Search

Abstract: The ACE-536-MF-001 trial enrolled patients with myelofibrosis (n = 95) into 4 cohorts: patients in cohorts 1 and 3A were non-transfusion dependent (NTD) and had anemia; patients in cohorts 2 and 3B were transfusion dependent (TD); and patients in cohort 3A/3B had stable ruxolitinib treatment before and during the study. All patients received luspatercept (1.0-1.75 mg/kg, 21-day cycles). Treatment was extended if clinical benefit was observed at day 169. The primary end point was anemia response rate (NTD, ≥1.5 g/dL hemoglobin increase from baseline; TD, transfusion-independence) over any 12-week period during the primary treatment period (weeks 1-24). Overall, 14% of patients in cohorts 1 and 3A, 10% in cohort 2, and 26% in cohort 3B met the primary end point. In cohorts 1 and 3A (NTD), 27% and 50% of patients, respectively, had mean hemoglobin increase of ≥1.5 g/dL from baseline. Among TD patients, ∼50% had ≥50% reduction in transfusion burden. Reduction in total symptom score was observed in all cohorts, with the greatest response rate seen in cohort 3A. Overall, 94% of patients had ≥1 adverse event (AE); 47% had ≥1 treatment-related AE (TRAE; 11% grade ≥3), most frequently hypertension (18%), managed with medical intervention. One patient had a serious TRAE leading to luspatercept discontinuation. Nine patients died on treatment (unrelated to study drug). In most patients, ruxolitinib dose and spleen size remained stable. In patients with myelofibrosis, luspatercept improved anemia and transfusion burden across cohorts; the safety profile was consistent with previous studies. This trial was registered at www.ClinicalTrials.gov as #NCT03194542., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

