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Background: Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors. Methods: We searched MEDLINE, Embase, and Cochrane databases for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with greater than or equal to 48 weeks of follow-up. The primary outcome was major adverse cardiovascular event (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke. Treatment effects were pooled using random-effects models. Results: Twenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD, and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio, 0.99; 95% confidence interval [CI], 0.92 to 1.08) or people with nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (risk ratio, 1.10; 95% CI, 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable with ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections, and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials. Conclusions: There was no evidence of a difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD. (PROSPERO registration number, CRD42021278011.) [ABSTRACT FROM AUTHOR]

Background: Hemodialysis patients are common to have renal anemia in the nephrology practice. For the renal anemia, the high-dose iron from the intravenous route is an important treatment option. We can understand the treatment effects and cardiovascular events of high-dose intravenous iron reviewing the randomized clinical trials. Methods: We compared the high-dose and low-dose iron treatments to find if the high-dose intravenous iron can influence the hematological parameters more significantly than the low-dose iron. The cardiovascular events were also analyzed for the high-dose iron treatment. Six studies with a total of 2422 renal anemia patients under hemodialysis were enrolled. We focused the outcomes of hemoglobin, transferrin saturation percentage, ferritin, erythropoietin dose, and cardiovascular events. Results: The high-dose intravenous iron might be associated with a greater number of ferritin, transferrin saturation percentage, and hemoglobin. In addition, the erythropoietin dose was less needed to maintain the ideal hemoglobin range in the high-dose intravenous iron group. Conclusions: In current meta-analysis, the high-dose intravenous iron might show the superior effects on the ferritin, transferrin saturation percentage, and hemoglobin levels and needed dose of erythropoietin when compared to low-dose iron treatment. [ABSTRACT FROM AUTHOR]

Background & Objective: The aim of the current study was comparison of the effectiveness of intravenous iron sucrose versus oral ferrous fumarate for the treatment of iron deficiency anemia during pregnancy. Materials & Methods: This is a prospective randomized clinical trial enrolling 100 pregnant women with iron deficiency anemia who visited the Al-diwaniya Educational Hospital for maternity and children from October 2022 to July 2023 whose ferritin level was less than 15 ng/ml and Hb level was between 70-10.9g/L. They were treated with either intravenous iron sucrose or oral ferrous fumarate for four weeks. Formerly, patients were allocated into two groups. The patients in the group I received ferrous fumarate pills, each enclosed with elemental Iron 100 mg. Group II got 100 ml of 0.9% NaCl containing a dose of iron sucrose dissolved in it and calculated by a specific equation. After four weeks, serum ferritin and hemoglobin levels were assessed, and the adverse effects were also monitored. Results: Comparing hemoglobin levels produces a substantial pre- and post-treatment difference (P=0.001). Serum Ferritin Level harvest significant differences pre- and posttreatment (P=0.001). The post-treatment comparison of the two groups showed a significant difference in each group (P= 0.001). Conclusion: Maternal iron reserves are more effectively increased by intravenous ferrous sucrose than by oral ferrous fumarate. [ABSTRACT FROM AUTHOR]

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are available online to subscribers. Monographs can be customized to meet the needs of a facility. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, contact Wolters Kluwer customer service at 866-397-3433. [ABSTRACT FROM AUTHOR]

Total hip arthroplasties aim to improve quality of life and reduce pain in patients suffering from late-stage hip osteoarthritis. On the other hand, it may represent a risky surgical procedure in people who refuse blood products because of religious beliefs, such as Jehovah's Witnesses (JW). Preoperative optimisation protocols of these patients allow medical professionals to perform arthroplasties in a safer manner, avoiding allogeneic blood transfusion. In our retrospective study, two groups of patients were evaluated. Group 1 included JW patients who underwent a preoperative Hb optimisation program; Group 2 included non-JW patients authorizing transfusion in case of necessity. Differences in Hb levels were as follows: before surgery (JW 14.24 ± 1.10 vs. non-JW 12.48 ± 1.00, p-value ≤ 0.05), and after surgery (day 1 Hb: JW 12.88 ± 0.90 vs. non-JW 10.04 ± 1.30, p-value ≤ 0.05; day 3 Hb: JW 14.65 ± 0.80 vs. non-JW 9.10 ± 0.90 p-value ≤ 0.05). Moreover, cost-effectiveness strategies were evaluated in both groups. Our findings support that patient blood management programs are a safe and good strategy in hip prosthetic surgery, decreasing risks and transfusion overuse. [ABSTRACT FROM AUTHOR]

Complications of chronic suppurative otitis media (CSOM) are still prevalent in developing countries, with some of the patients presenting with rare complications. CSOM can affect the external auditory canal (EAC) in different ways, and the most common affectation is EAC stenosis or atresia. Manifesting with necrotizing fasciitis of the EAC is extremely rare. Only a few cases have been reported in the literature, and none was from otitis media. In this article, we reported a rare case of necrotizing fasciitis of the EAC from CSOM in a malnourished child. [ABSTRACT FROM AUTHOR]

Peripheral blood hematopoietic progenitor cell harvest by apheresis in pediatric patients, a double-edged sword, has advantages and disadvantages over conventional bone marrow transplantation. The effect of granulocyte colony-stimulating factor (G-CSF) mobilization on hemostasis in literature is very scarce. A 3-year-old female child with metastatic neuroblastoma planned for autologous transplant. Following G-CSF mobilization (75 mg; 4 days), the procedure was performed with all default parameters in Spectra Optia with an acid citrate dextrose (ACD) flow rate 1:12, assuming 3-total blood volume (TBV) to be processed with 150 ml of expected collection with target yield of 6 x 106 CD34 cells/kg. Despite normal coagulation laboratory parameters, it was abandoned for reasons such as low-flow alarms and thrombi in the kit tubings. In the subsequent procedures, the ACD to whole blood ratio was decreased to 1:16, and used bolus of heparin was followed by continuous heparin infusion throughout the procedure. Despite using heparin anticoagulation, a long thrombus was aspirated at needleless port. The procedure was completed with continuous low-flow alarms. A cumulative dose of 5.67 x 106 CD34 cells/kg was achieved over four procedures, but the cause of hypercoagulability was unknown. All the coagulation parameters were within normal limits before and after the procedure. The exact cause for hypercoagulability remains elusive. There are no studies or case reports in the pediatric population on hypercoagulability following apheresis procedure after G-CSF mobilization, but evidence is available for adults, with lack of explanation. It can also be due to low draw flow from the patient side or embolization of thrombi developed in the anticoagulant unprimed site in the kit tubings. More extensive studies are required to explain the mechanism of hypercoagulability during apheresis procedures in the pediatric population. [ABSTRACT FROM AUTHOR]

The article offers information on daprodustat, a hypoxia-inducible factor prolyl hydroxylase (HIF PH) inhibitor and a hematopoietic agent. Its uses include for the treatment of anemia due to chronic kidney disease in adults who have been receiving dialysis for at least four months. Also mentioned are its dosage and administration, drug interactions, and advice to patients.

