Role of preoperative erythropoietin in the optimization of preoperative anemia among surgical patients — A systematic review and meta-analysis

Abstract Preoperative anemia is a common finding. Preoperative allogeneic transfusion, iron therapy, vitamin supplementation and erythropoietin therapy are the current management strategies for preoperative anemia. Previous reviews regarding erythropoietin were limited to specialties, provided little evidence regarding the benefits and risks of erythropoietin in managing preoperative anemia and included non-anemic patients. The purpose of our systematic review was to determine the role of erythropoietin solely in preoperatively anemic patients and to investigate the complications of this treatment modality to produce a guideline for preoperative management of anemic patients for all surgical specialties. The PubMed/Medline, Google Scholar, and Cochrane Library were searched for randomized trials evaluating the efficacy of erythropoietin in preoperative anemia. The risk ratio (RR) and standardized mean difference (SMD) was used to pool the estimates of categorical and continuous outcomes, respectively. Allogeneic transfusion and complications and the 90-day mortality were the primary outcomes, while the postoperative change in hemoglobin, bleeding in milliliters and the number of red blood cell (RBC) packs transfused were the secondary outcomes. Results: Eight studies were included, comprising 734 and 716 patients in the erythropoietin group and non-erythropoietin group, respectively. The pooled estimate by RR for allogeneic transfusion was 0.829 (p = 0.049), while complications and the 90-day mortality were among the 1,318 (p = 0.18) patients. Conclusion: Preoperative erythropoietin provides better outcomes, considering the optimization of preoperative anemia for elective surgical procedures. The benefits of erythropoietin are significantly higher, compared to the control group, while the risks remain equivocal in both groups. We recommend preoperative erythropoietin in anemic patients.

Iron distribution in different tissues of homozygous Mask (msk/msk) mice and the effects of oral iron treatments.

Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary iron absorption, leading to a form of anemia resistant to oral iron supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared to asymptomatic heterozygous (msk/wt) mice, assessing the major parameters of iron status in different organs, at different ages in both sexes. The effect of carbonyl iron diet was analyzed as control iron supplementation being used for many studies in mice. It resulted effective in both anemic control and msk/msk mice, as expected, even if there is no information about its mechanism of absorption. Then, we mainly compared two forms of oral iron supplement, largely used for humans: ferrous sulfate and Sucrosomial iron. In anemic control mice, the two oral formulations corrected hemoglobin levels from 11.40 ± 0.60 to 15.38 ± 1.71 g/dl in 2-4 weeks. Interestingly, in msk/msk mice, ferrous sulfate did not increase hemoglobin likely due to ferroportin/hepcidin-dependent absorption, whereas Sucrosomial iron increased it from 11.50 ± 0.60 to 13.53 ± 0.64 g/dl mainly in the first week followed by a minor increase at 4 weeks with a stable level of 13.30 ± 0.80 g/dl, probably because of alternative absorption. Thus, Sucrosomial iron, already used in other conditions of iron deficiency, may represent a promising option for oral iron supplementation in IRIDA patients.

Flipside of the Coin: Iron Deficiency and Colorectal Cancer.

Iron deficiency, with or without anemia, is the most frequent hematological manifestation in individuals with cancer, and is especially common in patients with colorectal cancer. Iron is a vital micronutrient that plays an essential role in many biological functions, in the context of which it has been found to be intimately linked to cancer biology. To date, however, whereas a large number of studies have comprehensively investigated and reviewed the effects of excess iron on cancer initiation and progression, potential interrelations of iron deficiency with cancer have been largely neglected and are not well-defined. Emerging evidence indicates that reduced iron intake and low systemic iron levels are associated with the pathogenesis of colorectal cancer, suggesting that optimal iron intake must be carefully balanced to avoid both iron deficiency and iron excess. Since iron is vital in the maintenance of immunological functions, insufficient iron availability may enhance oncogenicity by impairing immunosurveillance for neoplastic changes and potentially altering the tumor immune microenvironment. Data from clinical studies support these concepts, showing that iron deficiency is associated with inferior outcomes and reduced response to therapy in patients with colorectal cancer. Here, we elucidate cancer-related effects of iron deficiency, examine preclinical and clinical evidence of its role in tumorigenesis, cancer progression and treatment response. and highlight the importance of adequate iron supplementation to limit these outcomes.