We investigated herein the prevalence of Fasciola hepatica infection in sheep at Sejnane slaughterhouse, governorate of Bizerte, Northwest of Tunisia, using three different diagnostic techniques (liver dissection, bile examination, and coprology). Faeces, liver, gall bladder as well as blood samples were collected from 603 slaughtered sheep in two seasons: winter and summer. Faecal egg counts of F. hepatica were estimated using sedimentation technique. Livers were examined for the presence of flukes, and bile collected from gall bladder was examined by sedimentation technique for the presence of F. hepatica eggs. Faecal egg counts of gastrointestinal helminths were estimated using flotation followed by the McMaster technique. Blood samples were used to estimate blood cell count (RBC) (×10 6 /mL), haemoglobin (Hb) (g/dL), and haematocrit (Ht) (%) levels. A total of 1714 F. hepatica flukes were collected from 68 infected livers, the number of flukes per sheep ranged between naught and 195. Bile examination (16.78% ± 1.83; 51/310) showed the higher infection prevalence, followed by liver dissection (11.28% ± 1.17; 68/603) and coprology (9.12% ± 1.08; 55/603) (p = 0.015). Infection prevalences were significantly higher in young sheep aged of less than 1 year (8.13% ± 1.22; 49/498), in cross-bred sheep (10.61% ± 1.39%; 64/478), and in summer (7.13% ± 1.82; 43/293) (p < 0.05). There was no significant difference in infection prevalence by gastrointestinal helminths in F. hepatica-infected and F. hepatica-non-infected animals (p > 0.05). The overall prevalence of F. hepatica-infected anaemic sheep was higher (22.73% ± 4.47; 20/88) than F. hepatica-non-infected anaemic sheep (p < 0.05). Fasciola hepatica infection is frequent in sheep from Sejnane representing hence an important constraint for the development of the sheep industry in this region. Therefore, it is necessary to establish and implement a specific control programme to reduce fasciolosis infection risks including animal owners' education., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Objectives: Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome., Methods: This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied., Results: One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20 g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients., Conclusion: Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points • Thrombocytopenia is the hallmark laboratory finding in CAPS. • A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. • Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Background: The preplanned interim analysis of the COMMANDS trial showed greater efficacy of luspatercept than epoetin alfa for treating anaemia in erythropoiesis-stimulating agent (ESA)-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. In this Article, we report the results of the primary analysis of the trial., Methods: COMMANDS is a phase 3, open-label, randomised, controlled trial conducted at 142 sites in 26 countries. Eligible patients were those aged 18 years or older, with myelodysplastic syndromes of very low risk, low risk, or intermediate risk (as defined by the Revised International Prognostic Scoring System), who were ESA-naive and transfusion dependent, and had a serum erythropoietin concentration of less than 500 U/L. Patients were stratified by baseline red blood cell transfusion burden, serum erythropoietin concentration, and ring sideroblast status, and randomly allocated (1:1) to receive luspatercept (1·0-1·75 mg/kg body weight, subcutaneously, once every 3 weeks) or epoetin alfa (450-1050 IU/kg body weight, subcutaneously, once a week; maximum total dose 80 000 IU) for at least 24 weeks. The primary endpoint was red blood cell transfusion independence lasting at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), evaluated in the intention-to-treat population. The safety population included all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov (NCT03682536; active, not recruiting)., Findings: Between Jan 2, 2019, and Sept 29, 2022, 363 patients were screened and randomly allocated: 182 (50%) to luspatercept and 181 (50%) to epoetin alfa. Median age was 74 years (IQR 69-80), 162 (45%) patients were female, and 201 (55%) were male. 289 (80%) were White, 44 (12%) were Asian, and two (1%) were Black or African American. 23 (6%) were Hispanic or Latino and 311 (86%) were not Hispanic or Latino. Median follow-up for the primary endpoint was 17·2 months (10·4-27·7) for the luspatercept group and 16·9 months (10·1-26·6) for the epoetin alfa group. A significantly greater proportion of patients in the luspatercept group reached the primary endpoint (110 [60%] vs 63 [35%]; common risk difference on response rate 25·4% [95% CI 15·8-35·0]; p<0·0001). Median follow-up for safety analyses was 21·4 months (IQR 14·2-32·4) for the luspatercept group and 20·3 months (12·7-30·9) for the epoetin alfa group. Common grade 3-4 treatment-emergent adverse events occurring among luspatercept recipients (n=182) were hypertension (19 [10%] patients), anaemia (18 [10%]), pneumonia (ten [5%]), syncope (ten [5%]), neutropenia (nine [5%]), thrombocytopenia (eight [4%]), dyspnoea (eight [4%]), and myelodysplastic syndromes (six [3%]); and among epoetin alfa recipients (n=179) were anaemia (14 [8%]), pneumonia (14 [8%]), neutropenia (11 [6%]), myelodysplastic syndromes (ten [6%]), hypertension (eight [4%]), iron overload (seven [4%]), and COVID-19 pneumonia (six [3%]). The most common serious treatment-emergent adverse events in both groups were pneumonia (nine [5%] luspatercept recipients and 13 [7%] epoetin alfa recipients) and COVID-19 (eight [4%] luspatercept recipients and ten [6%] epoetin alfa recipients). One death (due to acute myeloid leukaemia) considered to be luspatercept-related was reported at the interim analysis., Interpretation: Luspatercept represents a new standard of care for ESA-naive patients with transfusion-dependent, lower-risk myelodysplastic syndromes. Significantly more patients had red blood cell transfusion independence and haematological improvement with luspatercept than with epoetin alfa, with benefits observed across patient subgroups., Funding: Celgene and Acceleron Pharma., Competing Interests: Declaration of interests Editorial and medical writing support were funded by Bristol Myers Squibb. MGDP reports receiving honoraria from and advisory or data safety monitoring board fees from Bristol Myers Squibb. GG-M reports receiving consulting fees from Bristol Myers Squibb; research support from AbbVie, Astex, Bristol Myers Squibb, Chordia, Curis, Genentech, Novartis, Rigel Pharmaceuticals, and Zentalis; and honoraria from Astex and Curis. VS reports receiving honoraria from AbbVie, Bristol Myers Squibb, and Novartis; travel support from AbbVie and Jazz Pharmaceuticals; and advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, CTI BioPharma, Curis, Geron, Gilead, Keros, Menarini, Novartis, Servier, and Syros. AMZ reports receiving grant support from AbbVie, Amgen, Astex, Bristol Myers Squibb, Celgene, Geron, Kura, Novartis, Otsuka, Shattuck Labs, and Syros; and consulting fees and honoraria from AbbVie, Agios, Akeso Pharma, ALX Oncology, Amgen, Astellas Pharma, BeiGene, BioCryst, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Chiesi, Daiichi Sankyo, Epizyme, Faron, Genentech, Geron, Gilead, Glycomimetics, Hikma, Janssen, Karyopharma, Keros, Kura, Kyowa Kirin, Lava Therapeutics, Medus, Notable, Novartis, Orum, Otsuka, Pfizer, Regeneron, Rigel Pharmaceuticals, Schrodinger, Servier, Sumitomo Pharma, Syndax, Syros, Taiho, Takeda, Treadwell, Vincerx, and Zentalis. RSK reports receiving grant support from Bristol Myers Squibb; consulting fees from Geron, Janssen, and Sumitomo Pharma; speakers bureau fees from AbbVie, Jazz Pharmaceuticals, Pharma Essentia, Rigel Pharmaceuticals, Servio, and Sobi; and advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, DSI, Jazz Pharmaceuticals, Pharma Essentia, Rigel Pharmaceuticals, Servio, Sobi, and Sumitomo Pharma. JS reports receiving grant support from Amgen Australia, Astex Pharmaceuticals, and Bristol Myers Squibb; consulting fees paid to himself from Astellas Pharma, Mundipharma, Novartis, Otsuka, and Pfizer; speakers bureau fees paid to himself and his institution from Mundipharma and Novartis; support for meeting attendance from AstraZeneca (no payment to healthcare provider); being a named investigator on patent PCT/AU2021/050562 assigned to his institution; trial steering committee fees paid to his institution from Bristol Myers Squibb; and serving an unpaid appointment on the Australasia Leukaemia and Lymphoma Group Scientific Advisory Committee. DV reports receiving consulting fees from Amgen, Astellas Pharma, Bristol Myers Squibb, Jazz Pharmaceuticals, Kite Pharma, Merck Sharp & Dohme, Novartis, Sanofi, and Sobi; honoraria from Agios, Amgen, Astellas Pharma, Bristol Myers Squibb, Gebro, Grifols, Janssen, Jazz Pharmaceuticals, Kite Pharma, Merck Sharp & Dohme, Novartis, Pfizer, Sanofi, and Sobi; travel support from Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Sanofi, and Sobi; and advisory or data safety monitoring board fees from Amgen, Bristol Myers Squibb, Grifols, Jazz Pharmaceuticals, Novartis, Servier, and Sobi. AJ reports receiving support for study materials from Bristol Myers Squibb; consulting fees from Bristol Myers Squibb; honoraria from AbbVie, Bristol Myers Squibb, and Novartis; travel support from AbbVie and Novartis; advisory or data safety monitoring board fees from AbbVie, Bristol Myers Squibb, GSK, and Novartis; and a leadership or fiduciary role as the head of the Czech MDS Group. JL, RP, SK, KLK, TP, and YL are employed by and own stock in Bristol Myers Squibb. JZ is employed by Bristol Myers Squibb. VP is employed by and owns stock in Bristol Myers Squibb and owns stock in Merck. SR is employed by, owns stock in, and has received travel support from Bristol Myers Squibb and owns stock in Celgene. AD reports receiving honoraria from Bristol Myers Squibb; travel support from Johnson & Johnson; and advisory or data safety monitoring board fees from Swixx BioPharma. TC reports receiving consulting fees from AbbVie, Agios, BluePrint, Bristol Myers Squibb/Celgene, Jazz Pharmaceuticals, Novartis, and Servier; honoraria from Astellas, Bristol Myers Squibb/Celgene, Incyte, Jazz Pharmaceuticals, Novartis, Servier, and Takeda; travel support from AbbVie, Bristol Myers Squibb/Celgene, Gilead, Novartis, Pfizer, and Servier; and advisory or data safety monitoring board fees from Astellas, Bristol Myers Squibb/Celgene, Incyte, Jazz Pharmaceuticals, Novartis, Servier, and Takeda. PF reports receiving grant support from AbbVie, Agios, Bristol Myers Squibb, and Novartis; and honoraria from AbbVie, Agios, Bristol Myers Squibb, and Novartis. UP reports receiving grant support paid to GWT-TUD, from Amgen and Janssen; grant support, paid to University of Leipzig, from Bristol Myers Squibb, Merck, and Novartis; consulting fees from AbbVie, Bristol Myers Squibb, Curis, Geron, Janssen, and Novartis; honoraria from Bristol Myers Squibb and Novartis; and fees for serving on a steering committee and travel support from Bristol Myers Squibb. All other authors declare no competing interests., (2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Introduction: Ineffective erythropoiesis and subsequent anemia as well as primary and secondary (transfusional) iron overload are key drivers for morbidity and mortality outcomes in patients with β-thalassemia., Areas Covered: In this review, we highlight evidence from observational studies evaluating the association between measures of anemia and iron overload versus outcomes in both non-transfusion-dependent and transfusion-dependent forms of β-thalassemia., Expert Opinion: Several prognostic thresholds have been identified with implications for patient management. These have also formed the basis for the design of novel therapy clinical trials by informing eligibility and target endpoints. Still, several data gaps persist in view of the challenge of assessing prospective long-term outcomes in a chronic disease. Pooling insights on the prognostic value of different measures of disease mechanism will be key to design future scoring systems that can help optimize patient management.

