Heavy metals and trace elements in maternal blood and prevalence of congenital limb abnormalities among newborns: the Japan Environment and Children's Study.

BACKGROUND: Heavy metals such as lead (Pb) and cadmium (Cd) have been associated with adverse pregnancy and developmental outcomes, including congenital abnormalities. This study investigated the association between exposure to heavy metals and trace elements during fetal life and congenital limb abnormalities in infants. METHODS: This study is based on a prospective ongoing nationwide birth cohort from the Japan Environment and Children's Study (JECS). The concentrations of Cd, Pb, mercury (Hg), selenium (Se), and manganese (Mn) were measured in maternal blood collected during the mid-late trimesters. Inclusion criteria were available from questionnaires filled in during pregnancy, including information about congenital limb abnormalities at birth or at one month. To examine the associations with limb anomalies and individual chemicals, logistic regression models were applied following log-transformation or division into quartiles of Cd, Pb, Hg, Se, and Mn concentrations. To assess the associations with the heavy metals and trace elements mixture, quantile g-computation was employed. All models were adjusted for age, maternal smoking history, maternal alcohol intake, history of smoking, and infant sex. RESULTS: Data from 90,163 participants were included in the analysis, of whom 369 had congenital limb abnormalities in any of the collected information, and 89,794 had none. Among the 369 cases of congenital limb abnormalities, there were 185 and 142 cases of polydactyly and syndactyly, respectively. The median concentrations of Pb, Cd, Hg, Se, and Mn were 5.85, 0.66, 3.64, 168, and 15.3 ng/g, respectively. There were no associations between maternal blood concentrations of Pb [adjusted odd ratio = 0.83; 95% confidence interval = 0.61, 1.11], Cd [0.87; 0.68, 1.10], Hg [0.88; 0.73, 1.07], Se [1.07; 0.44, 2.59], and Mn [0.91; 0.64, 1.30] with congenital limb abnormalities. No significant association was observed between the mixture of heavy metals and trace elements [0.85; 0.72, 1.02] and any congenital limb abnormalities. Moreover, there was no association with all polydactylies and all syndactylies, or any type of abnormality as a subdivision. CONCLUSION: At the maternal exposure levels of Cd, Pb, Hg, Se, and Mn assessed in the present study, no association was identified with the risk of developing congenital limb abnormalities in children.

LLL 44 - Module 3: Micronutrients in Chronic disease.

Micronutrients (MN), i.e. trace elements and vitamins, are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). The probability of MN depletion or deficiencies should be considered in all chronic illnesses, especially in those that can interfere with intake, digestion, or intestinal absorption. Low socio-economic status and food deprivation are recognized as the most prevalent reasons for MN deficiencies world-wide. Elderly multimorbid patients with multimodal therapy, as well as patients with long-lasting menu restrictions, are at high risk for both disease related malnutrition as well as multiple MN deficiencies, needing careful specific follow-up. The importance of monitoring MN blood levels along with CRP is essential for optimal care. Drug interactions are also highlighted. In patients with chronic conditions depending on medical nutrition therapy, the provision of adequate dietary reference intakes (DRI) of MN doses and monitoring of their adequacy belongs to standard of care.

Minerals and trace elements in pregnancy in women with previous bariatric surgery consequences on maternal and foetal health.

