Elisa Martín-Montañez

Perioperative anemia management in colorectal cancer patients: A pragmatic approach

Anemia, usually due to iron deficiency, is highly prevalent among patients with colorectal cancer. Inflammatory cytokines lead to iron restricted erythropoiesis further decreasing iron availability and impairing iron utilization. Preoperative anemia predicts for decreased survival. Allogeneic blood transfusion is widely used to correct anemia and is associated with poorer surgical outcomes, increased post-operative nosocomial infections, longer hospital stays, increased rates of cancer recurrence and perioperative venous thromboembolism. Infections are more likely to occur in those with low preoperative serum ferritin level compared to those with normal levels. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management, minimizes or eliminates allogeneic blood transfusion. This includes restrictive transfusion policy, thromboprophylaxis and anemia management to improve outcomes. Normalization of preoperative hemoglobin levels is a World Health Organization recommendation. Iron repletion should be routinely ordered when indicated. Oral iron is poorly tolerated with low adherence based on published evidence. Intravenous iron is safe and effective but is frequently avoided due to misinformation and misinterpretation concerning the incidence and clinical nature of minor infusion reactions. Serious adverse events with intravenous iron are extremely rare. Newer formulations allow complete replacement dosing in 15-60 min markedly facilitating care. Erythropoiesis stimulating agents may improve response rates. A multidisciplinary, multimodal, individualized strategy, collectively termed Patient Blood Management used to minimize or eliminate allogeneic blood transfusion is indicated to improve outcomes.

The cost of post-operative shed blood salvage after total knee arthroplasty: an analysis of 1,093 consecutive procedures

BACKGROUND Requirements for allogeneic red cell transfusion after total knee arthroplasty are still high (20-50%), and salvage and reinfusion of unwashed, filtered post-operative shed blood is an established method for reducing transfusion requirements following this operation. We performed a cost analysis to ascertain whether this alternative is likely to be cost-effective. MATERIALS AND METHODS Data from 1,093 consecutive primary total knee arthroplasties, managed with (reinfusion group, n=763) or without reinfusion of unwashed salvaged blood (control group, n=330), were retrospectively reviewed. The costs of low-vacuum drains, shed blood collection canisters (Bellovac ABT, Wellspect HealthCare and ConstaVac CBC II, Stryker), shed blood reinfusion, acquisition and transfusion of allogeneic red cell concentrate, haemoglobin measurements, and prolonged length of hospital stay were used for the blood management cost analysis. RESULTS Patients in the reinfusion group received 152±64 mL of red blood cells from postoperatively salvaged blood, without clinically relevant incidents, and showed a lower allogeneic transfusion rate (24.5% vs. 8.5%, for the control and reinfusion groups, respectively; p =0.001). There were no differences in post-operative infection rates. Patients receiving allogeneic transfusions stayed in hospital longer (+1.9 days [95% CI: 1.2 to 2.6]). As reinfusion of unwashed salvaged blood reduced the allogeneic transfusion rate, both reinfusion systems may provide net savings in different cost scenarios (€ 4.6 to € 106/patient for Bellovac ABT, and € -51.9 to € 49.9/patient for ConstaVac CBCII). DISCUSSION Return of unwashed salvaged blood after total knee arthroplasty seems to save costs in patients with pre-operative haemoglobin between 12 and 15 g/dL. It is not cost-saving in patients with a pre-operative haemoglobin >15 g/dL, whereas in those with a pre-operative haemoglobin <12 g/dL, although cost-saving, its efficacy could be increased by associating some other blood-saving method.