Posterior reversible encephalopathy syndrome (PRES) is an increasingly recognized clinical entity associated with a variety of medical conditions. It is commonly considered in the presentation of uncontrolled, severe hypertension. However, more recently, it has been described in the setting of blood transfusion, particularly in those with chronic anemia, even in the absence of severe hypertension. We describe a patient who presented to the emergency department 12 days after large blood transfusion for severe, chronic anemia with headache, vision loss, expressive aphasia and a change in mental status, with only mild blood pressure elevation, who was ultimately diagnosed with PRES and refractory non-convulsive status epilepticus. Emergency physicians are often the first to initiate blood transfusion for those with a low hemoglobin. Therefore, it is prudent to proceed with caution in transfusing those with chronic anemia. It is also important for the emergency physician to keep PRES on the differential for those presenting with a neurologic complaint after correction of their chronic anemia, even in the absence of severe hypertension., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration., Methods: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively., Results: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower., Conclusion: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies., Trial Registration: ClinicalTrials.gov: NCT02101268., (© 2024. Crown.)

Myelofibrosis is a rare and often fatal hematological neoplasm, and the treatment of myelofibrosis-associated anemia remains suboptimal, with no improved therapies. Luspatercept was shown to display some efficacy in a phase 2 clinical trial for Myelofibrosis with anemia, yet relevant research are limited. Threrfore, data from patients diagnosed with refractory anemic primary or post-essential thrombocythemia/polycythemia vera myelofibrosis, who were treated with luspatercept for at least 9 weeks, were retrospectively collected. Eighteen patients with myelofibrosis treated with luspatercept were enrolled. Median age was 68 years (range, 44-80 years), and 27.8% were males. Ten (55.6%) were transfusion-dependent. Ten (55.6%) were Dynamic International Prognostic Scoring System intermediate-1, and eight (44.4%) were intermediate-2. The median follow-up was 7 (4-16) months. Erythroid response occurred in eight patients (44.4%) at week 12, four patients (30.8%) at week 24, and nine (50%) at the end of follow-up. Patients who were transfusion-dependent and not transfusion-dependent had similar HI-E responses, at different time points (P > 0.05). Patients had a significantly higher hemoglobin level at 12 weeks, 24 weeks, and at the end of follow-up, than at baseline (P = 0.001, P = 0.021, and P = 0.005, respectively). Treatment-related adverse events occurred in five (16.7%) patients, with no serious adverse events. Two (11.1%) patients relapsed at weeks 15 and 31. One patient progressed to acute myeloid leukemia. No patients had died by the end of follow-up. Luspatercept induced a good response in patients with anemic myelofibrosis, with a low relapse rate and good tolerance., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The RIDART I study found a 13.6% prevalence of anemia in Italian patients with inflammatory bowel disease (IBD); most cases were due to iron-deficiency anemia (IDA)., Aims: To evaluate changes in hemoglobin concentration during a 24-week follow-up of anemic patients with IBD., Methods: Follow-up laboratory and clinical data were obtained from RIDART I study patients with anemia. Factors affecting hemoglobin concentration, the impact of anemia on fatigue and quality of life (QoL), and its relationship with treatment, disease activity and disease complications were investigated., Results: Hemoglobin was 108 g/L at baseline, increased to 121 g/L at follow-up week 12 (p < 0.001) and then stabilized until week 24, but most patients remained anemic, with IDA, throughout the study. Hemoglobin improvement was greater in patients receiving either oral or parenteral iron supplementation. Following hemoglobin normalization, anemia relapse rate during follow-up was 30%. Oral iron did not cause disease reactivation. Lower follow-up hemoglobin was associated with a higher probability of having active disease, clinical complications, increased fatigue and reduced QoL., Conclusions: In anemic patients with IBD, anemia represents a long-lasting problem, in most cases persisting for up to 24 weeks, with high relapse rate and a negative impact on fatigue and QoL., Competing Interests: Conflict of interest The Authors have no conflict of interest to declare. No specific funding. This work was supported by the Italian Group for Inflammatory Bowel Diseases (IG-IBD); the Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Pavia; and the University of Pavia, Pavia, Italy. No specific funding was obtained., (Copyright © 2024. Published by Elsevier Ltd.)

Anemia-directed therapeutic approaches targeting the TGF-β-SMAD and HIF-PH pathways., (© 2024 Wiley Periodicals LLC.)

Competing Interests: Conflicts of interest None disclosed.

Malaria, a parasitic infection caused by the genus Plasmodium, results to over 20 million reported cases annually worldwide. Most individuals exhibit various symptoms, and blood analysis plays a crucial role in determining the appropriate treatment approach. This study discusses various hematologic complications associated with different Plasmodium species. A review of scientific databases including PubMed, Science Direct, Web of Science, Scopus, EMBASE, Magiran, SID, IranMedex was conducted using standard keywords such as Plasmodium, malaria, anemia and blood disorders (hematologic disorder) between 2000 and 2024. The review focused on articles pertaining to clinical trials, prospective cohort, retrospective, cross-sectional and case-control studies. Articles evaluating the effects of malaria on blood cells and indices, with target groups including human and animals, were included. Articles not written in English or Farsi were excluded. Our review revealed that, apart from iron deficiency anemia and vascular dysfunction contributed in part by adhesion of infected RBC to endothelium, decreases in hematocrit and hemoglobin levels, as part of pancytopenia and thrombocytopenia, are characteristic of Plasmodium infection. Additionally, the occurrence of inflammation due to the release of inflammatory cytokines and complement activation can complicate the clinical features of malaria in individuals with hematologic conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To explore the potential of testosterone therapy in managing cytopenias in myelodysplastic neoplasm and investigate the link between hypogonadism and hematologic malignancies., Methods: A case of a patient with intermediate-risk myelodysplastic neoplasm and hypogonadism treated with testosterone replacement therapy is presented. Testosterone, prostate specific antigen, and erythropoietin levels were checked prior to therapy initiation and 3 months after. Blood counts were monitored over time. This is followed by a literature review of testosterone use in myelodysplastic neoplasm and the prevalence of hypogonadism in hematologic malignancies., Results: The patient showed sustained improvement in anemia with testosterone therapy and reported subjective improvement in his weakness and fatigue. This improvement occurred even in the setting of an undetectable follow up erythropoietin level. His repeat prostate specific antigen levels remained low, while testosterone levels showed marked improvement. The literature review demonstrated positive response rates for testosterone in treating myelodysplastic neoplasm-related cytopenias, and showed a higher incidence of hypogonadism in hematologic malignancies., Conclusion: Our review suggests that the use of testosterone in low and intermediate-risk myelodysplastic neoplasm is underexplored and poses to have significant potential as a future therapeutic agent, after careful consideration of risks and benefits. In addition, the incidence of hypogonadism in myelodysplastic neoplasm and its potential impact on exacerbating cytopenias in myelodysplastic neoplasm warrants further investigation., (© 2024. The Author(s).)

