Current concepts in postpartum anemia management.

PURPOSE OF REVIEW: Postpartum anemia (PPA) is common in women after childbirth and affects about 50-80% of all women worldwide. Iron deficiency (ID) is the main cause for anemia and constitutes a potentially preventable condition with great impact on the mother's physical and mental condition after delivery. In most cases, PPA is associated with antenatal ID and peripartum blood losses. Numerous published studies confirmed the positive effect of PPA diagnosis and treatment. RECENT FINDINGS: Iron deficiency as well as iron deficiency anemia (IDA) are common in the postpartum period and represent significant health problems in women of reproductive age. SUMMARY: Important movements towards early detection and therapy of postpartum anemia have been observed. However, postpartum anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Diagnosis and therapy of PPA, particularly iron supplementation in ID and IDA, has proven to be highly effective with a tremendous effect on women's wellbeing and outcome.

Reported outcomes in patients with iron deficiency or iron deficiency anemia undergoing major surgery: a systematic review of outcomes.

BACKGROUND: Iron deficiency (ID) is the leading cause of anemia worldwide. The prevalence of preoperative ID ranges from 23 to 33%. Preoperative anemia is associated with worse outcomes, making it important to diagnose and treat ID before elective surgery. Several studies indicated the effectiveness of intravenous iron supplementation in iron deficiency with or without anemia (ID(A)). However, it remains challenging to establish reliable evidence due to heterogeneity in utilized study outcomes. The development of a core outcome set (COS) can help to reduce this heterogeneity by proposing a minimal set of meaningful and standardized outcomes. The aim of our systematic review was to identify and assess outcomes reported in randomized controlled trials (RCTs) and observational studies investigating iron supplementation in iron-deficient patients with or without anemia. METHODS: We searched MEDLINE, CENTRAL, and ClinicalTrials.gov systematically from 2000 to April 1, 2022. RCTs and observational studies investigating iron supplementation in patients with a preoperative diagnosis of ID(A), were included. Study characteristics and reported outcomes were extracted. Outcomes were categorized according to an established outcome taxonomy. Quality of outcome reporting was assessed with a pre-specified tool. Reported clinically relevant differences for sample size calculation were extracted. RESULTS: Out of 2898 records, 346 underwent full-text screening and 13 studies (five RCTs, eight observational studies) with sufficient diagnostic inclusion criteria for iron deficiency with or without anemia (ID(A)) were eligible. It is noteworthy to mention that 49 studies were excluded due to no confirmed diagnosis of ID(A). Overall, 111 outcomes were structured into five core areas including nine domains. Most studies (92%) reported outcomes within the 'blood and lymphatic system' domain, followed by "adverse event" (77%) and "need for further resources" (77%). All of the latter reported on the need for blood transfusion. Reported outcomes were heterogeneous in measures and timing. Merely, two (33%) of six prospective studies were registered prospectively of which one (17%) showed no signs of selective outcome reporting. CONCLUSION: This systematic review comprehensively depicts the heterogeneity of reported outcomes in studies investigating iron supplementation in ID(A) patients regarding exact definitions and timing. Our analysis provides a systematic base for consenting to a minimal COS. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020214247.

Identifying a target group for selenium supplementation in high-risk cardiac surgery: a secondary analysis of the SUSTAIN CSX trial.

BACKGROUND: Recent data from the randomized SUSTAIN CSX trial could not confirm clinical benefits from perioperative selenium treatment in high-risk cardiac surgery patients. Underlying reasons may involve inadequate biosynthesis of glutathione peroxidase (GPx3), which is a key mediator of selenium's antioxidant effects. This secondary analysis aimed to identify patients with an increase in GPx3 activity following selenium treatment. We hypothesize that these responders might benefit from perioperative selenium treatment. METHODS: Patients were selected based on the availability of selenium biomarker information. Four subgroups were defined according to the patient's baseline status, including those with normal kidney function, reduced kidney function, selenium deficiency, and submaximal GPx3 activity. RESULTS: Two hundred and forty-four patients were included in this analysis. Overall, higher serum concentrations of selenium, selenoprotein P (SELENOP) and GPx3 were correlated with less organ injury. GPx3 activity at baseline was predictive of 6-month survival (AUC 0.73; p = 0.03). While selenium treatment elevated serum selenium and SELENOP concentrations but not GPx3 activity in the full patient cohort, subgroup analyses revealed that GPx3 activity increased in patients with reduced kidney function, selenium deficiency and low to moderate GPx3 activity. Clinical outcomes did not vary between selenium treatment and placebo in any of these subgroups, though the study was not powered to conclusively detect differences in outcomes. CONCLUSIONS: The identification of GPx3 responders encourages further refined investigations into the treatment effects of selenium in high-risk cardiac surgery patients.