Purpose To determine the effectiveness of pharmacy consultation in managing epoetin alfa-epbx dosing for inpatients on hemodialysis. Methods This multisite, retrospective cohort study evaluated the implementation of an initial dose consultation for epoetin alfa-epbx by pharmacists. A pre-post cohort study evaluated patients from August 2020 through January 2021 and August 2021 through January 2022, respectively. Hospitalized patients were included if they were at least 18 years of age, received hemodialysis, and were administered an erythropoiesis-stimulating agent (ESA) for anemia due to chronic kidney disease. Patients were excluded for religious objections to receiving blood products or if patients were discharged or died before their first hemodialysis session. The primary outcome was the average epoetin alfa-epbx acquisition cost per patient. Secondary endpoints were the epoetin alfa-epbx overall pharmacy purchasing cost, the average dose, and the number of administered doses. A subgroup analysis was performed for patients in the post group with an outpatient ESA before admission to determine the epoetin alfa-epbx days saved. Results A total of 264 patients were included in the pre group, and 272 patients were included in the post group. The average acquisition cost was significantly lower in the post group ($1,681.77 vs $1,041.35, P < 0.0001). The overall pharmacy purchasing cost was also lower in the post group ($148,970.89 vs $127,873.25). The post group had a significantly lower average dose (13,694 vs 10,112 units, P = 0.0004), while the number of administered doses did not differ significantly between the groups (2.09 vs 1.79 doses, P = 0.0668). The subgroup analysis included 83 patients, which yielded 53 epoetin alfa-epbx days saved. Conclusion Pharmacist-driven ESA dosing was associated with significant decreases in ESA average acquisition cost and average total dose per patient. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to evaluate the long-term clinical efficacy of epoetin alfa and darbepoetin alfa in patients with myelodysplastic syndrome (MDS) in a real-life setting. Materials and Methods: A total of 204 patients with low-risk or intermediate-1-risk MDS who received epoetin alfa or darbepoetin alfa were included. Hemoglobin levels and transfusion needs were recorded before treatment and at 12 months, 24 months, 36 months, and 48 months of treatment. Results: At the 36-month (p=0.025) and 48-month (p=0.022) visits, epoetin alfa yielded significantly higher hemoglobin levels compared to darbepoetin alfa. Transfusion needs were also significantly lower with epoetin alfa compared to darbepoetin alfa at 24 months (p=0.012) and in the low-risk group compared to the intermediate-risk group at 24 months (p=0.018), 36 months (p=0.025), and 48 months (p<0.001). Treatment response rates at the 24-month, 36-month, and 48-month visits in the epoetin alfa (43.0%, 33.6%, and 27.1%), darbepoetin alfa (29.9%, 22.7%, and 16.5%), low-risk (39.3%, 30.0%, and 26.0%), and intermediate-risk (29.6%, 24.1%, and 11.1%) groups were lower than those obtained at 12 months, and the values differed significantly for the 36-month and 48-month visits with values ranging from p<0.05 to p<0.001. Conclusion: This real-life long-term ESA extension study investigated the clinical efficacy of epoetin alfa and darbepoetin alfa for up to 48 months, revealing that treatment efficacy reached a plateau starting from the 24th month of therapy with a continuing decrease in treatment response rates regardless of treatment type, risk status, or gender. Nonetheless, significantly higher hemoglobin levels and marked improvement in transfusion needs were evident in epoetin-treated patients compared to darbepoetin-treated patients and in the low-risk group compared to the intermediate-risk group. [ABSTRACT FROM AUTHOR]

Introduction: The use of erythropoiesis-stimulating agents (ESAs) for treatment of chemotherapy-induced anemia (CIA) has been linked to potential negative health effects. Additionally, research has identified disparities in ESA utilization for CIA treatment. This study examines (1) health disparities in ESA use and (2) whether reimbursement (Medicare National Coverage Determination [NCD]) or regulatory (Risk Evaluation and Mitigation Strategy [REMS]) policies impacted disparities. Methods: In a retrospective cohort study (2006–2018) among 1,747,889 patients with cancer in the United States receiving myelosuppressive chemotherapy at age ≥ 65 years, differences in ESA use for CIA were estimated using generalized estimating equation models, adjusting for policy periods, demographic characteristics, and clinical factors extracted from Medicare claims data. Results: After controlling for covariates, ESA use was higher among Black, female, and urban patients in all policy periods, but these disparities decreased significantly following the NCD. The gap continued to close through the REMS period. Disparities in ESA use across geographic regions were modest, and ESA use disparities across socioeconomic characteristics (area deprivation index or dual Medicare/Medicaid eligibility) were not observed. Conclusions: Being female, Black, or an urban resident was associated with higher ESA use for CIA in older patients with cancer. Both NCD and REMS implementation helped reduce disparities. REMS release was not observed to contribute to racial, sex, and rural–urban disparities in ESA use for CIA. [ABSTRACT FROM AUTHOR]

Aim/Background: Several branded pharmaceuticals and generic medicines are available in the market for the management of End-Stage Renal Disease (ESRD) as a supportive care, and clinicians are unaware of the cost minimization and cost consequences aspects of these medications. Thus, this study aimed to compare the prices of branded versus generic medicines for ESRD treatment and to present the cost savings with a generic alternative. Materials and Methods: A prospective observational study was conducted among ESRD patients from three different tertiary care teaching hospitals in South India. The cost of branded pharmaceuticals were determined using the most recent current index of medical specialties, while the prices of generic medicines were accessed using the Pradhan Mantri Bhartiya Jan Aushadhi Pariyojana scheme, 2022. Results: The data were collected from 385 patients with ESRD. All Jan Aushadhi generic medicines were less expensive when compared to the branded medicines. The cost of ESRD medicines accessible in India varies greatly. The greatest difference in percentage cost savings were noted with amlodipine 5 mg tab (93.03%), voglibose 0.2mg/tab (88.10%), calcium carbonate + Vitamin D3 supplements 500 mg tab (80.27%), torsemide 10 mg tab (78.01%), and hematopoietic agent, erythropoietin 2000 U/inj (75.38%). Conclusion: The haematopoietic medicines and antidiabetic insulin injections were the most expensive medicines among the study population. Our research indicates that replacing the generic medicines with the branded medicines could help in reducing the cost burden. Healthcare professionals may consider prescribing generic medicines for cost-savings. [ABSTRACT FROM AUTHOR]

Background: The Canadian Blood Services Cord Blood Bank (CBS CBB) was created to improve access to stem cell products for transplantation for patients across ethnic groups. An analysis of distributed units is needed to assess the effectiveness of the bank to meet the needs of patients from different ethnic groups. Methods: A descriptive analysis was performed on all cord blood units distributed from the CBS' CBB as of 30 June 2022. Results: Distribution of the first 60 units based on CBS' CBB inventory has been linear over time. A similar proportion of cord blood unit (CBU) recipients were pediatric or adult. More than half of the cord blood units (56.7%) were distributed to recipients outside of Canada, and CBUs were used to treat a broad range of hematologic and immune disorders. 43.3% of distributed CBUs were of non-Caucasian ethnicity and 18% were from donors self-reporting as multi-ethnic. The mean total nucleated cell counts and total CD34+ cell counts were 1.9 ± 0.1 × 109 cells and 5.3 ± 0.5 × 106 CD34+ cells, respectively. CD34+ cells per kg (recipient weight) varied significantly between pediatric (age 0–4), adolescent (age 5–17) and adult recipients (age 18 and older) (3.1 ± 0.5, 1.4 ± 0.5 and 0.9 ± 0.07 × 105 CD34+ cells/kg, respectively). HLA matching was 6/6 (15%), 5/6 (47%) or 4/6 (38%). Conclusions: The CBS' CBB has facilitated the utilization of banked units for patients across a broad range of ages, geographic distribution, ethnicity, and diseases. Distributed units were well matched for HLA alleles and contained robust cell counts, reflecting a high-quality inventory with significant utility. [ABSTRACT FROM AUTHOR]