Background: Plasmodium falciparum infection is associated with the human ABO blood group. However, there is a paucity of data on the role that ABO and Rhesus blood groups play in malaria clinical presentations. Therefore, the objective of this study was to assess the association of human ABO blood groups and the Rhesus blood (Rh) types with the severity of malaria., Methods: This cross-sectional study was carried out at the Suhum Government Hospital in the Eastern region of Ghana. Conveniently, study participants with malaria, diagnosed by microscopy, were selected into the study. Subsequently, their ABO and Rh blood groups were determined (Accucare ABO/Rh monoclonal antibodies, Chennai, India). Malaria severity was assessed using the criteria for assessing severe malarial anaemia published by the World Health Organization. According to the criteria, severe malarial anaemia was classified as having haemoglobin (Hb) < 5 g/dL for children < 12 years and in patients ≥ 12 years, Hb level < 7 g/dL, with parasitaemia > 10,000/µL in both cases. Severe malarial anaemia was also classified as having plasma bilirubin > 50 µmol/L with parasitaemia ≥ 100,000/µL, for all ages. Chi square statistical analysis was used to test the association between the blood groups and the clinical or laboratory findings, while multivariate analysis was performed to identify which blood groups were more vulnerable to develop severe malarial anaemia., Results: Of the total number of the study participants (n = 328), most of the patients had blood group O Rh positive (35.7%) while few of them had blood group AB Rh negative (2.1%). The types of Rhesus did not associate with malaria. However, compared to blood group O, the odds of developing severe malarial anaemia, in children < 12 years and in patients ≥ 12 years, were 16 times and 17.8 times higher among patients with blood group A, respectively. Furthermore, the odds of having bilirubin level > 50 µmol/L with parasitaemia ≥ 100,000 /µL was 10 times higher among patients with blood groups A and 2.6 times higher in patients with blood group B, compared to blood group O. Finally, in patients with blood group A majority (71.6%) of them developed high temperature (> 37.5 °C) while 43.3% of them vomited and had diarrhoea. However, pallor (group B = 46.2% vs group A = 37.3%), fever (group B = 84.6% vs group A = 79.1%) and nausea (group B = 46.2% vs group A = 25.4%) were more frequent in patients with blood group B than A., Conclusions: This study found that people with blood groups A and B were severely affected by malaria, with group A being the most vulnerable. It is recommended that blood group assessment be performed for all patients with malaria. Patients found to have blood group A or B must be promptly and efficiently managed to avoid the development of severe malaria anaemia., (© 2024. The Author(s).)

Background: The effect of a liberal transfusion strategy as compared with a restrictive strategy on outcomes in critically ill patients with traumatic brain injury is unclear., Methods: We randomly assigned adults with moderate or severe traumatic brain injury and anemia to receive transfusion of red cells according to a liberal strategy (transfusions initiated at a hemoglobin level of ≤10 g per deciliter) or a restrictive strategy (transfusions initiated at ≤7 g per deciliter). The primary outcome was an unfavorable outcome as assessed by the score on the Glasgow Outcome Scale-Extended at 6 months, which we categorized with the use of a sliding dichotomy that was based on the prognosis of each patient at baseline. Secondary outcomes included mortality, functional independence, quality of life, and depression at 6 months., Results: A total of 742 patients underwent randomization, with 371 assigned to each group. The analysis of the primary outcome included 722 patients. The median hemoglobin level in the intensive care unit was 10.8 g per deciliter in the group assigned to the liberal strategy and 8.8 g per deciliter in the group assigned to the restrictive strategy. An unfavorable outcome occurred in 249 of 364 patients (68.4%) in the liberal-strategy group and in 263 of 358 (73.5%) in the restrictive-strategy group (adjusted absolute difference, restrictive strategy vs. liberal strategy, 5.4 percentage points; 95% confidence interval, -2.9 to 13.7). Among survivors, a liberal strategy was associated with higher scores on some but not all the scales assessing functional independence and quality of life. No association was observed between the transfusion strategy and mortality or depression. Venous thromboembolic events occurred in 8.4% of the patients in each group, and acute respiratory distress syndrome occurred in 3.3% and 0.8% of patients in the liberal-strategy and restrictive-strategy groups, respectively., Conclusions: In critically ill patients with traumatic brain injury and anemia, a liberal transfusion strategy did not reduce the risk of an unfavorable neurologic outcome at 6 months. (Funded by the Canadian Institutes of Health Research and others; HEMOTION ClinicalTrials.gov number, NCT03260478.)., (Copyright © 2024 Massachusetts Medical Society.)

Competing Interests: Competing interests: None to declare.

