in case of ID. In conclusion, causes of ID are frequently intertwined in OAs as a result of the polymorbidity that characterizes them. ID can have dramatic consequences, especially in frail OAs. Thus, measuring the appropriate biological markers prevents errors in the positive diagnosis of ID type, clarifies etiology, and informs treatment-related decision-making.

Background The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response. Aim We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response. Methods Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 μg once weekly and ribavirin 1,000-1,200 mg/day; 174 were responders. Forty individuals completed treatment with no hemoglobin reduction; 134 developed anemia during therapy. Anemic responders were distributed randomly into two groups: group 1 continued therapy with epoetin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only. Results Patients in group 1 achieved better control of hemoglobin levels (13.8 ± 1.2 g/dl at the end of therapy) than tthose in group 2 (11.5 ± 0.8 g/dl). Sustained virological response was 59.7% in group 1 compared with 34.4% in group 2 (p < 0.01). Conclusions In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment, administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence.

A genome-wide ENU mutagenesis screen in mice was performed to identify novel regulators of erythropoiesis. Here we describe a mouse line, RBC16, which harbours a dominantly inherited mutation in the Cpox gene, responsible for production of the haem biosynthesis enzyme, coproporphyrinogen III oxidase (CPOX). A premature stop codon in place of a tryptophan at amino acid 373 results in reduced mRNA expression and diminished protein levels, yielding a microcytic red cell phenotype in heterozygous mice. Urinary and faecal porphyrins in female RBC16 heterozygotes were significantly elevated compared to that of wildtype littermates, particularly coproporphyrinogen III, while males were biochemically normal. Attempts to induce acute porphyric crises were made using fasting and phenobarbital treatment on females. While fasting had no biochemical effect on RBC16 mice, phenobarbital caused significant elevation of faecal coproporphyrinogen III in heterozygous mice. This is the first known investigation of a mutagenesis mouse model with genetic and biochemical parallels to hereditary coproporphyria.