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Simple Summary: Several novel therapies are being developed to improve the management of patients with myelodysplastic syndromes. They include drugs aimed at improving hematopoiesis and differentiation of myeloid precursors, hypomethylating agents, several compounds that target intracellular molecular pathways, and immunotherapies. In this review article, we discuss how the novel drugs may address the several unmet needs of lower- and higher-risk patients. Myelodysplastic syndromes (MDS) are a very heterogeneous disease, with extremely variable clinical features and outcomes. Current management relies on risk stratification based on IPSS and IPSS-R, which categorizes patients into low (LR-) and high-risk (HR-) MDS. Therapeutic strategies in LR-MDS patients mainly consist of erythropoiesis stimulating agents (ESAs), transfusion support, and luspatercept or lenalidomide for selected patients. Current unmet needs include the limited options available after treatment failure, and the consequent transfusion burden with several hospital admissions and poor quality of life. Therapeutic approaches in HR-MDS patients are aimed at changing the natural course of the disease and hypometylating agents (HMA) are the first choice. The only potentially curative treatment is allogeneic stem cell transplant (allo-HCT), restricted to a minority of young and fit candidates. Patients unfit for or those that relapse after the abovementioned options harbor an adverse prognosis, with limited overall survival and frequent leukemic evolution. Recent advances in genetic mutations and intracellular pathways that are relevant for MDS pathogenesis are improving disease risk stratification and highlighting therapeutic targets addressed by novel agents. Several drugs are under evaluation for LR and HR patients, which differ by their mechanism of action, reported efficacy, and phase of development. This review analyzes the current unmet clinical needs for MDS patients and provides a critical overview of the novel agents under development in this setting. [ABSTRACT FROM AUTHOR]

Background: Iron supplementation improves the erythropoiesis-stimulating agents' (ESAs) response in chemotherapy-related anemia. The primary aim of our study is to assess the efficacy of sucrosomial iron, a new oral iron formulation, in cancer patients with chemotherapy-induced anemia treated with ESAs. The secondary objectives included the efficacy into two subgroups of patients (iron replete and functional iron deficiency) between the two study arms, safety and the effect on transfusion need.Methods: In this randomized, multicentre, open-label, phase III clinical trial, 60 cancer patients were enrolled. Each patient was randomly assigned (1:1) to receive 12 weeks of oral sucrosomial iron at the dose of 30 mg daily in combination with ESAs or no supplementation to ESA treatment. The endpoint considered for efficacy was the proportion of patients achieving complete hematological response at 12 weeks (increase in Hb > 2 g/dL from baseline, without RBC transfusions in the previous 28 days or achieving Hb ≥ 12 g/dL).Results: There was a statistically significant association between oral sucrosomial iron supplementation in combination with ESAs and the achievement of a complete hematological response. This response was achieved within 12 weeks by 31% of patients in the control group and by 52% of patients supplemented with oral sucrosomial iron. A trend of greater response in sucrosomial iron arm was found in both subgroups. No difference was observed about safety and transfusion need.Conclusions: Sucrosomial iron is well tolerated and its combination with ESAs improves the hematological response in cancer patients with chemotherapy-related anemia.Trial Registration Number and Date Of Registration: This study has been reviewed by the Institutional Ethics Committee of the IRCCS Policlinico San Matteo Foundation, Pavia, Italy (28/04/2015; prot. N. 20,150,002,059), and by the Institutional Ethics Committee of the other Italian oncological centers involved in this study. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis is a very common skeletal disorder that increases the risk of fractures. However, the treatment of osteoporosis is challenging. Hypoxia-inducible factor-1α (HIF-1α) plays an important role in bone metabolism. Roxadustat is a novel HIF stabilizer, and its effects on bone metabolism remain unknown. This study aimed to investigate the effects of roxadustat on osteoblast differentiation and bone remodeling in an ovariectomized (OVX) rat model. Methods: In vitro, primary mouse calvarial osteoblasts were treated with roxadustat. Alkaline phosphatase (ALP) activity and extracellular matrix mineralization were assessed. The mRNA and protein expression levels of osteogenic markers were detected. The effects of roxadustat on the HIF-1α and Wnt/β-catenin pathways were evaluated. Furthermore, osteoblast differentiation was assessed again after HIF-1α expression knockdown or inhibition of the Wnt/β-catenin pathway. In vivo, roxadustat was administered orally to OVX rats for 12 weeks. Then, bone histomorphometric analysis was performed. The protein expression levels of the osteogenic markers HIF-1α and β-catenin in bone tissue were detected. Results: In vitro, roxadustat significantly increased ALP staining intensity, enhanced matrix mineralization and upregulated the expression of osteogenic markers at the mRNA and protein levels in osteoblasts compared with the control group. Roxadustat activated the HIF-1α and Wnt/β-catenin pathways. HIF-1α knockdown or Wnt/β-catenin pathway inhibition significantly attenuated roxadustat-promoted osteoblast differentiation. In vivo, roxadustat administration improved bone microarchitecture deterioration and alleviated bone loss in OVX rats by promoting bone formation and inhibiting bone resorption. Roxadustat upregulated the protein expression levels of the osteogenic markers, HIF-1α and β-catenin in the bone tissue of OVX rats. Conclusion: Roxadustat promoted osteoblast differentiation and prevented bone loss in OVX rats. The use of roxadustat may be a new promising strategy to treat osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Preoperative anaemia is a risk factor for adverse postoperative outcomes after cardiac surgery. Iron deficiency is a frequent cause of low preoperative haemoglobin. An effective treatment for preoperative anaemia associated with iron deficiency has not been determined.Methods: We conducted a single-centre, open-label, pragmatic randomised trial, enrolling 156 elective cardiac surgery patients who had low preoperative haemoglobin (100-130 g L-1) with iron deficiency (serum ferritin <100 μg L-1 or transferrin saturation <30%) to compare intravenous ferric derisomaltose 1000 mg and darbepoetin 200 μg subcutaneously (intervention group) with oral ferrous sulphate 600 mg daily (control group). The primary outcome was transfusion of at least one unit of allogeneic red cells during surgery and within the following 5 days. Secondary outcomes included the change in haemoglobin concentration between randomisation and surgery, red cell transfusion volume, postoperative blood loss, pre-specified postoperative complications, length of hospital stay, and in-hospital death.Results: The odds of red cell transfusion were lower in the intervention group compared with the control group (adjusted odds ratio=0.33; 95% confidence interval [CI], 0.15-0.75; P=0.008). Of the secondary outcomes, the only significant difference was the increase in haemoglobin between randomisation and surgery, intervention vs control 9.5 g L-1 (95% CI, 6.8-12.2; P<0.001).Conclusions: In patients with a low preoperative haemoglobin and iron deficiency, preoperative treatment with a single dose of ferric derisomaltose and darbepoetin decreased the proportion of participants who received a perioperative blood transfusion as a consequence of a greater increase in haemoglobin compared with treatment with oral ferrous sulphate.Clinical Trial Registration: ISRCTN Number: 41421863; EUDRACT number: 2011-003695-36. [ABSTRACT FROM AUTHOR]

The article provides information on the drug Efapegrastim-xnst. Efapegrastim-xnst is a leukocyte growth factor classified as a hematopoietic agent under the brand name Rolvedon. It is indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation and to decrease the incidence of infection, as manifested by febrile neutropenia, in adult patients with non-myeloid malignancies. It may cause splenic rupture, leukocytosis and thrombocytopenia.