Penny-wise and pound-foolish: the challenges of preoperative anaemia management.

The timely correction of anaemia before major surgery is important for optimising perioperative patient outcomes. However, multiple barriers have precluded the global expansion of preoperative anaemia treatment programmes, including misconceptions about the true cost/benefit ratio for patient care and health system economics. Institutional investment and buy-in from stakeholders could lead to significant cost savings through avoided complications of anaemia and red blood cell transfusions, and through containment of direct and variable costs of blood bank laboratories. In some health systems, billing for iron infusions could generate revenue and promote growth of treatment programmes. The aim of this work is to galvanise integrated health systems worldwide to diagnose and treat anaemia before major surgery.

Current practices in nutrition therapy in cardiac surgery patients: An international multicenter observational study.

BACKGROUND: Cardiac surgery patients with a prolonged stay in the intensive care unit (ICU) are at high risk for acquired malnutrition. Medical nutrition therapy practices for cardiac surgery patients are unknown. The objective of this study is to describe the current nutrition practices in critically ill cardiac surgery patients worldwide. METHODS: We conducted a prospective observational study in 13 international ICUs involving mechanically ventilated cardiac surgery patients with an ICU stay of at least 72 h. Collected data included the energy and protein prescription, type of and time to the initiation of nutrition, and actual quantity of energy and protein delivered (maximum: 12 days). RESULTS: Among 237 enrolled patients, enteral nutrition (EN) was started, on average, 45 h after ICU admission (range, 0-277 h; site average, 53 [range, 10-79 h]). EN was prescribed for 187 (79%) patients and combined EN and parenteral nutrition in 33 (14%). Overall, patients received 44.2% (0.0%-117.2%) of the prescribed energy and 39.7% (0.0%-122.8%) of the prescribed protein. At a site level, the average nutrition adequacy was 47.5% (30.5%-78.6%) for energy and 43.6% (21.7%-76.6%) for protein received from all nutrition sources. CONCLUSION: Critically ill cardiac surgery patients with prolonged ICU stay experience significant delays in starting EN and receive low levels of energy and protein. There exists tremendous variability in site performance, whereas achieving optimal nutrition performance is doable.

Is a Patient Blood Management programme economically reasonable?

PURPOSE OF REVIEW: The value of healthcare is defined as the achieved health outcome in relation to the incurred costs. Patient Blood Management (PBM) is a multidisciplinary, evidence-based and patient-centred concept to optimize the patients' red blood cell mass, minimize blood loss and bleeding and to secure the physiological reserve, including the promotion of evidence-based transfusion strategies. This review describes the healthcare value and the cost effectiveness of single PBM measures as well as the implementation of comprehensive PBM programmes. RECENT FINDINGS: Overall, measures improving surgical outcome and reducing hospital length of stay, such as intravenous iron supplementation in iron deficient anaemic patients, the use of antifibrinolytic agents for the treatment of bleeding, the use of cell salvage and adherence to an evidence-based transfusion strategy, are associated with cost savings. SUMMARY: Although several single PBM measures have been shown to be effective and cost-efficient, it remains challenging to compare the results among differing healthcare systems.

Current concepts in preoperative anemia management in obstetrics.

PURPOSE OF REVIEW: The purpose of this article is to provide an overview of currently recommended treatment approaches for anemia during pregnancy, with a special focus on iron deficiency and iron deficiency anemia (IDA). RECENT FINDINGS: As consistent patient blood management (PBM) guidelines in obstetrics are still lacking, recommendations regarding the timing of anemia screening and the treatment recommendations for iron deficiency and IDA during pregnancy are still controversial. Based on increasing evidence, early screening for anemia and iron deficiency should be recommended at the beginning of each pregnancy. To reduce maternal and fetal burden, any iron deficiency, even without anemia, should be treated as early as possible during pregnancy. While oral iron supplements administered every other day are the standard treatment in the first trimester, the use of intravenous iron supplements is increasingly suggested from the second trimester onwards. SUMMARY: The treatment of anemia, and more specifically iron deficiency anemia during pregnancy, holds many possibilities for improvement. The fact that the period of risk is known well in advance and thus there is a long optimization phase is per se an ideal prerequisite for the best possible therapy of treatable causes of anemia. Standardization of recommendations and guidelines for screening and treatment of IDA in obstetrics is required for the future. In any case, a multidisciplinary consent is the precondition for a successfully implementation of anemia management in obstetrics to establish an approved algorithm easily enabling detection and treatment of IDA during pregnancy.

Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients: The SUSTAIN CSX Randomized Clinical Trial.

Importance: Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery. Objective: To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients. Design, Setting, and Participants: This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized. Interventions: Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 µg/L of sodium selenite prior to cardiopulmonary bypass, 2000 µg/L immediately postoperatively, and 1000 µg/L each day in intensive care for a maximum of 10 days or placebo. Main Outcomes and Measures: The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery. Results: A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups. Conclusions and Relevance: In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT02002247.

Medical nutrition therapy in patients receiving ECMO: Evidence-based guidance for clinical practice.

Patients receiving extracorporeal membrane oxygenation (ECMO) inherit substantial disease-associated metabolic, endocrinologic, and immunologic modifications. Along with the technical components of ECMO, the aforementioned alterations may affect patients' needs and feasibility of adequate macronutrient and micronutrient supply and intake. Thus, patients receiving ECMO are at increased risk for iatrogenic malnutrition and require targeted individual medical nutrition therapy (MNT). However, specific recommendations for MNT in patients receiving ECMO are limited and, with some exceptions, based on an evidence base encompassing general patients who are critically ill. Consequently, clinician decision-making for MNT in patients receiving ECMO is unguided, which may further increase nutrition risk, culminating in iatrogenic malnutrition and ultimately affecting patient outcomes. The purpose of this article is to provide educational background and highlight specific points for MNT in adult patients receiving ECMO, which might serve as evidence-based guidance to develop institutional standard operating procedures and nutrition protocols for daily clinical practice.

Pharmacokinetics of Phenprocoumon in Emergency Situations-Results of the Prospective Observational RADOA-Registry (Reversal Agent Use in Patients Treated with Direct Oral Anticoagulants or Vitamin K Antagonists Registry).

Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings (n = 82) and with urgent surgery (n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.

Adverse events of iron and/or erythropoiesis-stimulating agent therapy in preoperatively anemic elective surgery patients: a systematic review.

BACKGROUND: Iron supplementation and erythropoiesis-stimulating agent (ESA) administration represent the hallmark therapies in preoperative anemia treatment, as reflected in a set of evidence-based treatment recommendations made during the 2018 International Consensus Conference on Patient Blood Management. However, little is known about the safety of these therapies. This systematic review investigated the occurrence of adverse events (AEs) during or after treatment with iron and/or ESAs. METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Transfusion Evidence Library, Web of Science) and two trial registries (ClinicalTrials.gov, WHO ICTRP) were searched until 23 May 2022. Randomized controlled trials (RCTs), cohort, and case-control studies investigating any AE during or after iron and/or ESA administration in adult elective surgery patients with preoperative anemia were eligible for inclusion and judged using the Cochrane Risk of Bias tools. The GRADE approach was used to assess the overall certainty of evidence. RESULTS: Data from 26 RCTs and 16 cohort studies involving a total of 6062 patients were extracted, on 6 treatment comparisons: (1) intravenous (IV) versus oral iron, (2) IV iron versus usual care/no iron, (3) IV ferric carboxymaltose versus IV iron sucrose, (4) ESA+iron versus control (placebo and/or iron, no treatment), (5) ESA+IV iron versus ESA+oral iron, and (6) ESA+IV iron versus ESA+IV iron (different ESA dosing regimens). Most AE data concerned mortality/survival (n=24 studies), thromboembolic (n=22), infectious (n=20), cardiovascular (n=19) and gastrointestinal (n=14) AEs. Very low certainty evidence was assigned to all but one outcome category. This uncertainty results from both the low quantity and quality of AE data due to the high risk of bias caused by limitations in the study design, data collection, and reporting. CONCLUSIONS: It remains unclear if ESA and/or iron therapy is associated with AEs in preoperatively anemic elective surgery patients. Future trial investigators should pay more attention to the systematic collection, measurement, documentation, and reporting of AE data.

Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials.

BACKGROUND: The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration. METHODS: Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials. RESULTS: Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62-0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference - 3.13 days, 95% CI - 5.36 to - 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference - 5.07 days, 95% CI - 7.42 to - 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels. CONCLUSIONS: Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results. TRIAL REGISTRATION: PROSPERO international prospective database of systematic reviews (CRD42021256939-05 July 2021).

The impact of intravenous iron supplementation in elderly patients undergoing major surgery.

BACKGROUND: Age and preoperative anaemia are risk factors for poor surgical outcome and blood transfusion. The aim of this study was to examine the effect of iron supplementation in iron-deficient (ID) elderly patients undergoing major surgery. METHOD: In this single-centre observational study, patients ≥ 65 years undergoing major surgery were screened for anaemia and ID. Patients were assigned to the following groups: A- (no anaemia); A-,ID+,T+ (no anaemia, iron-deficient, intravenous iron supplementation); A+ (anaemia); and A+,ID+,T+ (anaemia, iron-deficient, intravenous iron supplementation). RESULTS: Of 4,381 patients screened at the anaemia walk-in clinic, 2,381 (54%) patients were ≥ 65 years old and 2,191 cases were included in analysis. The ID prevalence was 63% in patients with haemoglobin (Hb) < 8 g/dl, 47.2% in patients with Hb from 8.0 to 8.9 g/dl, and 44.3% in patients with Hb from 9 to 9.9 g/dl. In severely anaemic patients, an Hb increase of 0.6 (0.4; 1.2) and 1.2 (0.7; 1.6) g/dl was detected with iron supplementation 6-10 and > 10 days before surgery, respectively. Hb increased by 0 (-0.1; 0) g/dl with iron supplementation 1-5 days before surgery, 0.2 (-0.1; 0.5) g/dl with iron supplementation 6-10 days before surgery, and 0.2 (-0.2; 1.1) g/dl with supplementation > 10 days before surgery (p < 0.001 for 1-5 vs. 6-10 days). Overall, 58% of A+,ID+,T+ patients showed an Hb increase of > 0.5 g/dl. The number of transfused red blood cell units was significantly lower in patients supplemented with iron (0 (0; 3)) compared to non-treated anaemic patients (1 (0; 4)) (p = 0.03). Patients with iron supplementation > 6 days before surgery achieved mobility 2 days earlier than patients with iron supplementation < 6 days. CONCLUSIONS: Intravenous iron supplementation increases Hb level and thereby reduces blood transfusion rate in elderly surgical patients with ID anaemia.

[Preoperative anemia in patients with rheumatic diseases]. / Präoperative Anämie beim Rheumatiker.

A preoperative anemia is an independent risk factor for the occurrence of complications during and after surgical interventions. It is associated with an increased length of hospital stay, higher mortality and an increased use of blood transfusions. Anemia affects some 30-70% of patients suffering from inflammatory rheumatic diseases, mostly caused by iron deficiency and/or chronic inflammation. The possibilities to treat anemia in rheumatic patients were extremely limited for a long period of time as older studies showed life-threatening side effects, the need of high doses of iron supplements or the occurrence of many nonresponders. Further development of the supplements, new dosage schemes and the combination of supplements increased the efficacy and reduced the occurrence of side effects to a minimum. In addition to orthopedic surgical interventions for rheumatism that despite new therapeutic options in some cases still represent the only way to alleviate the complaints, more and more patients with inflammatory rheumatic diseases also need surgical interventions due to comorbidities. Therefore, anemia should be clarified and preoperatively treated in accordance with the new study situation, to minimize additional complications due to anemia and to increase patient safety.

The impact of timing of intravenous iron supplementation on preoperative haemoglobin in patients scheduled for major surgery.