Ferric carboxymaltose for the treatment of iron-deficiency anemia

Introduction : Anemic patients may benefit from the various intravenous iron replacement options available. Ferric carboxymaltose (FCM) is a new iron formulation (150 kDa) that can be given at high doses (20 mg/kg, up to 1000 mg) over a short period (≤ 15 min), without test dosing. Areas covered : This paper reviews studies dealing with the efficacy and safety of FCM for treating anemia in relatively large numbers of patients, in addition to analyzing the differences regarding clinical conditions, iron doses, follow-up, comparators, and hematologic response targets. Expert opinion : Overall, there is substantial evidence that FCM is effective in treating iron-deficiency anemia in many acute and chronic conditions, with a favorable benefit–risk profile. The efficacy of FCM for correcting anemia is similar to that of iron sucrose, and it is superior to oral iron or placebo in replenishing iron stores. Despite higher acquisition costs (as fewer administrations are needed), treatment with FCM (as well as with iron isomaltoside 1000 or ferumoxytol) seems to be cost-effective when compared to iron sucrose, and is more convenient for patients. There are, however, some aspects (such as hypophosphatemia) and important missing information (such as use in children and pregnant women) that need to be addressed for facilitating a widespread use of FCM.

Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study.

BACKGROUND Requirements for allogeneic red cell transfusion after total lower limb arthroplasty are still high (20-50%), and post-operative intravenous iron has been shown to reduce transfusion requirements for this surgery. We performed a cost analysis to ascertain whether this alternative is also likely to be cost-effective. MATERIALS AND METHODS Data from 182 matched-pairs of total lower limb arthroplasty patients, managed with a restrictive transfusion protocol and without (control group) or with post-operative intravenous iron (iron group), were retrospectively reviewed. Acquisition and administration costs of iron (iron sucrose or ferric carboxymaltose) and allogeneic red cell concentrates, haemoglobin measurements, and prolonged stay in hospital were used for blood management cost analysis. RESULTS Patients in the iron group received 600 mg intravenous iron, without clinically relevant incidents, and had a lower allogeneic transfusion rate (11.5% vs 26.4% for the iron and control groups, respectively; p=0.001). The reduction in transfusion rate was more pronounced in anaemic patients (17% vs 40%; p=0.015) than in non-anaemic ones (9.6% vs 21.2%; p=0.011). There were no differences with respect to post-operative infection rate. Patients receiving allogeneic transfusion stayed in hospital longer (+1.9 days [95% CI: 1.2-2.6]). As intravenous iron reduces the allogeneic transfusion rate, both iron formulations were cost-neutral in the different cost scenarios (-25.5 to 62.1 €/patient for iron sucrose, and -51.1 to 64.4 €/patient for ferric carboxymaltose). DISCUSSION In patients presenting with or without pre-operative anaemia, post-operative intravenous iron after total lower limb arthroplasty seems to be safe and is associated with reduced transfusion rates, without incremental costs. For anaemic patients, its efficacy could be increased by associating some other blood-saving method.

Perioperative intravenous iron; an upfront therapy for treating anaemia and reducing transfusion requirements

Perioperative anaemia, with iron deficiency being its leading cause, is a frequent condition among surgical patients, and has been linked to increased postoperative morbidity and mortality, and decreased quality of life. Postoperative anaemia is even more frequent and is mainly caused by perioperative blood loss, aggravated by inflammation-induced blunting of erythropoiesis. Allogenic transfusion is commonly used for treating acute perioperative anaemia, but it also increases the rate of morbidity and mortality in surgical and critically ill patients. Thus, overall concerns about adverse effects of both preoperative anaemia and allogeneic transfusion have prompted the review of transfusion practice and the search for safer and more biologically rational treatment options. In this paper, the role of intravenous iron therapy (mostly with iron sucrose and ferric carboxymaltose), as a safe and efficacious tool for treating anaemia and reducing transfusion requirements in surgical patients, as well as in other medical areas, has been reviewed. From the analysis of published data and despite the lack of high quality evidence in some areas, it seems fair to conclude that perioperative intravenous iron administration, with or without erythropoiesis stimulating agents, is safe, results in lower transfusion requirements and hastens recovery from postoperative anaemia. In addition, some studies have reported decreased rates of postoperative infection and mortality, and shorter length of hospital stay in surgical patients receiving intravenous iron.

Memory deficits in aging and neurological diseases.