[Moderate anaemia refractory to oral iron in a pregnant woman with a history of bariatric surgery]. / Anemia moderada refractaria al hierro oral en una gestante con antecedente de cirugía bariátrica.

INTRODUCTION: Introduction: bariatric surgery involves nutritional and trace element deficiencies that may have a negative impact if not treated properly, especially in situations such as pregnancy. Case report: a patient who underwent biliopancreatic diversion surgery without subsequent therapeutic adherence consults due to edema; findings included 29-week gestation (type 1 intrauterine growth restriction) and moderate anemia. Vitamin supplementation, oligoelements, enteral nutrition, and intravenous iron were restarted. Due to poor hemoglobin response with repleted iron deposits, recombinant human erythropoietin was associated. Discussion: the most frequent nutritional deficiencies after malabsorptive bariatric surgery are sideropenia and hypoproteinemia. Sideropenia and anemia increase the risk of preterm delivery, low weight, and perinatal mortality. In patients with inadequate response to intravenous iron, treatment with recombinant human erythropoietin may be considered, although its use in pregnant women without chronic renal failure has no indication in the prescribing information of this drug.

INTRODUCCIÓN: Introducción: la cirugía bariátrica (CB) implica déficits nutricionales y de oligoelementos que pueden tener una repercusión negativa en caso de no tratarse adecuadamente, especialmente en situaciones como la gestación. Caso clínico: paciente sometida a CB del tipo de la derivación biliopancreática, sin adherencia terapéutica posterior, que acude por edemas, confirmándose la presencia de una gestación de 29 semanas (feto CIR de tipo I) y de anemia moderada. Se reinició la suplementación de vitaminas, oligoelementos, nutrición enteral y hierro intravenoso (FEIV). Debido a la escasa respuesta de la hemoglobina con depósitos de hierro repletados, se asoció eritropoyetina humana recombinante (rHuEPO). Discusión: los déficits nutricionales más frecuentes tras una CB malabsortiva son la ferropenia y la hipoproteinemia. La ferropenia y la anemia incrementan el riesgo del parto pretérmino, el bajo peso y la mortalidad perinatal. En las pacientes sin adecuada respuesta al FEIV puede plantearse el tratamiento con rHuEPO, aunque su uso en gestantes sin insuficiencia renal crónica no dispone de indicación en la ficha técnica.

Factors influencing safety and efficacy of intravenous iron-carbohydrate nanomedicines: From production to clinical practice.

Iron deficiency is an important subclinical disease affecting over one billion people worldwide. A growing body of clinical records supports the use of intravenous iron-carbohydrate complexes for patients where iron replenishment is necessary and oral iron supplements are either ineffective or cannot be tolerated by the gastrointestinal tract. A critical characteristic of iron-carbohydrate drugs is the complexity of their core-shell structure, which has led to differences in the efficacy and safety of various iron formulations. This review describes parameters influencing the safety and effectiveness of iron-carbohydrate complexes during production, storage, handling, and clinical application. We summarized the physicochemical and biological assessments of commercially available iron carbohydrate nanomedicines to provide an overview of publicly available data. Further, we reviewed studies that described how subtle differences in the manufacturing process of iron-carbohydrate complexes can impact on the physicochemical, biological, and clinical outcomes of original product versus their intended copies or so-called iron "similar" products.

Association Between Anemia and Dementia: A Nationwide, Populationbased Cohort Study in Taiwan.

BACKGROUND: In addition to the traditional risk predictors, whether anemia is an early biomarker of dementia, needs to be confirmed. OBJECTIVE: This population-based cohort study aimed to investigate the dementia risk in patients with newly diagnosed anemia using data from the Taiwan National Health Insurance Research Database. METHODS: All newly diagnosed anemia patients (n = 26,343) with no history of stroke hospitalization, central nervous disease other than dementia, psychiatric disorders, traumatic brain injury, major operations, or blood loss diseases, were enrolled. A group of non-anemic controls, 1:4 matched with anemic patients on the basis of demographics and comorbidities, was also included. A competing risk analysis was used to evaluate the dementia risk in anemic patients compared to that of their matched controls. RESULTS: The adjusted subdistribution hazard ratio (SHR) of dementia risk in anemic patients was 1.14 (95% confidence interval [CI]: 1.08~1.21, p<0.001). Patients with iron supplements tended to exhibit a lower dementia risk (adjusted SHR: 0.84; 95% CI: 0.75~0.94, p=0.002) compared to patients without iron supplement. A subgroup analysis showed that a positive association between dementia and anemia existed in females, those aged 70 years and older, and patients without hypertension, diabetes, or hyperlipidemia. CONCLUSION: The present population-based cohort study identified that newly diagnosed anemia is a risk factor for dementia and also that iron supplementation was able to reduce the risk of dementia in people with iron deficiency anemia.

Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment.

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Effects of anti-TNF-alpha therapy on hemoglobin levels and anemia in patients with inflammatory bowel disease.

BACKGROUND: Tumor necrosis factor-α (TNF-α) is involved in inducing inflammatory anemia. The potential effect of anti-TNF-α agents on anemia in inflammatory bowel diseases (IBD) is still unknown. METHODS: Analytical data and disease characteristics from 362 IBD patients [271 CD/91UC) treated with anti-TNF-α drugs were retrospectively collected. Effects on disease activity, blood markers and prevalence of anemia were assessed after 6 and 12 months of therapy. RESULTS: 29.3% patients presented anemia at baseline, and significantly reduced to 14.4% and 7.8% after 6 and 12 months of therapy, respectively. Mean ±â€¯SD Hb levels increased significantly at month 6, and this increase was sustained at 12 months. Serum markers of iron metabolism increased significantly compared to baseline, as disease activity measured by C-reactive protein (CRP) was reduced. All these effects were observed independently for CD and UC, and were independent of iron supplementation during treatment. Anemia at baseline (OR 4.09; 95%CI 1.98-8.45) and elevated CRP (OR 3.45; 95CI 1.29-9.22) were independently associated with risk of persistent anemia, as well as iron replacement during therapy (OR 4.36; 95%CI 2.07-9.16). CONCLUSIONS: Controlling disease activity with anti-TNF- α therapy significantly and independently associated with resolution of anemia in IBD, with no relevant role for iron replacement therapy.

Reticulocyte Hemoglobin Content (Ret He): A Simple Tool for Evaluation of Iron Status in Childhood Cancer.

BACKGROUND: Cancer-related anemia is a common complication of cancer and its treatment that may be mediated by nutritional deficiency or inflammatory cytokines inhibiting erythropoiesis. AIM: We evaluated the value of reticulocyte hemoglobin content (Ret He) as a marker of iron availability for erythropoiesis in childhood cancer and the impact of oral iron supplementation on hematologic parameters in patients with low Ret He. MATERIALS AND METHODS: This prospective study included 100 pediatric patients with cancer on chemotherapy who were screened for the presence of anemia. Patients with anemia underwent testing for complete blood count including Ret He on Sysmex XE 2100 and assessment of reticulocyte count, serum iron, serum ferritin, transferrin saturation, total iron-binding capacity, and C-reactive protein. Patients were classified according to their level of Ret He into normal or low Ret He using a cutoff level of 28 pg. Patients with low Ret He were subjected to 6 weeks' treatment with oral ion and were followed up with complete blood count and iron profile. RESULTS: Thirty-one (77.5%) patients had normal Ret He, and 9 (22.5%) had low Ret He. Ret He was positively correlated with red cell indices, but not with iron parameters. After oral iron supplementation, a significant increase in hemoglobin, reticulocyte count, and iron was found. CONCLUSIONS: We suggest that Ret He could be used as an easy and affordable tool for the assessment of iron deficiency anemia in childhood cancer during chemotherapy treatment. A trial of oral iron in patients with low Ret He may be useful to correct the associated anemia.

Total Knee Arthroplasty Is Safe in Jehovah's Witness Patients-A 12-Year Perspective.