BACKGROUND: Anaemia is frequent and an independent risk factor for morbidity and mortality in patients undergoing surgery. Iron deficiency (ID) is the main cause for anaemia and can be corrected by intravenous (IV) iron. The aim of this study was to investigate the timing of preoperative IV iron supplementation on preoperative haemoglobin (Hb) level. MATERIALS AND METHODS: Surgical patients were screened for the presence of anaemia and ID from November 2015 to January 2020. In case of ID or iron deficiency anaemia (IDA), patients received IV iron supplementation. The timing of IV iron supplementation on preoperative Hb level was analysed by days and time frames clustered by 5 days before surgery. RESULTS: In total, 404 patients with IV iron supplementation were analysed. In all patients, IV iron was administered with a median (interquartile range [IQR]) of 3.0 (1.0; 9.0) days before surgery. Preoperative Hb level increased steadily starting from 6 days (0.13 [±1.2] g/dL) until 16 days before surgery (1.75 [±1.1] g/dL). Group comparison revealed a median preoperative Hb change of -0.2 (-0.5; 0.2) g/dL for days 1-5, 0.2 (0.0; 0.7) g/dL for days 6-10, 0.7 (0.2; 1.1) g/dL for days 11-15, 0.7 (0.2; 1.8) g/dL for days 16-20, 0.9 (0.3; 1.7) g/dL for days 21-25, 1.5 (0.4; 2.6) g/dL for days 26-30, and 0.6 (0.0; 1.7) g/dL for >31 days. Three patients received multiple administrations of IV iron which resulted in an increase in Hb of >4 g/dL. DISCUSSION: Supplementation of IV iron to increase Hb concentration preoperatively may be most effective if administered at least ten days before surgery.

Vitamin D deficiency in critically ill COVID-19 ARDS patients.

BACKGROUND & AIMS: Vitamin D's pleiotropic effects include immune modulation, and its supplementation has been shown to prevent respiratory tract infections. The effectivity of vitamin D as a therapeutic intervention in critical illness remains less defined. The current study analyzed clinical and immunologic effects of vitamin D levels in patients suffering from coronavirus disease 2019 (COVID-19) induced acute respiratory distress syndrome (ARDS). METHODS: This was a single-center retrospective study in patients receiving intensive care with a confirmed SARS-CoV-2 infection and COVID-19 ARDS. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum levels, pro- and anti-inflammatory cytokines and immune cell subsets were measured on admission as well as after 10-15 days. Clinical parameters were extracted from the patient data management system. Standard operating procedures included the daily administration of vitamin D3 via enteral feeding. RESULTS: A total of 39 patients with COVID-19 ARDS were eligible, of which 26 were included in this study as data on vitamin D status was available. 96% suffered from severe COVID-19 ARDS. All patients without prior vitamin D supplementation (n = 22) had deficient serum levels of 25-hydroxyvitamin D. Vitamin D supplementation resulted in higher serum levels of 25-hydroxyvitamin D but not did not increase 1,25-dihydroxyvitamin D levels after 10-15 days. Clinical parameters did not differ between patients with sufficient or deficient levels of 25-hydroxyvitamin D. Only circulating plasmablasts were higher in patients with 25-hydroxyvitamin D levels ≥30 ng/ml (p = 0.029). Patients with 1,25-dihydroxyvitamin D levels below 20 pg/ml required longer mechanical ventilation (p = 0.045) and had a worse acute physiology and chronic health evaluation (APACHE) II score (p = 0.048). CONCLUSION: The vast majority of COVID-19 ARDS patients had vitamin D deficiency. 25-hydroxyvitamin D status was not related to changes in clinical course, whereas low levels of 1,25-dihydroxyvitamin D were associated with prolonged mechanical ventilation and a worse APACHE II score.

Clinical Significance of Micronutrient Supplementation in Critically Ill COVID-19 Patients with Severe ARDS.

The interplay between inflammation and oxidative stress is a vicious circle, potentially resulting in organ damage. Essential micronutrients such as selenium (Se) and zinc (Zn) support anti-oxidative defense systems and are commonly depleted in severe disease. This single-center retrospective study investigated micronutrient levels under Se and Zn supplementation in critically ill patients with COVID-19 induced acute respiratory distress syndrome (ARDS) and explored potential relationships with immunological and clinical parameters. According to intensive care unit (ICU) standard operating procedures, patients received 1.0 mg of intravenous Se daily on top of artificial nutrition, which contained various amounts of Se and Zn. Micronutrients, inflammatory cytokines, lymphocyte subsets and clinical data were extracted from the patient data management system on admission and after 10 to 14 days of treatment. Forty-six patients were screened for eligibility and 22 patients were included in the study. Twenty-one patients (95%) suffered from severe ARDS and 14 patients (64%) survived to ICU discharge. On admission, the majority of patients had low Se status biomarkers and Zn levels, along with elevated inflammatory parameters. Se supplementation significantly elevated Se (p = 0.027) and selenoprotein P levels (SELENOP; p = 0.016) to normal range. Accordingly, glutathione peroxidase 3 (GPx3) activity increased over time (p = 0.021). Se biomarkers, most notably SELENOP, were inversely correlated with CRP (rs = -0.495), PCT (rs = -0.413), IL-6 (rs = -0.429), IL-1ß (rs = -0.440) and IL-10 (rs = -0.461). Positive associations were found for CD8+ T cells (rs = 0.636), NK cells (rs = 0.772), total IgG (rs = 0.493) and PaO2/FiO2 ratios (rs = 0.504). In addition, survivors tended to have higher Se levels after 10 to 14 days compared to non-survivors (p = 0.075). Sufficient Se and Zn levels may potentially be of clinical significance for an adequate immune response in critically ill patients with severe COVID-19 ARDS.