BACKGROUND: Bariatric surgery (BS) may decrease the risk of these obesity-related complications; however, due to its effect on nutrient intake and absorption, it can also have adverse consequences on maternal and foetal health. The aim of this study is to describe the evolution of electrolytes and trace elements serum levels throughout pregnancy after BS, according to the surgical technique and to evaluate the effect of nutritional deficiencies on the risk of maternal-foetal complications. METHODS: This is a retrospective observational study of the clinical evolution and maternal-foetal complications in a group of women with pregnancies that occurred after BS. Clinical evolution during pregnancy, body weight, and plasma electrolytes, vitamins, and trace elements, as well as their influence on maternal-foetal outcomes were evaluated. Composite neonatal variable (CNV) was defined to evaluate unfavourable foetal outcome. Published reference values for micronutrients during pregnancy have been used. RESULTS: The study includes data on 164 singleton pregnancies in 91 women. A hundred and twenty-seven pregnancies got to full term. The average birth weight was 2966 (546) g., 26.8% < P10 and 13.8% < P3 of a reference population. New-born of gestations after malabsorptive bariatric surgery had a higher risk of having a percentile of birth weight < P3. Plasma electrolytes, trace elements and vitamins throughout pregnancy showed differences depending on the surgical technique, with lower haemoglobin, ferritin, calcium, zinc, copper, vitamin A and vitamin E in the malabsorptive techniques. A high percentage of deficiency was observed, especially in the third trimester (Hb < 11 g/dl: 31.8%; ferritin < 30 mg/ml: 85.7%; zinc < 50 µg/dl: 32.4%, vitamin D < 30 ng/ml: 75.5% and < 20 ng/ml: 53.3%). A decreased plasma copper in the first trimester or zinc in the third trimester were associated with a lower percentile of new-born birth weight. A higher risk of CNV was observed in predominant malabsorptive BS and in pregnancies that had presented at least one vitamin D level lower than 20 ng/ml throughout pregnancy (30.4% vs. 7.1%, p=0.018). CONCLUSIONS: Trace elements and vitamin deficiencies are common in pregnant women after bariatric surgery, especially of iron, zinc, and vitamin D. These deficiencies might negatively affect foetal development. Further studies are needed to better define the role of micronutrients in maternal-foetal health after bariatric surgery.

Dietary inadequacies overestimate the blood deficiencies of magnesium, zinc, and vitamins A, C, E, and D among residents of Sao Paulo.

BACKGROUND & AIMS: We aimed to estimate the prevalence of the inadequate intake and status of magnesium, zinc, and vitamins A, C, E, and D and identify factors associated with micronutrient deficiency in serum/plasma among residents of São Paulo, Brazil. METHODS: Data from 824 individuals aged ≥14 years were obtained from the 2015 ISA-Nutrition, a population-based, cross-sectional survey. Dietary and supplement intakes were assessed using two 24-h dietary recalls, and the micronutrient inadequacies were estimated using the National Cancer Institute method. Micronutrient status was measured in serum or plasma, and deficiency was established according to the lower limit of the reference values. Receiver operating characteristic curve analysis was used to identify the effect of intake on the micronutrient status in serum/plasma. Logistic regression analysis was applied to assess the association between micronutrient status and individual characteristics. RESULTS: More than 80% of the population had an inadequate dietary intake of magnesium, vitamin E, and vitamin D. Males had a high prevalence of inadequate dietary intake of vitamin A and zinc. A high-to-moderate prevalence of inadequate vitamin C intake was observed. Vitamin D was the only nutrient with a deficient status comparable to its dietary inadequacy. The other nutrients demonstrated a lower deficiency prevalence compared to dietary inadequacy, and vitamin A demonstrated the lowest prevalence of deficiency in plasma. Generally, dietary intake showed a non-notable association with micronutrient deficiency in serum/plasma. Individuals with fasting glucose concentrations ≥100 mg/dL and those using diuretic drugs had a higher risk of serum magnesium deficiency. Those using lipid-lowering drugs and those with high plasma adiponectin concentrations had a higher risk of serum zinc deficiency. Individuals who smoked and those with hypertension showed a higher risk of plasma vitamin C deficiency. Individuals with average leptin concentrations had a higher risk of plasma vitamin E deficiency. Finally, those with sufficient leisure-time physical activity had a lower risk of serum vitamin D deficiency. CONCLUSIONS: Residents of the urban areas of São Paulo demonstrated substantially inadequate intakes of most of the assessed micronutrients; however, micronutrient deficiency in serum/plasma was not associated with dietary inadequacy, and it usually demonstrated a lower prevalence than dietary indicators. Thus, using micronutrient intake to determine the serum/plasma profile should be done with caution. The status of the micronutrients varied according to individual characteristics, indicating the interplay of complex mechanisms underlying micronutrient balance.