Despite the evolution of blood management protocols, total knee arthroplasty (TKA) occasionally requires allogeneic blood transfusion. This poses a particular challenge for Jehovah's Witnesses (JW) who believe that the Bible strictly prohibits the use of blood products. The aim of this study was to compare JW and a matched-control cohort of non-JW candidates undergoing TKA to assess the safety using modern blood management protocols. Fifty-five JW patients (63 knees) who underwent TKA at our institution between 2005 and 2017 were matched to 63 non-JW patients (63 knees). Patient demographics, intraoperative details, and postoperative complications including in-hospital complications, revisions, and 90-day readmissions were collected and compared between the groups. Additionally, subgroup analysis was performed comparing JW patients who were administered tranexamic acid (TXA) between the two groups. Baseline demographics did not vary significantly between the study cohorts. The mean follow-up was 3.1 years in both the JW and non-JW cohorts. Postoperative complications, including in-hospital complications (7.9 vs. 4.8%; p = 0.47), revision TKA (1.6 vs. 1.6%; p = 1.00), and 90-day readmission (1.6 vs. 4.8%; p = 0.31) were not significantly different between the JW and non-JW groups. Subgroup analysis demonstrated JW patients who received TXA had a significantly lower decline in postoperative hemoglobin (Hgb) (8.6 vs. 14.0%; p < 0.01). At a follow-up of up to 12 years, JW patients who underwent TKA have outcomes equivalent to non-JW patients without the need for transfusion. Our findings support that surgeons are more likely to optimize JW patients preoperatively with iron and folate supplementation. Despite these variations in preoperative optimization efforts, no significant difference with regard to Hgb or hematocrit levels was demonstrated. Level of evidence is III, retrospective observational study.

Comparison of Therapeutic Efficacy of Ferrous Ascorbate and Iron Polymaltose Complex in Iron Deficiency Anemia in Children: A Randomized Controlled Trial.

OBJECTIVE: To compare the therapeutic efficacy of Ferrous ascorbate (FA) and Iron polymaltose complex (IPC) in Iron deficiency anemia (IDA) in children. METHODS: A randomized controlled trial (RCT) was conducted at a tertiary care hospital with 125 (1-12 y) children having clinical symptoms and signs of IDA. Participants were randomized into FA group and IPC group. Both the groups received iron salts (FA or IPC) randomly in a dose of 6 mg/kg elemental iron for 3 mo and followed up on day 3, day 7, at the end of 1 mo and 3 mo for Hemoglobin (Hb), Mean corpuscular volume (MCV), Red cell distribution width (RDW) and reticulocyte count. RESULTS: Both groups had an improvement in hematological parameters at 3 mo of intervention. The difference in the rise of Hb (g%) at the end of 1 mo in FA group (3.13 ± 1.01) vs. IPC group (2.0 ± 0.85); p = 0.017 and at 3 mo in FA group (4.88 ± 1.28) vs. IPC group (3.33 ± 1.33); p = 0.001 was statistically significant. The difference in the rise of mean Hb was significantly better in FA than the IPC group F [3392] =1.79; p = 0.00 (ANOVA). The difference in the mean increase in MCV (fL) at day 7 in FA group (6.71 ± 8.32) vs. IPC group (2.91 ± 6.16); p = 0.011 and at 1 mo FA group (9.80 ± 8.56) vs. IPC group (5.35 ± 6.11); p = 0.004 was statistically significant. The mean decrease in RDW (%) at 1 mo in FA group (4.23 ± 3.27) vs. IPC group (2.67 ± 1.95); p = 0.005 and at 3 mo in FA group (5.74 ± 3.63) vs. IPC group (4.04 ± 2.17); p = 0.006 was statistically significant. The difference in the rise in mean reticulocyte count at day 3 in FA group (0.88 ± 0.50) vs. IPC group (0.43 ± 1.20); p = 0.017 and at day 7 in FA group (4.00 ± 1.69) vs. IPC group (2.19 ± 1.24); p = 0.001 was statistically significant. F [2294] = 29.2, p = 0.00 (ANOVA). During the study period, the FA group had minor adverse reactions whereas the IPC group had none. CONCLUSIONS: Both the iron salts (FA and IPC) used in the treatment of IDA showed statistically significant improvement in the hematological parameters during the 3 mo of intervention. The improvement in hematological parameters was better in FA supplemented patients as compared to IPC.

The effect of donation activity dwarfs the effect of lifestyle, diet and targeted iron supplementation on blood donor iron stores.