Current concepts in the evaluation and management of preoperative anemia.

PURPOSE OF REVIEW: In the past years, patient blood management (PBM) has evolved to improve patient's care and safety. Anemia is one of the most common medical diseases in the world and is an independent risk factor for morbidity and mortality. Iron deficiency is the main cause for anemia and constitutes a potentially preventable condition with a great impact on surgical outcome. However, preoperative anemia management is not yet established in most hospitals. Changing workflows and re-thinking is challenging. Numerous published studies confirmed the positive effect of preoperative anemia diagnosis and treatment recently. RECENT FINDINGS: Iron supplementation in iron-deficient anemic (IDA) patients reduce the need for allogenic blood transfusion thereby improving perioperative outcome. SUMMARY: Since the introduction of PBM programs, important movements towards early detection and therapy of preoperative anemia have been observed. However, preoperative anemia management is not implemented on a large scale as many healthcare professionals are not aware of the most recent findings in the field. Preoperative anemia management, particularly iron supplementation in IDA patients, has proven to be highly effective and has a tremendous effect on patient safety and outcome.

Vitamin D supplementation for the treatment of COVID-19: a living systematic review.

BACKGROUND: The role of vitamin D supplementation as a treatment for COVID-19 has been a subject of considerable discussion. A thorough understanding of the current evidence regarding the effectiveness and safety of vitamin D supplementation for COVID-19 based on randomised controlled trials is required. OBJECTIVES: To assess whether vitamin D supplementation is effective and safe for the treatment of COVID-19 in comparison to an active comparator, placebo, or standard of care alone, and to maintain the currency of the evidence, using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register, Web of Science and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies without language restrictions to 11 March 2021. SELECTION CRITERIA: We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating vitamin D supplementation for people with COVID-19, irrespective of disease severity, age, gender or ethnicity. We excluded studies investigating preventive effects, or studies including populations with other coronavirus diseases (severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS)). DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (ROB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the following prioritised outcome categories: individuals with moderate or severe COVID-19: all-cause mortality, clinical status, quality of life, adverse events, serious adverse events, and for individuals with asymptomatic or mild disease: all-cause mortality, development of severe clinical COVID-19 symptoms, quality of life, adverse events, serious adverse events. MAIN RESULTS: We identified three RCTs with 356 participants, of whom 183 received vitamin D. In accordance with the World Health Organization (WHO) clinical progression scale, two studies investigated participants with moderate or severe disease, and one study individuals with mild or asymptomatic disease. The control groups consisted of placebo treatment or standard of care alone. Effectiveness of vitamin D supplementation for people with COVID-19 and moderate to severe disease We included two studies with 313 participants. Due to substantial clinical and methodological diversity of both studies, we were not able to pool data. Vitamin D status was unknown in one study, whereas the other study reported data for vitamin D deficient participants. One study administered multiple doses of oral calcifediol at days 1, 3 and 7,  whereas the other study gave a single high dose of oral cholecalciferol at baseline. We assessed one study with low risk of bias for effectiveness outcomes, and the other with some concerns about randomisation and selective reporting. All-cause mortality at hospital discharge (313 participants) We found two studies reporting data for this outcome. One study reported no deaths when treated with vitamin D out of 50 participants, compared to two deaths out of 26 participants in the control group (Risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.13). The other study reported nine deaths out of 119 individuals in the vitamin D group, whereas six participants out of 118 died in the placebo group (RR 1.49, 95% CI 0.55 to 4.04]. We are very uncertain whether vitamin D has an effect on all-cause mortality at hospital discharge (very low-certainty evidence). Clinical status assessed by the need for invasive mechanical ventilation (237 participants) We found one study reporting data for this outcome. Nine out of 119 participants needed invasive mechanical ventilation when treated with vitamin D, compared to 17 out of 118 participants in the placebo group (RR 0.52, 95% CI 0.24 to 1.13). Vitamin D supplementation may decrease need for invasive mechanical ventilation, but the evidence is uncertain (low-certainty evidence). Quality of life We did not find data for quality of life. Safety of vitamin D supplementation for people with COVID-19 and moderate to severe disease We did not include data from one study, because assessment of serious adverse events was not described and we are concerned that data might have been inconsistently measured. This study reported vomiting in one out of 119 participants immediately after vitamin D intake (RR 2.98, 95% CI 0.12 to 72.30). We are very uncertain whether vitamin D supplementation is associated with higher risk for adverse events (very low-certainty). Effectiveness and safety of vitamin D supplementation for people with COVID-19 and asymptomatic or mild disease We found one study including 40 individuals, which did not report our prioritised outcomes, but instead data for viral clearance, inflammatory markers, and vitamin D serum levels. The authors reported no events of hypercalcaemia, but recording and assessment of further adverse events remains unclear. Authors administered oral cholecalciferol in daily doses for at least 14 days, and continued with weekly doses if vitamin D blood levels were > 50 ng/mL. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the benefits and harms of vitamin D supplementation as a treatment of COVID-19. The evidence for the effectiveness of vitamin D supplementation for the treatment of COVID-19 is very uncertain. Moreover, we found only limited safety information, and were concerned about consistency in measurement and recording of these outcomes. There was substantial clinical and methodological heterogeneity of included studies, mainly because of different supplementation strategies, formulations, vitamin D status of participants, and reported outcomes. There is an urgent need for well-designed and adequately powered randomised controlled trials (RCTs) with an appropriate randomisation procedure, comparability of study arms and preferably double-blinding. We identified 21 ongoing and three completed studies without published results, which indicates that these needs will be addressed and that our findings are subject to change in the future. Due to the living approach of this work, we will update the review periodically.