Objective: Chronic kidney disease (CKD)-associated anaemia has substantial biopsychosocial impacts. This study explores the impact of CKD-associated anaemia and treatment preferences from the patient perspective., Design: Cross-sectional survey., Setting: Anonymised online survey implemented by Ipsos UK on behalf of the National Kidney Federation and GSK from October 2022 to January 2023., Participants: Data were collected from UK adults living with CKD (self-reported)., Primary and Secondary Outcome Measures: Outcome measures were exploratory and not predefined. The cross-sectional survey was designed to explore the biopsychosocial impact of living with anaemia on individuals with CKD; their unmet needs; the treatment strategies typically implemented and the associated barriers/facilitators to adherence; the healthcare professional-patient relationship with regard to anaemia diagnosis and management., Results: Of 101 participants, 90 (89%) were patients with CKD and 11 (11%) were informal carers. 96 (95%) participants reported symptom(s) relevant to their experience of CKD. 88 (87%) participants reported symptom(s) associated with anaemia and 61 (64%) expressed an impact on daily life including 18 (19%) unable to perform daily activities, 13 (14%) unable to go to work and 9 (9%) reporting poor social life/interactions. 85 (84%) participants reported they have received treatment for anaemia: intravenous iron (n=55, 54%), iron tablets (n=29, 29%), erythropoietin-stimulating agents (ESAs) via an autoinjector (n=28, 28%), ESA injections via a syringe (n=24, 24%), ESA injections via a dialysis machine (n=17, 17%), folic acid (n=22, 22%) and blood transfusion (n=17, 17%). Six of seven (86%) participants who received their ESA from a healthcare professional at home preferred injections whereas 13/27 (48%) participants who injected themselves at home preferred oral tablets., Conclusions: There is not a 'one-size-fits-all' approach to the management of CKD-associated anaemia. A personalised approach incorporating the treatment preferences of the individual should be explored when discussing treatment options., Competing Interests: Competing interests: KLH and PR declare no conflicts of interest. JR is an employee of Ipsos and received honoraria for speaking as part of a GSK panel at UK Kidney Week 2023 congress and for an internal seminar delivered to Astellas. CC and MM are employees of and hold shares in GSK. JK was an employee of GSK at the time of the study and is currently an employee of Medice UK Ltd. SP is an employee of Ipsos. JOB received payment for participating in speaker’s bureaus for GSK and CSL Vifor., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Pharmacological mechanism of Roxadustat in the treatment of renal anemia., Patient Concerns: To investigate the efficacy and safety of combined Roxadustat and erythropoiesis stimulator (ESA) treatment of renal anemia in hemodialysis patients with secondary hyperparathyroidism., Diagnoses: A retrospective analysis was conducted on hemodialysis patients with renal anemia and secondary hyperparathyroidism treated with ESAs alone, who were admitted to our hospital from March 2022 to December 2022., Interventions: The patients were treated with Roxadustat combined with ESAs for 3 months, during which oral iron supplementation was given, and the changes in Hb levels and laboratory-related indicators before and after the combined treatment were analyzed., Outcomes: The results showed that a total of 13 patients received combination therapy, with a significant increase in Hb compared to ESAs alone (t = -3.955, P = .002). The Hb qualification rate was 38.46%, and the ∆Hb response rate was 76.92%. The parathyroid hormone significantly decreased with a statistically significant difference (Z = -2.062b, P = .039). Hemoglobin (RBC), total iron binding capacity, and serum ferritin (male) were significantly increased compared to ESAs alone. Total cholesterol and low-density lipoprotein were significantly lower than ESAs alone. The differences in the changes in the above indicators were statistically significant (P < .05). There was no statistically significant difference in changes in other laboratory-related indicators (P > .05). No adverse reactions were observed during the combined treatment of 13 patients., Lessons Subsections: The combination of Roxadustat and ESAs can effectively improve renal anemia in hemodialysis patients with secondary hyperparathyroidism, as well as improve indicators of hyperparathyroidism and blood lipid levels with high levels of safety. This combined treatment thus provides a new and safe treatment method for these patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The prevalence of anemia in adults with diabetes is of growing importance due to its impact on overall health and the management of diabetes-related complications. This study aimed to determine the prevalence of anemia among adult patients with diabetes at King Abdulaziz University Hospital in Jeddah, Saudi Arabia. A retrospective study was done on 1208 patients with diabetes >18 years who attended the study setting from 2010 to 2022. Data about patients' demographics, body mass index, glycated hemoglobin (HbA1c; %), hemoglobin (Hb), serum ferritin, iron, mean corpuscular Hb, mean corpuscular volume, free thyroxine and triiodothyronine (T3), and serum thyroid-stimulating hormone (TSH) were collected. Of patients, 86.6% had anemia with a prevalence of 30.2%, 47.6%, and 22.2% for mild, moderate, and severe anemias, respectively. The prevalence of anemia was significantly higher among females, those with high serum ferritin, normal serum iron or normal serum T3, lower mean HbA1c level (%), lower serum iron or T3, and higher serum ferritin or TSH. A significant positive correlation was found between Hb level and HbA1c level (%), serum iron, free T3, and body mass index. A significant negative correlation was found between Hb level and mean corpuscular volume, serum ferritin, and serum TSH. Being female, having high serum ferritin, lower mean free T3, and a high TSH were risk factors for anemia. The prevalence of severe anemia was significantly higher among patients with uncontrolled diabetes mellitus. A high prevalence of anemia was found among studied diabetics. Anemia screening should be included in the routine assessment of patients with diabetes. A multidisciplinary approach involving endocrinologists, hematologists, and dietitians is recommended to ensure holistic care and address all aspects of the patient's health. In addition, further research should be supported to better understand the mechanisms linking diabetes and anemia and to establish evidence-based guidelines for managing anemia in diabetics., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients., Patient Concerns: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation., Diagnoses: The child was diagnosed with CH with alpha thalassemia., Interventions: The patient was treated with levothyroxine sodium and anemia correction., Outcomes: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age., Conclusions: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia., Lesson: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

We aimed to compare the clinical efficacy and safety of roxadustat with erythropoiesis-stimulating agents, particularly erythropoietin (EPO), in the treatment of maintenance hemodialysis patients with renal anemia. A prospective cohort study was carried out at the Nephrology Department of the Nantong First People's Hospital and Nantong University Affiliated Hospital from December 2020 to December 2021. We compared hemoglobin (Hb) levels, serum ferritin (SF) levels, and adverse cardiovascular events between the roxadustat and EPO groups at 1, 3, and 6 months into the treatment. A total of 209 patients participated in the study, with 112 in the roxadustat group and 97 in the EPO group. At baseline, no statistically significant differences were observed between the 2 groups in terms of age, gender, weight, dialysis modality and duration, previous EPO dosage, Hb levels, SF levels, transferrin saturation, heart function classification, and blood pressure levels (P > .05). After 1 month, Hb levels in the roxadustat group were significantly higher than those in the EPO group (P < .05). However, no statistically significant differences were found between the 2 groups at 3 and 6 months (P > .05). Additionally, there were no significant differences in SF levels and the occurrence of adverse cardiovascular events between the 2 groups after treatment (P > .05). Roxadustat was superior to EPO in the initial treatment phase, while its cardiovascular safety was comparable to that of EPO., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Anemia represents a well-established risk factor for patients diagnosed with gastric cancer, and is often associated with an unfavorable prognosis. In this context, the timely prediction of distant metastasis risk in patients with anemic gastric cancer assumes paramount importance., Methods: Information of gastric cancer patients complicated with preoperative anemia in the First Affiliated Hospital of Sun Yat-sen University was collected. The cohort from the First Affiliated Hospital of Guangxi Medical University was used as an external validation set. A Nomogram was established based on the risk factors screened by univariate and multivariate logistic regression analyses., Results: A total of 848 gastric cancer patients with preoperative anemia were enrolled. Pyloric obstruction, carcinoma antigen 125, T stage, N stage, tumor size, and preoperative weight loss were independent predictors of distant metastasis in gastric cancer patients with anemia (p < 0.05), based on which a nomogram was constructed. The accuracy, reliability and clinical value of the nomogram were evaluated by concordance index, receiver operating characteristic curve, decision curve analysis, calibration curve and showed good stability and clinical predictive value., Conclusions: Preoperative anemic gastric cancer patients, complicated with pyloric obstruction, elevated CA125, advanced T and N stage, larger tumor size, and preoperative weight loss, should be paid more attention to distant metastasis., (© 2024. The Author(s).)