The iron status of blood donors is a subject of concern for blood establishments. The Finnish Red Cross Blood Service addresses iron loss in blood donors by proposing systematic iron supplementation for demographic at-risk donor groups. We measured blood count, ferritin and soluble transferrin receptor (sTfR) and acquired lifestyle and health information from 2200 blood donors of the FinDonor 10000 cohort. We used modern data analysis methods to estimate iron status and factors affecting it with a special focus on the effects of the blood service's iron supplementation policy. Low ferritin (< 15 µg/L), an indicator of low iron stores, was present in 20.6% of pre-menopausal women, 10.6% of post-menopausal women and 6% of men. Anemia co-occurred with iron deficiency more frequently in pre-menopausal women (21 out of 25 cases) than in men (3/6) or post-menopausal women (1/2). In multivariable regression analyses, lifestyle, dietary, and blood donation factors explained up to 38% of the variance in ferritin levels but only ~10% of the variance in sTfR levels. Days since previous donation were positively associated with ferritin levels in all groups while the number of donations during the past 2 years was negatively associated with ferritin levels in pre-menopausal women and men. FRCBS-provided iron supplementation was negatively associated with ferritin levels in men only. Relative importance analyses showed that donation activity accounted for most of the explained variance in ferritin levels while iron supplementation explained less than 1%. Variation in ferritin levels was not significantly associated with variation in self-reported health. Donation activity was the most important factor affecting blood donor iron levels, far ahead of e.g. red-meat consumption or iron supplementation. Importantly, self-reported health of donors with lower iron stores was not lower than self-reported health of donors with higher iron stores.

A case of dystonia with polycythemia and hypermanganesemia caused by SLC30A10 mutation: a treatable inborn error of manganese metabolism.

BACKGROUND: Manganese is a critical trace element that not only has antioxidant properties, but also is essential for various metabolic pathways and neurotransmitters production. However, it can be toxic at high levels, particularly in the central nervous system. Manganese intoxication can be acquired, but an inherited form due to autosomal-recessive mutations in the SLC30A10 gene encoding a Mn transporter protein has also been reported recently. These mutations are associated with significant failure of manganese excretion and its storage in the liver, brain (especially basal ganglia), and other peripheral tissues, resulting in toxicity. CASE PRESENTATION: A 10-year-old boy from consanguineous parents presented with a history of progressive truncal instability, gait difficulty, and frequent falls for 2 months. He had dystonia, rigidity, ataxia, dysarthria, bradykinesia and a plethoric skin. Investigations showed polycythemia, low serum iron and ferritin levels, and increased total iron binding capacity. A brain MRI revealed symmetric hyperintensities in the basal ganglia and dentate nucleuses on TI images that were suggestive of brain metal deposition together with clinical manifestations. Serum calcium and copper levels were normal, while the manganese level was significantly higher than normal values. There was no history of environmental overexposure to manganese. Genetic testing showed a homozygous missense mutation in SLC30A10 (c.C1006T, p.His336Tyr) and Sanger sequencing confirmed a homozygous state in the proband and a heterozygous state in the parents. Regular treatment with monthly infusions of disodium calcium edetate and oral iron compounds resulted in decreased serum manganese and hemoglobin levels to normal values, significant resolution of MRI lesions, and partial improvement of neurological symptoms during 6 months of follow-up. CONCLUSION: The syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by SLC30A10 mutation is a treatable inherited metal deposition syndrome. The patient may only have pure neurological without hepatic manifestations. Although this is a rare and potentially fatal inborn error of metabolism, early diagnosis and continuous chelation therapy might improve the symptoms and prevent disease progression.

Tris(8-Hydroxyquinoline)iron induces apoptotic cell death via oxidative stress and by activating death receptor signaling pathway in human head and neck carcinoma cells.