Enteral zinc supplementation for prevention of morbidity and mortality in preterm neonates.

BACKGROUND: Preterm and low birth weight infants are born with low stores in zinc, which is a vital trace element for growth, cell differentiation and immune function. Preterm infants are at risk of zinc deficiency during the postnatal period of rapid growth. Systematic reviews in the older paediatric population have previously shown that zinc supplementation potentially improves growth and positively influences the course of infectious diseases. In paediatric reviews, the effect of zinc supplementation was most pronounced in those with low nutritional status, which is why the intervention could also benefit preterm infants typically born with low zinc stores and decreased immunity. OBJECTIVES: To determine whether enteral zinc supplementation, compared with placebo or no supplementation, affects important outcomes in preterm infants, including death, neurodevelopment, common morbidities and growth. SEARCH METHODS: Our searches are up-to-date to 20 February 2020. For the first search, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 8), MEDLINE via PubMed (1966 to 29 September 2017), Embase (1980 to 29 September 2017), and CINAHL (1982 to 29 September 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We ran an updated search from 1 January 2017 to 20 February 2020 in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. SELECTION CRITERIA: We included RCTs and quasi-RCTs that compared enteral zinc supplementation versus placebo or no supplementation in preterm infants (gestational age < 37 weeks), and low birth weight babies (birth weight < 2500 grams), at any time during their hospital admission after birth. We included zinc supplementation in any formulation, regimen, or dose administered via the enteral route. We excluded infants who underwent gastrointestinal (GI) surgery during their initial hospital stay, or had a GI malformation or another condition accompanied by abnormal losses of GI juices, which contain high levels of zinc (including, but not limited to, stomas, fistulas, and malabsorptive diarrhoea). DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. Two review authors separately screened abstracts, evaluated trial quality and extracted data. We synthesised effect estimates using risk ratios (RR), risk differences (RD), and standardised mean differences (SMD). Our primary outcomes of interest were all-cause mortality and neurodevelopmental disability. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included five trials with a total of 482 preterm infants; there was one ongoing trial. The five included trials were generally small, but of good methodological quality. Enteral zinc supplementation compared to no zinc supplementation Enteral zinc supplementation started in hospitalised preterm infants may decrease all-cause mortality (between start of intervention and end of follow-up period) (RR 0.55, 95% CI 0.31 to 0.97; 3 studies, 345 infants; low-certainty evidence). No data were available on long-term neurodevelopmental outcomes at 18 to 24 months of (post-term) age. Enteral zinc supplementation may have little or no effect on common morbidities such as bronchopulmonary dysplasia (RR 0.66, 95% CI 0.31 to 1.40, 1 study, 193 infants; low-certainty evidence), retinopathy of prematurity (RR 0.14, 95% CI 0.01 to 2.70, 1 study, 193 infants; low-certainty evidence), bacterial sepsis (RR 1.11, 95% CI 0.60 to 2.04, 2 studies, 293 infants; moderate-certainty evidence), or necrotising enterocolitis (RR 0.08, 95% CI 0.00 to 1.33, 1 study, 193 infants; low-certainty evidence). The intervention probably improves weight gain (SMD 0.46, 95% CI 0.28 to 0.64; 5 studies, 481 infants; moderate-certainty evidence); and may slightly improve linear growth (SMD 0.75, 95% CI 0.36 to 1.14, 3 studies, 289 infants; low-certainty evidence), but may have little or no effect on head growth (SMD 0.21, 95% CI -0.02 to 0.44, 3 studies, 289 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Enteral supplementation of zinc in preterm infants compared to no supplementation or placebo may moderately decrease mortality and probably improve short-term weight gain and linear growth, but may have little or no effect on common morbidities of prematurity. There are no data to assess the effect of zinc supplementation on long-term neurodevelopment.