Introduction: Numerous clinical trials affirm the efficacy and safety of IV iron to treat cancer-related anemia (CRA). Nonetheless, evaluation and treatment of CRA remains suboptimal., Areas Covered: This review summarizes CRA therapy with a focus on iron deficiency and its treatment. The literature search was conducted using the National Library of Medicine (PubMed) database from 2004 to 2024. Topics reviewed include CRA pathophysiology, laboratory diagnosis of iron deficiency, a summary of clinical trial results using IV iron to treat CRA, and safety aspects., Expert Opinion: Despite overwhelming positive efficacy and safety data, IV iron remains underutilized to treat CRA. This is likely due to persistent (unfounded) concerns about IV iron safety and lack of physician awareness of newer clinical trial data. This leads to poor patient quality of life and patient exposure to anemia treatments that have greater safety risks than IV iron. Solutions to this problem include increased educational efforts and considering alternative treatment models in which other providers separately manage CRA. The recent availability of new oral iron therapy products that are effective in treating anemia of inflammation has the potential to dramatically simplify the treatment of CRA.

Objective: Juvenile arthritis caused by loss-of-function LACC1 mutations is characterized by early onset of symmetric and chronic arthritis, associated with an elevation of inflammatory markers. We aimed to describe serum cytokine levels, explore the type I interferon pathway, and evaluate the efficacy of treatment in a patient presenting with polyarthritis and anemia caused by novel compound heterozygous variations in LACC1., Methods: Clinical data of a patient with compound heterozygous variations in LACC1 was collected. Serum cytokine levels and IFN-stimulated cytokine genes were analyzed at diagnosis, at disease flare, and after treatment. Full-length cDNA of LACC1 was checked by RNA analysis. Single-cell RNA sequencing was performed in PBMCs., Results: Two novel variants in the LACC1 gene were identified in a patient presenting with polyarthritis and anemia. LACC1-cDNA was normally expressed in the healthy control, the target production at 1384 bp was not observed in the patient. Compared to nine patient controls with non-systemic juvenile idiopathic arthritis, serum interleukin(IL)-6 level was significantly elevated in the affected patient. The median IFN score for the patient, her mother, and controls were 118, 8, and 4.9, respectively. The combined treatment of JAK inhibitors with prednisone or tocilizumab led to a complete response, including remission of joint symptoms, resolution of anemia, reduced expression of IFN-stimulated cytokine genes, and normalized levels of inflammatory markers, including CRP, ESR, SAA, and serum IL-6., Conclusion: LACC1 may play a crucial role in multiple inflammatory signaling pathways. The combination therapy of JAK inhibitors and tocilizumab may be effective for a subset of refractory patients., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Approximately 7000 total hip arthroplasty (THA) surgeries occur in Ireland each year. A number of preoperative factors have been identified that increase the risk of postoperative blood transfusion after THA, including anaemia. The ability to identify patients at risk may allow preoperative management strategies to reduce blood transfusions. Data from Irish orthopaedic patients is currently lacking., Aim: To investigate if preoperative anaemia and other factors are associated with postoperative blood transfusions in patients who undergo THA., Methods: A retrospective cohort study of all patients who underwent THA in 2019 in SIVUH, Cork, using medical chart review., Results: In total, 350 charts met the inclusion criteria, with 291 charts reviewed. 8.9% of the patients who underwent THA had preoperative anaemia. Among these, 19.2% had a postoperative blood transfusion, compared to 1.5% of patients who were not anaemic preoperatively. The odds of receiving a blood transfusion was 15.5 times greater in the preoperative anaemia group compared to the non-anaemic group. Increasing age and higher ASA scores were associated with preoperative anaemia and postoperative blood transfusions. Length of stay was increased by 2.2 days (p < 0.00016) if blood transfusion was required., Conclusion: Preoperative anaemia was common in an Irish orthopaedic population undergoing THA. Preoperative anaemia predisposes patients to the greatest increased risk of postoperative blood transfusions. The other factors associated with the need for postoperative transfusion were ASA grade 3 or more and age greater than 65 years. Patients who received postoperative blood transfusions had a significantly increased length of hospital stay., (© 2024. The Author(s).)

Purpose: Renal anemia is a common complication of chronic kidney disease. Currently, recombinant human erythropoietin and roxadustat are the main treatments. In China, diabetic kidney disease is the primary cause of chronic kidney disease. However, high-quality evidence on the efficacy of roxadustat in patients with non-dialysis-dependent chronic kidney disease and diabetes mellitus is scarce. This study aimed to assess the clinical effect of roxadustat in such patients., Methods: Patients with non-dialysis-dependent anemia and diabetes mellitus who received roxadustat or recombinant human erythropoietin for ≥ 4 weeks were enrolled. We compared baseline characteristics, including age, gender, hypertension, and hemoglobin level, and then employed a 1:3 ratio propensity score matching. The primary efficacy outcomes were changes in hemoglobin levels. After propensity score matching, 212 patients were analyzed, including the roxadustat (n = 53) and recombinant human erythropoietin (n = 159) groups. Baseline characteristics were comparable, including hemoglobin level, estimated glomerular filtration rate, and glycated hemoglobin A1c (p > 0.05)., Results: After 4, 12, and 24 weeks of treatment, the median hemoglobin levels in the roxadustat group were 97.5 g/L, 104 g/L, and 106.5 g/L, respectively, significantly surpassing the corresponding levels in the recombinant human erythropoietin group at 91 g/L, 94.5 g/L, and 94.5 g/L (p = 0.002, p = 0.025, p = 0.006, respectively). Additionally, subgroup analysis demonstrated better treatment efficacy of roxadustat patients with elevated high-sensitivity C-reactive protein and low albumin levels., Conclusion: In Chinese patients with anemia and diabetes not on dialysis, roxadustat efficiently and rapidly improved and maintained hemoglobin levels unaffected by elevated high-sensitivity C-reactive protein and low albumin levels., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Study Objective: To determine the sex-specific associations between postoperative haemoglobin and mortality or complications reflecting ischaemia or inadequate oxygen supply after major noncardiac surgery., Design: A retrospective cohort study with prospective validation., Setting: A large university hospital health system in China., Patients: Men and women undergoing elective major noncardiac surgery., Interventions and Measurements: The primary exposure was nadir haemoglobin within 48 h after surgery. The outcome of interest was a composite of postoperative mortality or ischaemic events including myocardial injury, acute kidney injury and stroke within hospitalisation., Main Results: The study included 26,049 patients (15,757 men and 10,292 women). Low postoperative haemoglobin was a strong predictor of the composite outcome in both sexes, with the risk progressively increasing as the nadir haemoglobin concentration dropped below 130 g l -1 in men and 120 g l -1 in women (adjusted odds ratio [OR] 1.43, 95% CI 1.37-1.50 in men, and OR 1.45, 95% CI 1.35-1.55 in women, per 10 g l -1 decrease in postoperative nadir haemoglobin). Above these sex-specific thresholds, the change of nadir haemoglobin was no longer associated with odds of the composite outcome in either men or women. There was no significant interaction between patient sex and the association between postoperative haemoglobin and the composite outcome (Pinteraction = 0.673). Validation in an external prospective cohort (n = 2120) with systematic postoperative troponin and creatinine measurement confirmed our findings., Conclusions: Postoperative haemoglobin levels following major noncardiac surgery were nonlinearly associated with ischaemic complications or mortality, without any clinically important interaction with patient sex., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Osteopetrosis encompasses rare inherited metabolic bone disorders with defect in the osteoclast activity. Severe forms of presentation such as malignant infantile osteopetrosis are seen in infants and milder forms in older children. The clinical presentation includes failure to thrive, severe pallor, optic atrophy and hepatosplenomegaly. The disorder is characterised by dense bone on radiography, hence the name marble bone disease. A 10-month-old boy who presented with developmental delay, failure to thrive, nystagmus (which the mother described as wandering eye movements), splenomegaly of 16 cm and hepatomegaly of 8 cm. Investigations demonstrated severe anaemia (5.7 g/dL) and thrombocytopenia (34 x 109/L). Radiological signs which help in the diagnosis include diffuse sclerosis, bone within bone appearance, sandwich vertebrae and Erlenmeyer flask deformity. Plain radiography is an easily available and cost effective tool which can aid in the diagnosis of osteopetrosis.