BACKGROUND: 8-Hydroxyquinoline derivatives have highly sensitive fluorescent chemosensors for metal ions, which are associated with anti-oxidant, anti-tumor and anti-HIV-1 properties. Head and neck squamous cell carcinoma (HNSCC) is associated with a high rate of mortality and novel anti-HNSCC drugs must be developed. Therefore, effective chemotherapy agents are required to address this public health issue. HYPOTHESIS/PURPOSE: The aim of this study was to investigate the inhibitory effect of tris(8-hydroxyquinoline)iron (Feq3) on the HNSCC and the underlying mechanism. STUDY DESIGN/METHODS: A novel 8-hydroxyquinoline derivative, Feq3, was synthesized. The cell viabilities were analyzed using MTT reagent. Apoptosis and the cell cycle distributions were determined by flow cytometer. Reverse transcription-polymerase chain reaction (RT-PCR), immunofluorescence, western blot, MitoSOX and CellROX stain assay were used to study the mechanism of Feq3. Feq3 combined with antioxidants NAC (N-acetylcysteine) and BSO (buthionine sulfoximine) measured the cell viability and intracellular ROS. RESULTS: Feq3 induced the death of HNSCC cells and caused them to exhibit the morphological features of apoptosis. Feq3 also induced apoptosis of SCC9 cells by cell cycle arrest during the G2/M phase and the induced arrest of SCC25 cells in the G0/G1 and G2/M phases, which was associated with decreased cyclin B1/cdc2 and cyclin D/cdk4 expressions. Feq3 increases reactive oxygen species (ROS) and reduces glutathione (GSH) levels, and responds to increased p53 and p21 expressions. Feq3 induced apoptosis by mitochondria-mediated Bax and cytochrome c up-expression and down-expression Bcl-2. Feq3 also up-regulated tBid, which interacts with the mitochondrial pathway and tumor necrosis factor-α (TNF-α)/TNF-Rs, FasL/Fas, and TNF-related apoptosis inducing ligand receptors (TRAIL-Rs)/TRAIL-dependent caspases apoptotic signaling pathway in HNSCC cells. However, Feq3 activates Fas but not FasL in SCC25 cells. Feq3 arrests the growth of HNSCC cells and is involved in the mitochondria- and death receptor (DR)-mediated caspases apoptotic pathway. CONCLUSION: This study is the first to suggest that apoptosis mediates the anti-HNSCC of Feq3. Feq3 has potential as a cancer therapeutic agent against HNSCC.

Albumin-functionalized CuFeS2/photosensitizer nanohybrid for single-laser-induced folate receptor-targeted photothermal and photodynamic therapy.

Multimodal therapy is an emerging medical intervention to overcome the current limitation in cancer therapy combining treatment modalities with different mechanisms of action to eradicate tumors. This study demonstrates a targeted multifunctional bovine serum albumin (BSA)-functionalized CuFeS2/chlorin e6 (Ce6) for synergistic photothermal therapy (PTT) and photodynamic therapy (PDT) effects. The CuFeS2 nanocrystals were synthesized through a simple heating-up approach and transferred into an aqueous phase using BSA in an ultrasonic-assisted microemulsion method. The as-prepared CuFeS2@BSA nanoparticles further conjugated with folic acid (FA) followed by attachment of Ce6 to form the Ce6:CuFeS2@BSA-FA nanohybrid with improved solubility and strong near-infrared (NIR) absorbance and fluorescence. It is the first report to fabricate the targeted Ce6:CuFeS2@BSA-FA hybrid and evaluates their synergistic PTT/PDT effect using a single laser. The Ce6:CuFeS2@BSA-FA hybrid showed lower toxicity in vitro (HeLa and HepG2 cells) and in vivo (zebrafish embryos), while they are selectively recognized and internalized by HeLa cells that over-express folate receptors. Compared to each modality applied separately, the combined single-laser-induced PTT and PDT treatment showed the enhanced generation of heat and reactive oxygen species (ROS) with synergistic cancer killing under 671 nm laser irradiation (10 min, 1 W/cm2). As a biocompatible targeted nanoprobe, the multifunctional nanohybrid holds promise in combined PDT/PTT synergistic therapy to achieve better efficacy.

Multifunctional nanoplatform for photoacoustic imaging-guided combined therapy enhanced by CO induced ferroptosis.

A multifunctional CO/thermo/chemotherapy nanoplatform is here reported, which is composed of mesoporous carbon nanoparticles (MCN) as near infrared (NIR)-responsive drug carrier, doxorubicin (DOX) as chemotherapeutic drug and triiron dodecacarbonyl (FeCO) as thermosensitive CO prodrug. The nanoplatform could absorb near-infrared (NIR) light and convert it into ample heat to trigger CO release and could also release DOX in the acidic tumor microenvironment. More importantly, the generated CO molecules successfully increase cancer cell sensitivity to chemotherapeutics by the ferroptosis pathway. Subsequently, under the guidance of photoacoustic imaging, the FeCO-DOX@MCN nanoplatform demonstrates high treatment efficacies in vitro and in vivo by combination of chemotherapy, photothermal therapy and gas therapy. This multifunctional platform with excellent antitumor efficacy has great potential in precision cancer therapy.