Essentiality of Trace Elements in Pregnancy, Fertility, and Gynecologic Cancers-A State-of-the-Art Review.

Gynecological neoplasms pose a serious threat to women's health. It is estimated that in 2020, there were nearly 1.3 million new cases worldwide, from which almost 50% ended in death. The most commonly diagnosed are cervical and endometrial cancers; when it comes to infertility, it affects ~48.5 million couples worldwide and the number is continually rising. Ageing of the population, environmental factors such as dietary habits, environmental pollutants and increasing prevalence of risk factors may affect the reproductive potential in women. Therefore, in order to identify potential risk factors for these issues, attention has been drawn to trace elements. Trace mineral imbalances can be caused by a variety of causes, starting with hereditary diseases, finishing with an incorrect diet or exposure to polluted air or water. In this review, we aimed to summarize the current knowledge regarding trace elements imbalances in the case of gynecologic cancers as well as female fertility and during pregnancy.

Long-term iodine nutrition is associated with longevity in older adults: a 20 years' follow-up of the Randers-Skagen study.

Iodine intake affects the occurrence of thyroid disorders. However, the association of iodine intake with longevity remains to be described. This led us to perform a 20 years' follow-up on participants from the Randers-Skagen (RaSk) study. Residents in Randers born in 1920 (n 210) and Skagen born in 1918-1923 (n 218) were included in a clinical study in 1997-1998. Mean iodine content in drinking water was 2 µg/l in Randers and 139 µg/l in Skagen. We collected baseline data through questionnaires, performed physical examinations and measured iodine concentrations in spot urine samples. Income data were retrieved from Danish registries. We performed follow-up on mortality until 31 December 2017 using Danish registries. Complete follow-up data were available on 428 out of 430 of participants (99·5 %). At baseline, the median urinary iodine concentration was 55 µg/l in Randers and 160 µg/l in Skagen residents. Participants were long-term residents with 72·8 and 92·7 % residing for more than 25 years in Randers and Skagen, respectively. Cox regression showed that living in Skagen compared with Randers was associated with a lower hazard ratio (HR) of death in both age- and sex-adjusted analyses (HR 0·60, 95 % CI 0·41, 0·87, P = 0·006), but also after adjustment for age, sex, number of drugs, Charlson co-morbidity index, smoking, alcohol and income (HR 0·60, 95 % CI 0·41, 0·87, P = 0·008). Residing in iodine-replete Skagen was associated with increased longevity. This indicates that long-term residency in an iodine-replete environment may be associated with increased longevity compared with residency in an iodine-deficient environment.

Recent insights into trace element deficiencies: causes, recognition and correction.

PURPOSE OF REVIEW: Trace elements are vital components involved in major body functions. Cases of trace elements deficiencies are increasingly encountered in clinical practice, although often underrecognized. This review gives a thorough insight into the newest findings on clinical situations associated with trace elements deficiencies in children and adults, their recognition and management. RECENT FINDINGS: Trace elements deficiencies are frequently found in various conditions, most commonly in burns, bariatric surgery, intestinal failure, renal replacement therapy, oncology, critical illness and cardiac surgery. The main trace elements involved are selenium, zinc, copper and iron. Trace elements deficiencies are associated with increased risk of morbidity and mortality. Recognition of clinical signs of trace elements deficiencies can be challenging. Although trace elements supplementation is indisputable in many circumstances, it is still debatable in other situations such as sepsis and cardiac surgery. SUMMARY: Recent findings on trace elements deficiencies could have important implications on health outcomes. Trace elements delivery is a core component of nutritional care. Front-line clinicians should be aware of at-risk clinical situations to provide correct and timely intervention. Future research should be directed towards investigating the potential benefits of antioxidant trace elements supplementation in children in whom studies are scarce, especially in critical conditions such as burns, sepsis and cardiac surgery.