A 27-year-old female patient who came for branchial cyst excision was found to have cyanosis and a saturation gap during preanesthetic check-up and hence she was referred to haematology for further workup. She had a Hb of 9 gm% with all other baseline tests as normal. Blood samples were sent for methaemoglobin estimation and related work up to the National Institute of Immunohematology (NIIH) Mumbai. She was diagnosed as a case of Methemoglobinemia with a methaemoglobin level of 68.7% with NADH cytochrome B5 reductase activity of 10.82 IU/g Hb. The drug of choice for treatment is Methylene blue and hence G6PD deficiency had to be ruled out prior to initiating therapy. She was found to have a concurrent existence of G6PD deficiency. The blood sample was further sent to NIIH for genetic confirmation. We avoided methylene blue and other precipitating factors that could trigger a haemolysis. She was further consulted by the Patient blood management team to optimize her erythropoiesis and avoid unnecessary transfusions. Anaesthetic consultation and planning were done to avoid drugs that could induce haemolysis. She was started on Vitamin C, Niacin, hematinic and advised to follow up after a month. She was symptomatically better. Cyanosis had reduced, and Hb improved to 12 gm%. She was taken up for surgery with all precautions. The surgery and the post-operative period were uneventful. She was discharged on postoperative day 4 with an advice to continue Vitamin C & Niacin and to follow-up in Haematology OPD after a month. [ABSTRACT FROM AUTHOR]

The role of the sympathetic nervous system (SNS) in hematopoietic stem and progenitor cell (HSPC) mobilization has been largely investigated. However, there is a critical need for the identification of the underlying contributing factors to improve HSPC yield for transplantation. It has been demonstrated that miR-886-3p targets stromal-derived factor-1 (SDF-1), the central mediator of mobilization, and therefore may play a part in this process. Besides, miR-886-3p expression can be epigenetically regulated through DNA methylation modifications inits gene promoter. Here, to assess the contribution of miR-886-3p and other epigenetic factors in HSPC mobilization, human bone marrow-derived mesenchymal stem cells (MSCs) were treated with the β-adrenergic agonist of isoprenaline. The expression of miR-886-3p and SDF-1and the gene promoter methylation status of this miRNA were then respectively evaluated through the appropriate PCR techniques. As expected, despite a transient initial increase in SDF-1mRNA level, its expression reduced, and miR-886-3plevel remarkably increased 48 h following treatment. The gene promoter methylation pattern of miR-886-3p also changed from a full methylated state to a partially methylated one. Together, our findings suggest that miR-886-3p can be epigenetically regulated and through suppressing the expression of SDF-1 play an active role in the SNS-mediated HSPC mobilization. [ABSTRACT FROM AUTHOR]

Diallyl sulphide (DAS), the pungent component of garlic, is known to have several medicinal properties and has recently been shown to have radiomitigative properties. The present study was performed to better understand its mode of action in rendering radiomitigation. Evaluation of the colonogenic ability of hematopoietic progenitor cells (HPCs) on methocult media, proliferation and differentiation of hematopoietic stem cells (HSCs), and transplantation of stem cells were performed. The supporting tissue of HSCs was also evaluated by examining the histology of bone marrow and in vitro colony-forming unit-fibroblast (CFU-F) count. Alterations in the levels of IL-5, IL-6 and COX-2 were studied as a function of radiation or DAS treatment. It was observed that an increase in proliferation and differentiation of hematopoietic stem and progenitor cells occurred by postirradiation DAS administration. It also resulted in increased circulating and bone marrow homing of transplanted stem cells. Enhancement in bone marrow cellularity, CFU-F count, and cytokine IL-5 level were also evident. All those actions of DAS that could possibly add to its radiomitigative potential and can be attributed to its HDAC inhibitory properties, as was observed by the reversal radiation induced increase in histone acetylation. [ABSTRACT FROM AUTHOR]

Background: Among patients with chronic kidney disease (CKD), the use of recombinant human erythropoietin and its derivatives for the treatment of anemia has been linked to a possibly increased risk of stroke, myocardial infarction, and other adverse events. Several trials have suggested that hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors (PHIs) are as effective as erythropoiesis-stimulating agents (ESAs) in increasing hemoglobin levels.Methods: In this randomized, open-label, phase 3 trial, we assigned patients with CKD who were undergoing dialysis and who had a hemoglobin level of 8.0 to 11.5 g per deciliter to receive an oral HIF-PHI (daprodustat) or an injectable ESA (epoetin alfa if they were receiving hemodialysis or darbepoetin alfa if they were receiving peritoneal dialysis). The two primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 (noninferiority margin, -0.75 g per deciliter) and the first occurrence of a major adverse cardiovascular event (a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), with a noninferiority margin of 1.25.Results: A total of 2964 patients underwent randomization. The mean (±SD) baseline hemoglobin level was 10.4±1.0 g per deciliter overall. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.28±0.02 g per deciliter in the daprodustat group and 0.10±0.02 g per deciliter in the ESA group (difference, 0.18 g per deciliter; 95% confidence interval [CI], 0.12 to 0.24), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 2.5 years, a major adverse cardiovascular event occurred in 374 of 1487 patients (25.2%) in the daprodustat group and in 394 of 1477 (26.7%) in the ESA group (hazard ratio, 0.93; 95% CI, 0.81 to 1.07), which also met the prespecified noninferiority margin for daprodustat. The percentages of patients with other adverse events were similar in the two groups.Conclusions: Among patients with CKD undergoing dialysis, daprodustat was noninferior to ESAs regarding the change in the hemoglobin level from baseline and cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-D ClinicalTrials.gov number, NCT02879305.). [ABSTRACT FROM AUTHOR]