This study assessed the prevalence of iron overload in infants born to Rh isoimmunized mothers. Infants born to Rh isoimmunized mothers with Indirect Coomb's Test (ICT) titers ≥1:16 were prospectively enrolled and followed until 3 mo. Hemoglobin and serum ferritin were estimated at birth and 3 mo of age. The outcomes were the incidence of iron overload (at birth and 3 mo), anemia, and the need for transfusions in the first 3 mo. Seventy-four infants were enrolled, nearly half receiving intrauterine transfusion (IUT). Sixty (82.2%) had hyperferritinemia at birth. The median (1 st , 3 rd quartile) ferritin levels were 456 (321, 631) μg/L. Infants who received IUTs had significantly higher serum ferritin levels at birth. Fifty-one (76.1%) infants had hyperferritinemia at 3 mo. Over three months of follow-up, 53 (71.6%) infants had anemia, of which 33 (48.5%) required packed red blood cells (PRBC) transfusion. These findings suggest that iron overload is common in these infants in the first 3 mo., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Chronic anemia is an independent risk factor for mortality in patients with heart failure (HF). Restoring physiological hemoglobin (Hb) levels is essential to increase oxygen transport capacity to tissues and improve cell metabolism as well as physical and cardiac performance. Nutritional deficits and iron deficiency are the major causes of chronic anemia, but other etiologies include chronic kidney disease, inflammatory processes, and unexplained anemia. Hormonal therapy, including erythropoietin (EPO) and anabolic treatment in chronic anemia HF patients, may contribute to improving Hb levels and clinical outcomes. Although preliminary studies showed a beneficial effect of EPO therapy on cardiac efficiency and in HF, more recent studies have not confirmed this positive impact of EPO, alluding to its side effect profile. Physical exercise significantly increases Hb levels and the response of anemia to treatment. In malnourished patients and chronic inflammatory processes, low levels of anabolic hormones, such as testosterone and insulin-like growth factor-1, contribute to the development of chronic anemia. This paper aims to review the effect of nutrition, EPO, anabolic hormones, standard HF treatments, and exercise as regulatory mechanisms of chronic anemia and their cardiovascular consequences in patients with HF., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Anemia is one of the most frequent extra-intestinal manifestations of inflammatory bowel disease. Insidious onset, variability of symptoms and lack of standardized screening practices may increase the risk of underestimating its burden in children with IBD. Despite its relevance and peculiarity in everyday clinical practice, this topic is only dealt with in a few documents specifically for the pediatric field. The aim of the current guidelines is therefore to provide pediatric gastroenterologists with a practical update to support the clinical and therapeutic management of children with IBD and anemia. A panel of 19 pediatric gastroenterologists and 1 pediatric hematologist with experience in the field of pediatric IBD was agreed by IBD Working group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) to produce the present article outlining practical clinical approaches to the pediatric patient with IBD and anemia. The levels of evidence and recommendations have been defined for each part of the statement according to the GRADE system., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare with regards to this manuscript., (Copyright © 2024 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Migrant patients share the same diseases as natives, but biological or environmental differences may lead to distinct prevalence and manifestations of certain syndromes. Some common conditions in Primary Care stand out, such as fever, diarrhea, anemia, eosinophilia, and chronic cough, where it is important to have a special consideration. Fever may indicate a serious imported illness, and malaria should always be ruled out. Diarrhea is generally of infectious origin, and in most cases, management is outpatient. Anemia may indicate malnutrition or malabsorption, while eosinophilia may indicate a parasitic infection. Lastly, chronic cough may be a sign of tuberculosis, especially in immigrants from endemic areas. Family medicine holds a privileged position for the comprehensive, culturally sensitive, and person-centered approach to these conditions., (Copyright © 2024 The Authors. Publicado por Elsevier España S.L.U. All rights reserved.)