The other view: the trace element selenium as a micronutrient in thyroid disease, diabetes, and beyond.

Antibiotics are provided for infections caused by bacteria, and statins help to control hypercholesterolemia. When hungry, you need to eat, and when you are deficient in a particular nutrient, the diet should be chosen wisely to provide what is missing. In the matter of providing the essential trace element selenium (Se), there are two different but partly overlapping views on its nature and requirements. Some consider it a medication that should be given to a subset of more or less well-defined (thyroid) patients only, in order to alleviate symptoms, to improve the course of the disease or even to provide a cure, alone or in an adjuvant mode. Such treatment attempts are conducted for a short time period, and potential medical benefits and side effects are evaluated thoroughly. One could also approach Se in medicine in a more holistic way and evaluate primarily the nutritional status of the patient before considering supplementation. The available evidence for positive health effects of supplemental Se can be interpreted as the consequence of correcting deficiency instead of speculating on a direct pharmaceutical action. This short review provides a novel view on Se in (thyroid) disease and beyond and offers an alternative explanation for its positive health effects, i.e., its provision of the substrate needed for allowing adequate endogenous expression of those selenoproteins that are required in certain conditions. In Se deficiency, the lack of the trace element constitutes the main limitation for the required adaptation of selenoprotein expression to counteract health risks and alleviate disease symptoms. Supplemental Se lifts this restriction and enables the full endogenous response of selenoprotein expression. However, since Se does not act as a pharmacological medication per se, it should not be viewed as a dangerous drug, and, importantly, current data show that supplemental Se does not cause diabetes.

Zinc Deficiency Activates the IL-23/Th17 Axis to Aggravate Experimental Colitis in Mice.

BACKGROUND AND AIMS: Patients with inflammatory bowel disease [IBD], especially Crohn's disease, often develop zinc deficiency. However, the precise mechanisms by which zinc deficiency affects IBD pathology, particularly intestinal macrophage function, remain unclear. We studied the effects of zinc deficiency on the development and progression of colitis in mice. METHODS: To induce colitis, mice were treated with 2,4,6-trinitrobenzene sulphonic acid. Rag1-/- mice were then given injections of naïve CD4+CD62L+ T cells. The respective degrees of mucosal injury of mice that had received a zinc chelator (TPEN; N,N,N',N'-tetrakis [2-pyridylmethyl]ethylenediamine) and of control mice were subsequently compared. Colonic lamina propria mononuclear cells were isolated by enzymatic digestion and were examined using flow cytometry. To generate mouse bone marrow-derived macrophages [BMDMs], bone marrow cells were stimulated with mouse macrophage-colony stimulating factor. RESULTS: Zinc deficiency aggravates colonic inflammation through the activation of type 17 helper T [Th17] cells in mice. Flow cytometric analysis revealed that zinc deficiency significantly increases the proportion of pro-inflammatory [M1] macrophages in colonic lamina propria mononuclear cells obtained from inflamed colon. Interferon-γ plus lipopolysaccharide-mediated M1 skewing alters the expression of zinc transporters in BMDMs and thereby decreases the intracellular free zinc. TPEN treatment mimicking the effects of the M1 skewing up-regulates IL-23p19 expression, which is strongly related to Th17 development. Furthermore, the nuclear accumulation of interferon-regulatory factor 5 is closely involved in IL-23p19 induction in zinc-deficient macrophages. CONCLUSIONS: Zinc deficiency aggravates colonic inflammation through activation of the IL-23/Th17 axis. This activation is controlled by subcellular distribution of interferon-regulatory factor 5.

Micronutrient Deficiencies in Children With Inflammatory Bowel Diseases.