Memory is central to our ability to perform daily life activities and correctly function in society. Improvements in public health and medical treatment for a variety of diseases have resulted in longer life spans; however, age-related memory impairments have been significant sources of morbidity. Loss in memory function is not only associated with aging population but is also a feature of neurodegenerative diseases such as Alzheimers disease and other psychiatric and neurological disorders. Here, we focus on current understanding of the impact of normal aging on memory and what is known about its mechanisms, and further review pathological mechanisms behind the cause of dementia in Alzheimers disease. Finally, we discuss schizophrenia and look into abnormalities in circuit function and neurotransmitter systems that contribute to memory impairment in this illness.

Visual perception and memory systems: from cortex to medial temporal lobe

Visual perception and memory are the most important components of vision processing in the brain. It was thought that the perceptual aspect of a visual stimulus occurs in visual cortical areas and that this serves as the substrate for the formation of visual memory in a distinct part of the brain called the medial temporal lobe. However, current evidence indicates that there is no functional separation of areas. Entire visual cortical pathways and connecting medial temporal lobe are important for both perception and visual memory. Though some aspects of this view are debated, evidence from both sides will be explored here. In this review, we will discuss the anatomical and functional architecture of the entire system and the implications of these structures in visual perception and memory.

Utility and cost of low-vacuum reinfusion drains in patients undergoing surgery for subcapital hip fracture repair. A before and after cohort study.

Postoperative blood loss may be a risk factor for allogeneic blood transfusion (ABT) in patients undergoing subcapital hip fracture (SHF) repair. We investigated the utility and costs of using a low‐vacuum reinfusion drain (Bellovac ABT) within a blood management protocol for reducing ABT requirements in consecutive SHF.

IGF-II promotes neuroprotection and neuroplasticity recovery in a long-lasting model of oxidative damage induced by glucocorticoids

Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT). Furthermore, the involvement of the IGF-IIR was also studied to elucidate its role in the neuroprotective actions of IGF-II. We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). Similar results were obtained when mitochondria function was analysed (cytochrome c oxidase activity, mitochondrial membrane potential and subcellular mitochondrial distribution). Furthermore, neuronal impairment and degeneration were also assessed (synaptophysin and PSD-95 expression, presynaptic function and FluoroJade B® stain). IGF-II was also able to recover the long-lasting neuronal cell damage. Finally, the effects of IGF-II were not blocked by an IGF-IR antagonist, suggesting the involvement of IGF-IIR. Altogether these results suggest that, in or model, IGF-II through IGF-IIR is able to revert the oxidative damage induced by CORT. In accordance with the neuroprotective role of the IGF-II/IGF-IIR reported in our study, pharmacotherapy approaches targeting this pathway may be useful for the treatment of diseases associated with cognitive deficits (i.e., neurodegenerative disorders, depression, etc.).

Involvement of IGF-II receptors in the antioxidant and neuroprotective effects of IGF-II on adult cortical neuronal cultures

Insulin-like growth factor-II (IGF-II) is a naturally occurring peptide that exerts known pleiotropic effects ranging from metabolic modulation to cellular development, growth and survival. IGF-II triggers its actions by binding to and activating IGF (IGF-I and IGF-II) receptors. In this study, we assessed the neuroprotective effect of IGF-II on corticosterone-induced oxidative damage in adult cortical neuronal cultures and the role of IGF-II receptors in this effect. We provide evidence that treatment with IGF-II alleviates the glucocorticoid-induced toxicity to neuronal cultures, and this neuroprotective effect occurred due to a decrease in reactive oxygen species (ROS) production and a return of the antioxidant status to normal levels. IGF-II acts via not only the regulation of synthesis and/or activity of antioxidant enzymes, especially manganese superoxide dismutase, but also the restoration of mitochondrial cytochrome c oxidase activity and mitochondrial membrane potential. Although the antioxidant effect of IGF-I receptor activation has been widely reported, the involvement of the IGF-II receptor in these processes has not been clearly defined. The present report is the first evidence describing the involvement of IGF-II receptors in redox homeostasis. IGF-II may therefore contribute to the mechanisms of neuroprotection by acting as an antioxidant, reducing the neurodegeneration induced by oxidative insults. These results open the field to new pharmacological approaches to the treatment of diseases involving imbalanced redox homeostasis. In this study, we demonstrated that the antioxidant effect of IGF-II is at least partially mediated by IGF-II receptors.