Background: Daprodustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor. In patients with chronic kidney disease (CKD) who are not undergoing dialysis, the efficacy and safety of daprodustat, as compared with the conventional erythropoiesis-stimulating agent darbepoetin alfa, are unknown.Methods: In this randomized, open-label, phase 3 trial with blinded adjudication of cardiovascular outcomes, we compared daprodustat with darbepoetin alfa for the treatment of anemia in patients with CKD who were not undergoing dialysis. The primary outcomes were the mean change in the hemoglobin level from baseline to weeks 28 through 52 and the first occurrence of a major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke).Results: Overall, 3872 patients were randomly assigned to receive daprodustat or darbepoetin alfa. The mean (±SD) baseline hemoglobin levels were similar in the two groups. The mean (±SE) change in the hemoglobin level from baseline to weeks 28 through 52 was 0.74±0.02 g per deciliter in the daprodustat group and 0.66±0.02 g per deciliter in the darbepoetin alfa group (difference, 0.08 g per deciliter; 95% confidence interval [CI], 0.03 to 0.13), which met the prespecified noninferiority margin of -0.75 g per deciliter. During a median follow-up of 1.9 years, a first MACE occurred in 378 of 1937 patients (19.5%) in the daprodustat group and in 371 of 1935 patients (19.2%) in the darbepoetin alfa group (hazard ratio, 1.03; 95% CI, 0.89 to 1.19), which met the prespecified noninferiority margin of 1.25. The percentages of patients with adverse events were similar in the two groups.Conclusions: Among patients with CKD and anemia who were not undergoing dialysis, daprodustat was noninferior to darbepoetin alfa with respect to the change in the hemoglobin level from baseline and with respect to cardiovascular outcomes. (Funded by GlaxoSmithKline; ASCEND-ND ClinicalTrials.gov number, NCT02876835.). [ABSTRACT FROM AUTHOR]

Background: The diversity demography of coronavirus disease 2019 (COVID-19) has prompted us to collect data in our workplace. These data are essential because they can serve as a data bank of demographics in one big hospital in East Java. We analyzed patients' characteristics with COVID-19 admitted to the Intensive Care Unit (ICU) Special Hospital for Infections, Airlangga University, Surabaya. Methods: Retrospective study from medical record of 180 patients with confirmed COVID-19 admitted to the ICU Special Hospital for Infections, Airlangga University of Surabaya between April - September 2020. Results: Most of the patients were male (67.2%), with median age was 55 (22-83) years. The body mass index (BMI) data consisted of normal (48.9%), overweight (39.4%), obesity class I 7.8%, obesity class II 1.1%, obesity class III 0.6%, and underweight 2.2%. We found severe acute respiratory distress syndrome (ARDS) in 63.9%. The use of invasive mechanical ventilation was 74% of the total patients. Most of the patients (85%) had comorbidity: hypertension, diabetes mellitus, and geriatrics. The average length of stay in the ICU was 8.5 days. We transferred 29% of patients to a low-care ward, and 66.7% died. We identified gastrointestinal symptoms on admission to the ICU were 43.3%, predominantly by nausea and vomiting. Forty-six point seven percent of patients with gastrointestinal symptoms during hospitalization consisted of gastric retention and diarrhea, some with hematin. Conclusion: The demographic data we present above are limited in our area. The demographic data of COVID-19 patients in other places may be different from the information we obtained. However, data like this may represent the patient's condition in areas similar to ours. Besides, this data can warn that the patient's condition, as in our data, requires special attention. It is necessary to add data from all corners of Indonesia to represent the demographic data of COVID-19 patients in Indonesia. [ABSTRACT FROM AUTHOR]

What is known and objective: Previous studies based on small‐sample clinical data proved that short‐term use of hypoxia‐inducible factor prolyl hydroxylase (HIF‐PHD) inhibitors increased haemoglobin levels in anaemic patients with chronic kidney disease (CKD). However, these studies reached conflicting conclusions on iron parameters and adverse event profiles. Our meta‐analysis aimed to evaluate the long‐term efficacy and safety of HIF‐PHD inhibitors in renal anaemia. Methods: Randomized controlled trials comparing treatment with HIF‐PHD inhibitors versus placebo or erythropoiesis‐stimulating agents (ESAs) were thoroughly searched in the PubMed, Embase, Cochrane Library and international clinical trial registries. Meta‐analysis was performed on main outcomes with random effects models. Results and discussion: A total of 30 studies comprising 13,146 patients were included. The HIF‐PHD inhibitors used included roxadustat, daprodustat, vadadustat, molidustat, desidustat and enarodustat. HIF‐PHD inhibitors significantly increased haemoglobin levels in comparison with placebo [weighted mean difference (WMD) 1.53, 95% confidence interval (CI) 1.39 to 1.67] or ESAs (WMD 0.13, 95% CI 0.03 to 0.22). Hepcidin, ferritin and serum iron levels were decreased, while total iron binding capacity and transferrin levels were increased in the HIF‐PHD inhibitor group versus those in placebo or ESAs group. Additionally, HIF‐PHD inhibitors medication was associated with cholesterol‐lowering effects. As for safety, the risk of serious adverse events in the HIF‐PHD inhibitor group was increased in comparison with placebo group [risk ratio (RR) 1.07, 95% CI 1.01 to 1.13], but comparable to the ESAs group (RR 1.02, 95% CI 0.94 to 1.10). Compared with placebo, the agents increased the risk of diarrhoea (1.21, 1.00 to 1.47), nausea (1.46, 1.09 to 1.97), oedema peripheral (1.32, 1.01 to 1.59), hyperkalemia (1.27, 1.05 to 1.54) and hypertension (1.34, 1.02 to 1.76). Compared with ESAs, the drugs increased the risk of vomiting (1.30, 1.02 to 1.65), headache (1.27, 1.05 to 1.53) and thrombosis events (1.31, 1.05 to 1.63). What is new and conclusion: HIF‐PHD inhibitors treatment effectively increased haemoglobin levels and promoted iron utilization in anaemic patients with CKD, and they were well tolerated for long‐term use. In order to avoid unfavourable effects of excessive iron consumption, it was appropriate to administer HIF‐PHD inhibitors in combination with iron supplements for long‐term treatment. [ABSTRACT FROM AUTHOR]

Colchicine poisoning is complicated and has a high mortality rate. The aim of this study was to identify the pathogenic characteristics of colchicine poisoning cases and to propose a comprehensive treatment procedure. A total of 43 patients were divided into survival (n = 32) and death groups (n = 11) according to prognosis. The clinical data (basic information, clinical manifestations, laboratory tests, examination results, therapeutic schedule, response evaluation, and prognosis) were analyzed, and the comprehensive treatment was proposed. The ingestion doses were ≤0.5, 0.5-0.8, and ≥0.8 mg/kg, and the survival rates were 100, 83.33, and 28.60%. The causes of death were cardiovascular and bone marrow hematopoietic failures. We found that the order of organ damage was digestive tract, coagulation, muscle, heart, hematopoietic, lung, liver, and kidney, while the recovery order was digestive tract, coagulation, heart, hematopoietic, lung, muscle, kidney, and liver. Different doses of recombinant human granulocyte colony-stimulating factor and recombinant human thrombopoietin can shorten the severity and duration of neutropenia and thrombocytopenia. Plasma exchange combined with continuous veno-venous hemodialysis filtration treatment can increase survival time. The prognosis is positively correlated with the dose. Early removal of toxicants from the digestive tract and blood is essential. It is vital to give comprehensive treatment of multiple organ injuries, include the use of recombinant human granulocyte colony-stimulating factor, recombinant human thrombopoietin, plasma exchange, and continuous veno-venous hemodialysis filtration. [ABSTRACT FROM AUTHOR]