BACKGROUND: Children with inflammatory bowel diseases (IBDs) are at risk of developing nutrition deficiencies, particularly because of reduced intake, restrictive diets, malabsorption, and excessive nutrient loss. In this study, we aimed to assess the status of trace elements, minerals, and vitamins in a large cohort of children with IBDs. METHODS: Medical records of children diagnosed with IBDs during 2000-2016 were reviewed retrospectively. Retrieved data included demographics, disease characteristics, disease activity indices, anthropometric measures, and specific trace elements, minerals, and vitamins at diagnosis and during follow-up. RESULTS: Out of 359 children with IBD (158 [44%] females, median age at diagnosis 14.1 years, interquartile range [IQR] 12.0-16.0), 240 (67%) were diagnosed with Crohn's disease (CD) and 119 (33%) with ulcerative colitis (UC). Median follow-up time was 7 years (IQR 5-10). The prevalence of deficiencies in patients with CD at diagnosis and last follow-up, respectively, were iron (88% and 39.5%), zinc (53% and 11.5%), vitamin D (39% and 36%), and folic acid (10% and 13%). In patients with UC, frequencies were: iron (77% and 40%), vitamin D (49% and 33%), zinc (31% and 10%), and folic acid (3.8% and 9.7%). Magnesium and vitamin B12 deficiencies were rare. For both diseases, iron deficiency was associated with hypoalbuminemia. Deficiencies in iron and zinc were more common in patients with CD than those with UC. CONCLUSIONS: Deficiencies in iron, zinc, and vitamin D are common at pediatric IBD diagnosis with limited improvement during follow-up, whereas deficiencies in magnesium and vitamin B12 are rare.

Increased Needs for Copper in Parenteral Nutrition for Children in the Neonatal Intensive Care Unit With an Ostomy.

BACKGROUND: Copper (Cu) is an essential trace element, with deficiency causing anemia, neutropenia, and other abnormalities. Cu is mainly absorbed in the small intestine. Patients with intestinal failure or jejunostomy have increased Cu losses and require additional Cu supplementation in parenteral nutrition (PN). The American Society for Clinical Nutrition standards for trace element recommendations in PN, including Cu, were created in 1988, and the American Society for Parenteral and Enteral Nutrition currently follows the same recommendations. METHODS: Patients admitted to the neonatal intensive care unit for surgical intervention resulting in an ostomy (ileal or jejunal) were included in this retrospective study. Patients received PN support with Cu dosed individually, rather than in a multi-trace element package. Cu and ostomy output were analyzed daily. Serum Cu was obtained 2 months postsurgical intervention. RESULTS: Out of the 7 patients enrolled, 71% had low serum Cu. Weekly mean Cu intake for all 7 patients ranged from 5.3 to 154.8 µg/kg/day from enteral and parenteral sources, with individual mean weekly Cu intake ranging from 18.9 to 74.4 µg/kg/day from surgical intervention to 2 months post-surgery. Patients' weekly ostomy outputs ranged from 0 mL/kg/day to 77.2 mL/kg/day, with individual mean weekly output ranging from 3.7 to 41.6 mL/kg/day. CONCLUSION: Providing 20 µg/kg/day of Cu in PN to neonates with ostomies is insufficient to prevent Cu deficiency. Further studies are warranted to determine an optimal dosage of parenteral Cu to prevent Cu deficiency.

Micronutrient Depletion in Heart Failure: Common, Clinically Relevant and Treatable.

Heart failure (HF) is a chronic condition with many imbalances, including nutritional issues. Next to sarcopenia and cachexia which are clinically evident, micronutrient deficiency is also present in HF. It is involved in HF pathophysiology and has prognostic implications. In general, most widely known micronutrients are depleted in HF, which is associated with symptoms and adverse outcomes. Nutritional intake is important but is not the only factor reducing the micronutrient availability for bodily processes, because absorption, distribution, and patient comorbidity may play a major role. In this context, interventional studies with parenteral micronutrient supplementation provide evidence that normalization of micronutrients is associated with improvement in physical performance and quality of life. Outcome studies are underway and should be reported in the following years.

Iron loading and secondary multi-trace element deficiency in a dairy herd fed silage grass grown on land fertilized with sewage sludge.