Effectiveness of Iron Supplementation With or Without Erythropoiesis-Stimulating Agents on Red Blood Cell Utilization in Patients With Preoperative Anaemia Undergoing Elective Surgery: A Systematic Review and Meta-Analysis.

Patient Blood Management (PBM) is an evidence-based, multidisciplinary, patient-centred approach to optimizing the care of patients who might need a blood transfusion. This systematic review aimed to collect the best available evidence on the effectiveness of preoperative iron supplementation with or without erythropoiesis-stimulating agents (ESAs) on red blood cell (RBC) utilization in all-cause anaemic patients scheduled for elective surgery. Five databases and two trial registries were screened. Primary outcomes were the number of patients and the number of RBC units transfused. Effect estimates were synthesized by conducting meta-analyses. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used to assess the certainty of evidence. We identified 29 randomized controlled trials (RCTs) and 2 non-RCTs comparing the effectiveness of preoperative iron monotherapy, or iron + ESAs, to control (no treatment, usual care, placebo). We found that: (1) IV and/or oral iron monotherapy may not result in a reduced number of units transfused and IV iron may not reduce the number of patients transfused (low-certainty evidence); (2) uncertainty exists whether the administration route of iron therapy (IV vs oral) differentially affects RBC utilization (very low-certainty evidence); (3) IV ferric carboxymaltose monotherapy may not result in a different number of patients transfused compared to IV iron sucrose monotherapy (low-certainty evidence); (4) oral iron + ESAs probably results in a reduced number of patients transfused and number of units transfused (moderate-certainty evidence); (5) IV iron + ESAs may result in a reduced number of patients transfused (low-certainty evidence); (6) oral and/or IV iron + ESAs probably results in a reduced number of RBC units transfused in transfused patients (moderate-certainty evidence); (7) uncertainty exists about the effect of oral and/or IV iron + ESAs on the number of patients requiring transfusion of multiple units (very low-certainty evidence). Effect estimates of different haematological parameters and length of stay were synthesized as secondary outcomes. In conclusion, in patients with anaemia of any cause scheduled for elective surgery, the preoperative administration of iron monotherapy may not result in a reduced number of patients or units transfused (low-certainty evidence). Iron supplementation in addition to ESAs probably results in a reduced RBC utilization (moderate-certainty evidence).