Assessment of adherence to iron supplementation among pregnant women in the Yaounde gynaeco-obstetric and paediatric hospital.

INTRODUCTION: Anemia is a global problem affecting 41.8% of pregnant women. Iron deficiency is the leading cause during pregnancy. Its prevalence among Cameroonian pregnant women was estimated at 50.9% in 2004. Few studies have evaluated women's adherence to iron supplementation prescribed during pregnancy. We carried this study in order to evaluate the rate of adherence to iron supplementation and its determinants during pregnancy. METHODS: The study was cross-sectional descriptive, on postpartum women at the Gynaeco-Obstetric and Pediatric Hospital of Yaoundé during three months. Adherence was measured using the 8-item Morisky Medication Adherence Scale (MMAS-8). The total score was classified as low, moderate and high adherence. RESULTS: For a total of 304 recruited women, 16.4% were highly compliant, 27.6% moderately compliant, while 56% were low compliant with iron supplementation during pregnancy. The reasons for non-adherence were side effects (19.7%), forgetting (70.1%) and inaccessibility of iron supplements (20.1%). Up to 85 (or 28%) women found it boring to take medication daily. Women with no side effects were about thrice most likely to adhere to the iron supplementation than those with side effects: OR = 3.73 [2.43-5.71]; P = 0.04. Women aged 25 years and above were more likely to be non-compliant to iron supplementation than those youngers: OR = 0.40 [0.31-0.88]; P = 0.02. CONCLUSION: To improve adherence to antenatal iron supplementation, it is important to increase communication for behavior change and counseling before or during antenatal care. Forgetting being the main reason for non-adherence, women should keep their iron in a place of easy access.

Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).

BACKGROUND: Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease-mineral and bone disorder (CKD-MBD). This is an update of a review first published in 2011. OBJECTIVES: The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end-points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all-cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random-effects meta-analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes. MAIN RESULTS: We included 104 studies involving 13,744 adults. Sixty-nine new studies were added to this 2018 update.Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron-based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)-oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow-up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years.Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty-seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty-one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias.In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium-based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron-based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron-based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain.In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium-based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow-up of up to 36 months, compared to calcium-based binders. Compared with calcium-based binders, lanthanum had uncertain effects with respect to all-cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment-related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head-to-head studies of iron-based binders compared with calcium. The paucity of placebo-controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient-important outcomes compared with placebo.It is uncertain whether the effects of binders on clinically-relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses. AUTHORS' CONCLUSIONS: In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium-based binders and incur less treatment-related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient-important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron-based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron-based binders may lead to diarrhoea.

Sucrosomial Iron Supplementation in Anemic Patients with Celiac Disease Not Tolerating Oral Ferrous Sulfate: A Prospective Study.

Patients with celiac disease (CD) frequently suffer from iron deficiency anemia (IDA) and may benefit from iron supplementation. However, intolerance to iron sulfate and duodenal atrophy could reduce the efficacy of this supplementation. This study evaluated the efficacy of a new sucrosomial iron formulation in patients with CD. Consecutive patients with CD and IDA were divided into two groups: patients with a known intolerance to iron sulfate were treated with sucrosomial iron (30 mg of iron/day), while those receiving iron supplementation for the first time were assigned to iron sulfate (105 mg of iron/day). Forty-three patients were enrolled (38 females, mean age 49 ± 9 years). After a follow-up of 90 days both groups showed an increase in Hb levels compared to baseline (+10.1% and +16.2% for sucrosomial and sulfate groups, respectively), and a significant improvement in all iron parameters, with no statistical difference between the two groups. Patients treated with sucrosomial iron reported a lower severity of abdominal symptoms, such as abdominal and epigastric pain, abdominal bloating, and constipation, and a higher increase in general well-being (+33% vs. +21%) compared to the iron sulfate group. Sucrosomial iron can be effective in providing iron supplementation in difficult-to-treat populations, such as patients with CD, IDA, and known intolerance to iron sulfate.