Introduction: Anemia is one of the most common complications of chronic kidney disease (CKD). As a result of the side effects of high doses of recombinant human erythropoietin (rhEPO) and the differences in the standard dose of the injectable iron, this study aimed to evaluate the effect of high and low intravenous iron supplementation on hematinic parameters and EPO requirements in patients under hemodialysis.Methods: This multicenter, randomized, double-blind clinical trial was conducted on 60 patients with CKD admitted to Sina and 29 Bahman hospitals in Tabriz, Iran in 2019-2020 to undergo hemodialysis. In the two studied groups, low (100 mg/week) and high (400 mg/week) doses of iron were administered and subjects were followed up for 6 months. The incidence of acute myocardial ischemia, stroke, and mortality during 6 months was recorded.Results: The required rhEPO dosage (mg/week) to maintain hemoglobin levels between 10 and 12 g/dL in the high-dose iron group was significantly decreased during the follow-up period (52,129.03 ± 23,810 vs. 45,760 ± 20,978.71, P ≤ 0.028). Transferrin saturation (TSAT) index had a significant upward trend after iron injection and significant correlations with the serum levels of Fe (r ≥ 0.353, P ≤ 0.007), ferritin (r ≥ 0.315, P ≤ 0.016), and total iron binding capacity (r ≥ 0.219, P < 0.050) during the follow-up period in the studied groups.Conclusion: High-dose intravenous iron (400 mg/week) can reduce the mean dose of rhEPO requirements and increase the TSAT index over a period of 6 months in hemodialysis patients. High-dose IV iron administration can decrease cardiovascular events in hemodialysis patients with iron deficiency anemia. [ABSTRACT FROM AUTHOR]

Objective: Rare disease Background: Nocardia infections have rarely been reported in hematopoietic stem cell transplantation (HSCT) patients, who usually receive the prophylactic use of sulfamethoxazole/trimethoprim (ST) against Pneumocystis jiroveci. However, the ST prophylaxis, sensitive to Nocardia species, sometimes induces renal toxicities. Therefore, alternative prophylactic or therapeutic drugs are required for nocardiosis in HSCT patients. Case Report: A 34-year-old Japanese man with acute mixed phenotypic leukemia with t(9; 22) received allogenic peripheral blood HSCT from a haplo-identical sibling donor. He developed graft versus host disease (GVHD) with grade II, and was treated with prednisolone and cyclosporine A with concurrent ciprofloxacin, fluconazole, valacyclovir, and ST. However, the prophylactic ST was ceased because of its renal toxicity. He developed a pulmonary nodular lesion with elevated b-D-glucan and Aspergillus galactomannan antigen. Repeated blood and sputum culture isolated no pathogens. Voriconazole treatment administered once improved these lesions and laboratory findings. One month later, he presented with right pleuritic chest pain and multiple ring-enhancing cavitation lesions along the ribs. A needle biopsy demonstrated Nocardia elegans, which is an extremely rare infection induced by Nocardia species, in the cavitation lesions, shown by 16S rRNA gene sequencing. He was started on doripenem and liposomal amphotericin B, and a subsequent treatment kept him free from Nocardia elegans infection, without any adverse effects, while continuing the cyclosporine A and prednisolone treatment for chronic GVHD. Conclusions: Clarithromycin has fewer adverse effects than ST. This case suggests that clarithromycin is an appropriate alternative and prophylactic therapy for patients with nocardiosis and ST toxicities. [ABSTRACT FROM AUTHOR]

Aim: To review the incidence and management of anaemia and outcomes in pregnancies in a cohort of Australian women with chronic kidney disease. Methods: A retrospective audit of 63 pregnancies in 52 women with chronic kidney disease. Results: Sixty-eight percent of chronic kidney disease pregnancies were complicated by haemoglobin less than 100 g/L. Iron stores were measured in only 62% of all pregnancies. Serum ferritin was less than 100 ng/ml in 95% of those tested. Erythropoietin-stimulating agents were used in 24 pregnancies (38%). Intravenous iron was used in only nine non-dialysis pregnancies. Conclusion: Greater awareness of the importance of regular measurement of iron stores and appropriate levels for repletion in chronic kidney disease pregnancies amongst health professionals involved in obstetric care may result in earlier detection and treatment of iron deficiency, and potentially improve maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

Options for anemic lower-risk myelodysplastic syndromes (MDS) without del(5q) after failure of erythropoiesis-stimulating agents (ESAs) are very limited. The effectiveness of second-line treatments is uncertain. We retrospectively reviewed the clinical effectiveness and overall survival (OS) of lower-risk MDS without del(5q) patients exclusively treated with stanozolol (STZ) after failure of epoetin alfa. The response was defined according to the 2006 International Working Group (IWG) criteria. Fifty-six patients were included. The median follow-up time was 55 months (range: 5-156 months). Twenty-seven patients (48.2%) achieved hematologic improvement-erythroid response (HI-E). Higher response rates were observed in patients with lower IPSS-R scores (≤3.5, P = 0.008) and hypocellular bone marrow (P = 0.002). In univariate Cox analysis, HI-E was the strongest factor associated with better OS (P = 0.0003). In multivariate Cox, HI-E, age ≤ 50, and transfusion independence (TI) at the onset of STZ were factors associated with better OS. The estimated 5-year OS was 88.6% (68.7-96.2%) and 33.8% (14.9-54.0%) in responders and non-responders (P < 0.01), respectively. The most common side effects included masculinization and liver damage, but they were manageable with supportive measures and dose adjustments. STZ may be considered an alternative treatment in lower-risk MDS after failure of epoetin alfa. [ABSTRACT FROM AUTHOR]

Luspatercept (Reblozyl®), a first-in-class erythroid maturation agent, is approved in several countries worldwide for the treatment of adults with transfusion-dependent anaemia due to myelodysplastic syndromes (MDS), who have failed prior erythropoiesis-stimulating therapy, or β-thalassaemia. In pivotal, placebo-controlled, phase III trials, subcutaneous luspatercept significantly reduced red blood cell (RBC) transfusion requirements in patients with MDS or β-thalassaemia. Luspatercept had a generally manageable tolerability profile in clinical trials. Adverse events of special interest include thromboembolic events, hypertension and bone pain. Thus, luspatercept is an emerging treatment option in adults with transfusion-dependent anaemia due to MDS or β-thalassaemia. [ABSTRACT FROM AUTHOR]

Background: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production.Methods: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52.Results: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter.Conclusions: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.). [ABSTRACT FROM AUTHOR]