Recycling sewage sludge by applying it to agricultural land is strategically important in the European Union and is regulated by Directive 86/278/EEC, aimed at protecting the soil and humans from the presence of unwanted substances. However, because of the ruminant feeding habits, there is a risk that animals grazed on pasture or fed crops grown on land treated in this way may ingest biosolids adhered to foliage and/or on the top soil. This paper describes an episode of toxicity in a dairy herd consuming silage from a field fertilized with sewage sludge produced in a wastewater treatment plant. The affected cows were recumbent, unable to rise and suffered diarrhoea. Analysis of tissues (fresh weight) from a cow that subsequently died revealed severe hepatic iron loading (6720 mg/kg) and secondary multi-trace element hepatic deficiency, particularly of copper (0.812 mg/kg) and manganese (0.436 mg/kg), but also selenium (0.164 mg/kg) and zinc (19.9 mg/kg). The study findings indicate that the use of sewage sludge in agriculture can cause secondary multi-trace element deficiencies in ruminants. Careful attention should be taken when crops are ensilaged avoiding top-soil sewage sludge contamination, since the acidification process may greatly increase Fe bioavailability.

Multifactorial Etiology of Anemia in Celiac Disease and Effect of Gluten-Free Diet: A Comprehensive Review.

Celiac disease (CD) is a multisystemic disorder with different clinical expressions, from malabsorption with diarrhea, anemia, and nutritional compromise to extraintestinal manifestations. Anemia might be the only clinical expression of the disease, and iron deficiency anemia is considered one of the most frequent extraintestinal clinical manifestations of CD. Therefore, CD should be suspected in the presence of anemia without a known etiology. Assessment of tissue anti-transglutaminase and anti-endomysial antibodies are indicated in these cases and, if positive, digestive endoscopy and intestinal biopsy should be performed. Anemia in CD has a multifactorial pathogenesis and, although it is frequently a consequence of iron deficiency, it can be caused by deficiencies of folate or vitamin B12, or by blood loss or by its association with inflammatory bowel disease (IBD) or other associated diseases. The association between CD and IBD should be considered during anemia treatment in patients with IBD, because the similarity of symptoms could delay the diagnosis. Vitamin B12 deficiency is common in CD and may be responsible for anemia and peripheral myeloneuropathy. Folate deficiency is a well-known cause of anemia in adults, but there is little information in children with CD; it is still unknown if anemia is a symptom of the most typical CD in adult patients either by predisposition due to the fact of age or because biochemical and clinical manifestations take longer to appear.

Copper Deficiency: Causes, Manifestations, and Treatment.

BACKGROUND: The metabolism of the essential trace element copper remains incompletely understood and, until recently, nearly ignored in acute medicine. Menkes disease was for long the only known copper deficiency condition, but several case reports and investigations conducted over the last 2 decades have shown that deficiency is more frequent than previously suspected, with devastating individual consequences and potential public health consequences. The copper needs in healthy individuals are 0.9 mg/d, which translates to 0.3 mg/d intravenously in parenteral nutrition; the present review aims at gathering actual knowledge. METHOD AND RESULTS: A review of literature was conducted in PubMed and Cochrane systematic reviews to identify the most recent information about copper deficiency and generate a narrative review. Copper deficiency has hereditary and acquired origins, the latter being the most frequent. Clinical manifestations are nonspecific but affect all organs and systems, particularly the hematologic (anemia) and the neurologic (myeloneuropathy) systems. Deficiency also affects the cardiovascular, cutaneous, and immune systems. Severe copper deficiency due to reduced absorption after bariatric bypass surgery has become frequent. CONCLUSION: Deficiency is more frequent than previously recognized, probably because of changing nutrition patterns but also because of some treatments that have become very common such as bypass bariatric surgery and, in acute medicine, prolonged continuous renal replacement therapy. The patients may present with severe hematologic and neurologic complications that go untreated because copper deficiency was not considered in the differential diagnosis: These complications often need active intravenous repletion with doses 4-8 times the usual nutrition recommendations.