Introduction: Beetroot (Beta vulgaris L.) contains flavonoid compounds that play a role in the haematopoietic process. It is known that methanol extract of beetroot has benefits in the process of haematopoiesis in normal white rats. Aims: To evaluate the beetroot extracts as hematopoietic agents on male rats. Methods: Beetroot dried powder was divided into two parts. One part was macerated separately with dichloromethane and 70% ethanol, while the other part was added with citric acid and washed with water to remove alkaloids and then extracted with 70% ethanol. The study used 24 rats which were divided into four groups. Each group consisted of 6 rats, namely the normal group, dichloromethane extract group, ethanolic extract group, and free alkaloids-ethanolic extract group. Each extract was given at a dose of 200 mg.Kg-1 for 21 days. Analyzed blood parameters are erythrocytes, haemoglobin, MCV, MCH, MCHC, leukocytes, and platelets. The data obtained consisted of the number of cells analyzed using one-way ANOVA then obtained by the Tukey test. Results: This study showed a significant increase in the number of erythrocytes, haemoglobin, MCV, MCH, MCHC, leukocytes, and platelets in rats that were given each extract compared to the normal group (p <0.05). The ethanolic extract of beetroot increased erythrocytes, haemoglobin, MCV, MCH, MCHC, leukocytes, and platelets by 41.49%, 24.95%, 14.92%, 33.54%, 27.19%, 59.40%, and 35.37%, respectively. Conclusions: The ethanolic extract of beetroot has the potential as a good natural haematopoietic agent. [ABSTRACT FROM AUTHOR]

The root of Angelica sinensis (Oliv.) Diels, a well-known Chinese herbal medicine, has been used historically as hematopoietic and anti-inflammatory agents for thousands of years. Recent phytochemistry and pharmacological studies have proved that polysaccharides are one of the major active ingredients in A. sinensis. It has been demonstrated that ASPs (A. sinensis polysaccharides) had various important biological activities, such as hematopoietic, hepatoprotective, hypoglycemic, anti-inflammatory, antitumor, and antioxidant activities. The purpose of this present review is to appraise previous and current literatures on the extraction, purification, structural characterization and biological activities of ASPs. In addition, the structure–activity relationship will be further explored and discussed. We believe that this review will provide a useful bibliography for the investigation, production, and application of ASPs in functional foods and therapeutic agents. Moreover, this review also highlights the challenges of investigation and future considerations for holistic utilization. [ABSTRACT FROM AUTHOR]

The folkloric claim that Cnidoscolus aconitifolius (Chaya) could ameliorate anaemia requires scientific revalidation in anaemic models. The aim of this study is to investigate the anti-anaemic effect of Cnidoscolus aconitifolius on cyclophosphamide-induced anaemia in rats. The leaves of Cnidoscolus aconitifolius were collected, dried and extracted with ethanol. Twenty five Wistar Albino rats weighing 120–180 kg were used. Anaemia was induced in groups 2, 3, 4 and 5 with a single injection of cyclophosphamide, while group 1 served as a negative control without anemia and was treated with 0.5 mL of normal saline, Group 2 rats were treated with 100 mg/kg body weight of Cnidoscolus aconitifolius. Group 3 rats were treated with 500 mg/kg body weight of Cnidoscolus aconitifolius. Group 4 served as the positive control rats and was treated with 0.5 mL of normal saline. Group 5 which served as the standard control rats and were treated with 5 mg/kg body weight of standard drug Chemiron. The treated lasted for two weeks during which blood samples were collected from each rat for haematological analysis. The result shows that hematological parameters were elevated in groups 2, 3 and 5 rats treated with 100 mg/kg and 500 mg/kg body weight of ethanol extract of Cnidoscolus aconitifolius and chemiron respectively. Ethanol leaf extract of Cnidoscolus aconitifolius at a graded dose of 500 mg/kg body weight had higher ameliorative effect on the haematological parameters of cyclophosphamide-induced anemia in rats. [ABSTRACT FROM AUTHOR]

The article offers information about the Thalassemia, a blood disorder that reduces the production of hemoglobin. It mentions that disorder characterized by reduced or no production of hemoglobin and chronic anemia of varying severity. It discusses that challenges to the implementation of prevention programs and improved newborn survival have translated to continued burden of incident disease in both resource-limited regions and multiethnic cities in developed countries.

Background/purpose: Our previous study found the serum gastric parietal cell antibody (GPCA) positivity in 12.3% of burning mouth syndrome (BMS) patients. This study assessed whether GPCA-positive BMS (GPCA+BMS) patients had significantly higher frequencies of macrocytosis, anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-negative BMS (GPCA-BMS) patients.Methods: The mean corpuscular volume, blood hemoglobin (Hb), and serum iron, vitamin B12, folic acid, homocysteine, and GPCA levels were measured and compared between any two of three groups of 109 GPCA+BMS patients, 775 GPCA-BMS patients, and 442 healthy control subjects.Results: We found that 109 GPCA+BMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron and vitamin B12 deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.001) and significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than 775 GPCA-BMS patients (all P-values < 0.01). Moreover, 775 GPCA-BMS patients had significantly higher frequencies of macrocytosis, blood Hb and serum iron, vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia than 442 healthy control subjects (all P-values < 0.005). Pernicious anemia (45.5%) and normocytic anemia (24.2%) were the two most common types of anemia in 33 anemic GPCA+BMS patients. Moreover, normocytic anemia (61.3%), thalassemia trait-induced anemia (15.5%), and iron deficiency anemia (14.1%) were the three most common types of anemia in 142 anemic GPCA-BMS patients.Conclusion: GPCA+BMS patients have significantly higher frequencies of macrocytosis, blood Hb and serum vitamin B12 deficiencies, and hyperhomocysteinemia than healthy control subjects or GPCA-BMS patients. [ABSTRACT FROM AUTHOR]

Background: Patients in maintenance hemodialysis (HD) need a patent vascular access for optimal treatment. The recommended first choice is a native arteriovenous fistula (AVF). Complications of AVF are frequent and include thrombosis, stenosis and infections leading to worsening of dialysis efficacy. Some known risk factors are age, gender and the presence of diabetes mellitus. The aim was to investigate if further risk variables are associated with dysfunctional AVF.Methods: This retrospective observational study included 153 chronic HD patients (Cases) referred to a total of 473 radiological investigations due to clinically suspected complications of their native AVF. Another group of chronic HD patients (n = 52) who had a native AVF but were without history of previous complications for at least 2 years were controls. Statistical analyses included ANOVA, logistic regression, parametric and non-parametric methods such as Student's T-test and Mann-Whitney test.Results: Among Cases, at least one significant stenosis (> 50% of the lumen) was detected in 348 occasions. Subsequent PTA was performed in 248 (71%). Median erythropoiesis-stimulating agent (ESA) weekly doses were higher in Cases than in Controls (8000 vs 5000 IU, p < 0.001). Cases received higher doses of intravenous iron/week than the Controls before the investigation (median 50 mg vs 25 mg, p = 0.004) and low molecular weight heparin (LMWH, p = 0.028). Compared to Controls, Cases had a lower level of parathyroid hormone (median 25 vs 20 ρmol/L, p = 0.009). In patients with diabetes mellitus, HbA1c was higher among Cases than Controls (50 vs 38 mmol/mol, p < 0.001). Multiple regression analysis revealed significant associations between Cases and female gender, prescription of doxazocin, and doses of ESA and LMWH. There was no difference between the groups regarding hemoglobin, CRP or ferritin.Conclusion: In conclusion, the present study indicated that the factors associated with AVF problems were high doses of ESA, iron administration, and tendency of thromboembolism (indicated by high LMWH doses); the use of doxazocin prescription, however, requires further investigation. [ABSTRACT FROM AUTHOR]