Selenium in Cardiac Surgery.

Selenium (Se) is an essential trace element that plays a pivotal role in many of the body's regulatory and metabolic functions, especially during times of stress. After uptake, Se is incorporated into several Se-dependent proteins, which have potent anti-inflammatory and antioxidant capacities. Several observational clinical studies have demonstrated that Se deficiency can cause chronic cardiovascular diseases and aggravate organ dysfunction after cardiac surgery and that low levels of Se may be independently associated with the development of organ dysfunction after cardiac surgery. Based on these findings, several studies have investigated the effects of a perioperative Se supplementation strategy. Therefore, the present review describes in depth the pathophysiology and harmful stimuli during cardiac surgery, how Se may counteract these injuries, the different types of Se supplementation strategies that have been evaluated, and current evidence of its clinical significance.

Nutritional and vitamin status in patients with neuroendocrine neoplasms.

Symptoms of gastroenteropancreatic located neuroendocrine neoplasms (GEP-NENs) are often related to food intake and manifest as abdominal pain or diarrhoea which can influence patients nutritional status. Malnutrition is common in cancer patients and influences quality of life, treatment options and survival but is also present in up to 40% of patients with GEP-NENs. As part of malnutrition there are often deficiencies in fat-soluble vitamins, mainly vitamin D. Little knowledge exists on trace elements. Several factors influence the development of malnutrition such as size and localisation of the primary tumour as well as metastases, side effects from treatment but also hormone production of the tumour itself. One of the main influencing factors leading to malnutrition is diarrhoea which leads to dehydration and electrolyte disturbances. Treatment of diarrhoea should be guided by its cause. Screening for malnutrition should be part of routine care in every GEP-NEN patient. Multidisciplinary treatment including dietician support is necessary for all malnourished patients with GEP-NENs.

Arsenic-induced cardiotoxicity correlates with mitochondrial damage and trace elements imbalance in broiler chickens.

Arsenic-based drugs as food additive were used in poultry. However, excessive arsenic exposure can disturb myocardial cell metabolism, which results in the inhibition of growth and development of chickens. Since disordered mitochondria influences cardiac physiology and pathology, a better understanding of the mechanisms modulating cardiomyocyte mitochondria process is critical for identifying the potent detoxication targets under arsenic exposure in chickens. Male Hy-line chickens (1-day-old) were fed either a basal diet or an arsenic trioxide (As2O3)-supplemented diet containing 7.5, 15, and 30 mg/kg As2O3 for 90 d. The concentrations of ions ([Na, Mg, Al, Si, K, Ca, As, Mn, Fe, Zn] and [Cr, Ni, Cu, Ba]) significantly increased and decreased in the heart of chicken under As2O3 exposure, respectively. Moreover, we observed that As2O3 decreased high-density lipoprotein cholesterol concentrations and increased total cholesterol concentrations in the serum. We also observed arterial wall degeneration, biochemical character of mitochondria undergoing either fission or fusion, typical apoptotic cells, typical DNA fragments and TdT-mediated dUTP nick end labeling positive nuclei under As2O3 exposure in the heart. Further quantitative real-time PCR demonstrated that B cell lymphoma/leukemia 2 (Bcl2) were significantly decreased and dynamin-related protein 1 (Drp1), Optic atrophy 1 (Opa1), mitochondrial fission factor 1 (Mfn1), Mfn2, p53, caspase-8, Bcl-2 associated X protein (Bax), caspase-3, caspase-9 and cytochrome C were significantly increased in all As2O3 group. In conclusion, As2O3 can disturb the trace elements homeostasis, which might favor the development of mitochondrial damage. Moreover, we suspected that As2O3-increased mitochondrial dynamics might trigger the apoptosis to limit cell metabolism. These features might identify the role of the mitochondrial dynamics under arsenic-induced cardiovascular disease in the chickens.