β‐Thalassemia is an inherited blood disorder resulting from defects in hemoglobin production, leading to premature death of red blood cells (RBCs) or their precursors. Patients with transfusion‐dependent β‐thalassemia often need lifelong regular RBC transfusions to maintain adequate hemoglobin levels. Frequent transfusions may lead to iron overload and organ damage. Thus, there is a large unmet need for alternative therapies. Luspatercept, a first‐in‐class erythroid maturation agent, is the first approved therapy in the United States for the treatment of anemia in adult patients with β‐thalassemia who require regular RBC transfusions. The population pharmacokinetics and exposure‐response relationship of luspatercept were evaluated in 285 patients with β‐thalassemia. Luspatercept displayed linear and time‐invariant pharmacokinetics when administered subcutaneously once every 3 weeks. Body weight was the only clinically relevant covariate of luspatercept clearance, favoring weight‐based dosing. Magnitude and frequency of hemoglobin increase, if not influenced by RBC transfusions, was positively correlated with luspatercept area under the serum concentration‐time curve (AUC), 0.2‐1.25 mg/kg, whereas a significant reduction in RBC units transfused was observed in frequently transfused patients. The probability of achieving ≥33% or ≥50% reduction in RBC transfusion burden was similar across the time‐averaged AUC (0.6‐1.25 mg/kg), with the 1 mg/kg starting dose sufficient for most early responders (71%‐80%). Increasing luspatercept AUC (0.2‐1.25 mg/kg) did not increase incidence or severity of treatment‐emergent adverse events. These results provide a positive benefit‐risk profile for the recommended luspatercept doses (1‐1.25 mg/kg) in treating adult patients with β‐thalassemia who require regular RBC transfusions. [ABSTRACT FROM AUTHOR]

The article discusses the successful withdrawal of erythropoiesis-stimulating agent after administration of an SGLT2 inhibitor, tofogliflozin, in people with diabetes. Topics include determine whether the administration of an SGLT2 inhibitor is associated with successful withdrawal of erythropoiesis-stimulating agent (ESA) in people with type 2 diabetes and renal anaemia; and ESA withdrawal was considered successful when its administration was discontinued after the start of tofogliflozin.

To increase the success in Covid 19 treatment, many drug suggestions are presented, and some clinical studies are shared in the literature. There have been some attempts to use some of these drugs in combination. However, using more than one drug together may cause serious side effects on patients. Therefore, detecting drug-drug interactions of the drugs used will be of great importance in the treatment of Covid 19. In this study, the interactions of 8 drugs used for Covid 19 treatment with 645 different drugs and possible side effects estimates have been produced using Graph Convolutional Networks. As a result of the experiments, it has been found that the hematopoietic system and the cardiovascular system are exposed to more side effects than other organs. Among the focused drugs, Heparin and Atazanavir appear to cause more adverse reactions than other drugs. In addition, as it is known that some of these 8 drugs are used together in Covid-19 treatment, the side effects caused by using these drugs together are shared. With the experimental results obtained, it is aimed to facilitate the selection of the drugs and increase the success of Covid 19 treatment according to the targeted patient. [ABSTRACT FROM AUTHOR]

Trials studying iron administration in patients with chronic heart failure (CHF) and iron deficiency (ID) have sprung up these years but the results remain inconsistent. The aim of this meta-analysis was to comprehensively evaluate the efficacy and safety of iron therapy in patients with CHF and ID. A literature search was conducted across PubMed, Embase, Cochrane Library, OVID and Web of Science up to 31 July 2019 to search for randomised controlled trials (RCT) comparing iron therapy with placebo in CHF with ID, regardless of presence of anaemia. Published studies reporting data of any of the following outcomes were included: all-cause death, cardiovascular hospitalisation, adverse events, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), N-terminal pro b-type natriuretic peptide, peak oxygen consumption, 6 min walking test (6MWT) distance and quality of life (QoL) parameters. 15 RCTs with a total of 1627 patients (911 in iron therapy and 716 in control) were included. Iron therapy was demonstrated to reduce the risk of cardiovascular hospitalisation (OR 0.35, 95% CI 0.12 to 0.99, p=0.049), but was ineffective in reducing all-cause death (OR 0.59, 95% CI 0.33 to 1.06, p=0.078) or cardiovascular death (OR 0.80, 95% CI 0.39 to 1.63, p=0.540). Iron therapy resulted in a reduction in NYHA class (mean difference (MD) -0.73, 95% CI -0.99 to -0.47, p<0.001), an increase in LVEF (MD +4.35, 95% CI 0.69 to 8.00, p=0.020), 6MWT distance (MD +35.44, 95% CI 11.55 to 59.33, p=0.004) and an improvement in QoL: EQ-5D score (MD +4.07, 95% CI 0.84 to 7.31, p=0.014); Minnesota Living With Heart Failure Questionnaire score (MD -19.47, 95% CI -23.36 to -15.59, p<0.001) and Patients Global Assessment (PGA) scale (MD 0.71, 95% CI 0.32 to 1.10, p<0.001). There was no significant difference in adverse events or serious adverse events between iron treatment group and control group. Iron therapy reduces cardiovascular hospitalisation in patients with CHF with ID, and additionally improves cardiac function, exercise capacity and QoL in patients with CHF with ID and anaemia, without an increase of adverse events. [ABSTRACT FROM AUTHOR]

SUMMARY: Background: Identifying erythropoiesis‐stimulating agent (ESA) resistance is important for treating reversible causes, reaching target haemoglobin levels with minimal dosing, avoiding adverse effects and reducing costs. The resistance index (RI, dose/kg weight/g haemoglobin/dl) is reportedly superior to absolute or weight‐based dosing. Objectives: With the growing number of ESA classes and medications, our goal was to develop methodology to establish RI ranges in otherwise healthy haemodialysis patients as a structured approach to identify remediable causes of anaemia. Design: We retrospectively studied anaemia management with darbepoetin in 100 chronic haemodialysis patients and a subgroup of 48 without identifiable conditions that impair erythropoiesis. Data included inflammatory and bone marrow conditions, medications with hematologic effects, catheter use, iron, parathyroid and dialysis measures. Results: The haematologically healthy group was aged 57.1 ± 1.9 SEM years, 33% diabetic, with haemoglobin 10.4 ± 0.2 g/dl. The darbepoetin RI (DRI) values were 0.05 ± 0.01, absolute dose 38.5 ± 3.5 mcg/week and weight‐based 0.50 ± 0.05 mcg/kg. Regression analyses included iron saturation, ferritin, parathyroid hormone and urea reduction ratio. DRI was superior to other dosing approaches based on the distribution of results (kurtosis) and discordance between the measures that occurred in 17% of patients at haemoglobin target. Conclusions: We demonstrate the value of determining the RI for use with expanding ESA choices, using as an example how DRI values can be established for healthy haemodialysis patients so as to guide dosing. When elevated, the RI can trigger evaluation for remediable factors causing hyporesponsiveness even when haemoglobin goals have been reached. [ABSTRACT FROM AUTHOR]

A group of renal experts attended a round-table meeting to discuss anaemia in chronic kidney disease. Here, Jasmine Callaghan, Journal of Kidney Care (JKC) Editor, details the outcomes [ABSTRACT FROM AUTHOR]