Objective: To characterize the evaluation and outcomes of children referred to pediatric hematology for normocytic anemia., Study Design: Retrospective cohort study of children aged 0-21 years referred to a tertiary pediatric hematology clinic for normocytic anemia from 2019 through 2021. Normocytic anemia was defined as a low hemoglobin and normal mean corpuscular volume, per the referring laboratory reference range., Results: Two-hundred seventy-one patients (48% female, median age 5.4 years) were included. The most common hematologic diagnoses included iron deficiency (n = 90, 33%), statistical anemia (n = 64, 24%), transient marrow suppression (n = 36, 13%), and transient erythroblastopenia of childhood (TEC, n = 19, 7%). There were 17 (6%) patients in whom anemia was thought to be secondary to a nonhematologic disorder and therefore were referred to another pediatric specialty. Sixteen patients (6%) had anemia which spontaneously resolved without an underlying etiology being identified. Aside from iron deficient patients, 35 (13%) had diagnoses requiring ongoing hematology care including transient erythroblastopenia of childhood, hemolytic anemia, Diamond Blackfan Anemia, and abnormal beta globin traits. Two-hundred fifty-one patients (93%) were discharged from hematology care after a median of 25 days (range 0-2124 days)., Conclusion: Pediatric patients with normocytic anemia have diverse underlying etiologies with iron deficiency being most common. These data support initial management within the primary care setting including assessment of a serum ferritin, iron panel, and reticulocyte count, with only a subset of patients requiring ongoing subspecialty care., Competing Interests: Declaration of Competing Interest Dr Powers discloses past consultancy to Pharmacosmos, LLC, which is unrelated to the content of this manuscript. Ms Kirk discloses advisory board with Sanofi and honoraria from BioMarin and X4 Pharmaceuticals which are unrelated to the content of this manuscript. Ms Equitz has no conflicts to disclose. Baylor College of Medicine, no external funding was secured for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The Kidney Disease Improving Global Outcomes guidelines recommend nephrology referral for patients with chronic kidney disease (CKD) stages 4 to 5, significant proteinuria and persistent microscopic haematuria. However, the recommendations are opinion-based and which patients with CKD benefit more from nephrology referral has not been elucidated., Methods: In this retrospective cohort study, patients referred to our nephrology outpatient clinic from April 2017 to March 2019 were included. We excluded patients considered to have an acute decline in kidney function (annual decline in estimated glomerular filtration rate [eGFR] >10 mL/min/1.73 m 2 ). The slopes of eGFR before and after nephrology referral were estimated and compared by linear mixed effects models. Interaction between time and referral status (before or after referral) was assessed and effect modifications by the presence of diabetes, proteinuria (defined by urine dipstick protein 2+ or more), urine occult blood, hypoalbuminemia (defined by albumin levels less than 3.5 g/dL) and anaemia (defined by haemoglobin levels less than 11.0 g/dL) were evaluated., Results: The eGFR slope significantly improved from -2.05 (-2.39 to -1.72) to -0.96 (-1.36 to -0.56) mL/min/1.73 m 2 /year after nephrology referral (p < .001). The improvement in eGFR slope was more prominent among those with diabetes mellitus, anaemia, and hypoalbuminemia (all p-values for three-way interaction <.001 after adjustment for covariates). Further adjustments for time-dependent haemoglobin levels, the use of erythropoiesis-stimulating agents, iron supplementation, anti-hypertensives and anti-diabetic medications did not change the significance of the interactions., Conclusions: Nephrology referral slows CKD progression, especially among those with hypoalbuminemia, diabetes or anaemia. Patients with hypoalbuminemia, diabetes or anaemia might benefit more from specialized care and lifestyle modifications by nephrologists. The inclusion of anaemia and hypoalbuminemia in nephrology referral criteria should be considered., (© 2024 Asian Pacific Society of Nephrology.)

Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion. Further, transfusion carries many risk factors that must be balanced with benefits. Therefore, transfusion practice in ICU patients has constantly evolved, and we endeavor to present a contemporary review of transfusion practices in this population guided by clinical trials and expert guidelines.

Background: Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia., Methods: Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization., Results: From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 [0.4] to 12.7 [1.1] g/dL; PRINCE: 11.3 [1.0] to 14.0 [1.3] g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 [0.2] to 12.8 [2.6] g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% [3 of 5 patients]; PRINCE: 25.0% [2 of 8] to 87.5% [7 of 8]; PEGASUS: 0 to 72.7% [8 of 11]). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation., Conclusion: Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan., Trial Registration: Trial registration numbers: PADDOCK (NCT02588833), PRINCE (NCT04085601; EudraCT, 2018-004220-11), PEGASUS (NCT03500549)., Competing Interests: JP: reports consultancy and honoraria at Blueprint Medicines, Amgen, F Hoffmann-La Roche, MSD, Bristol Myers Squibb, Alexion Pharmaceuticals, Novartis, Pfizer, Gilead, Boehringer Ingelheim, Swedish Orphan Biovitrum, and Apellis Pharmaceuticals; and honoraria from Swiss Biopharma. ND: has nothing to disclose SO: has nothing to disclose RPdL: has nothing to disclose PS: reports membership on an entity’s Board of Directors or advisory committees with Blueprint Medicines and Swedish Orphan Biovitrum AB; Honoraria, Membership on an entity’s Board of Directors or advisory committees and Speakers Bureau with Alexion and Bristol Myers Squibb; Honoraria and Membership on an entity’s Board of Directors or advisory committees with MSD and Novartis. NS: reports membership of advisory committee with Alexion. MA-A: was an employee at the time of this study and held stock options. EP: is an employee of Swedish Orphan Biovitrum AB. RSMW: has received consulting fees, honoraria, research funding, and speaker’s bureau fees from Alexion and F. Hoffmann-La Roche Ltd.; and research funding and speaker’s bureau fees from Apellis. These affiliations do not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Panse et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients' complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH., Methods: We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People's Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence., Results: Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability., Conclusions: The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Asymptomatic malaria in pregnancy (AMiP) is a daunting public health problem with multifaceted adverse outcomes for mothers, fetuses, newborns and beyond. This study aimed to assess the prevalence and risk factors of AMiP and anaemia in Majang Zone, Gambella, Southwest Ethiopia., Methods: A facility-based cross-sectional study was conducted among 425 pregnant women attending the antenatal care (ANC) clinics of five health facilities in the Majang Zone from November 2022 to February 2023. Sociodemographic, obstetric, and anti-malarial intervention data were collected using an interviewer-administered questionnaire. A capillary blood specimen was collected to diagnose malaria and anaemia as well as determine the blood group. Malaria was diagnosed by rapid diagnostic test (RDT), microscopy, and quantitative polymerase chain reaction (qPCR). Statistical analyses were done by Statistical Package for Social Science (SPSS) version 26.0. The association between dependent and independent variables was assessed by multivariable binary logistic regression, considering P < 0.05 statistically significant. The magnitude of associations was quantified with the adjusted odds ratio (AOR) along with the corresponding 95% confidence interval (CI)., Results: The overall prevalence of AMiP was 15.3% (95% CI 12.1, 18.9). It was 11.3% (95% CI 8.4, 14.7) by RDT, 11.8% (95% CI 8.9, 15.2) by microscopy and 17.6% (95% CI 11.7, 24.9) by qPCR. Plasmodium falciparum, moderate parasitaemia and submicroscopic infection accounted for 55.4% of the AMiP prevalence, 50.8% of the parasite density, and 41.6% of the qPCR-positive AMiP, respectively. Nearly 32.3% of pregnant women with AMiP carried gametocytes. Risk factors of AMiP were: not utilizing insecticide-treated net (ITN) within the previous week (AOR: 9.43 95% CI 1.57, 56.62), having a history of malaria within the previous year (AOR: 2.26 95% CI 1.16, 4.42), lack of indoor residual spraying (IRS) within the previous year (AOR: 3.00 95% CI 1.50, 6.00), and ANC contact below two rounds (AOR: 4.28 95% CI 2.06, 8.87). The prevalence of anaemia was 27.7% (95% CI 23.6, 32.1), and it was higher among AMiP-positives (56.9%) than the negatives (22.5%) (P: 000)., Conclusion: The prevalence of AMiP and anaemia was high, and remained as a critical public health problem in the study area. Focus on the identified risk factors and introduction of more sensitive diagnostic tools should be considered to mitigate AMiP in the study area., (© 2024. The Author(s).)

In low- and middle-income countries, indoor air pollution (IAP) is a serious public health concern, especially for women and children who cook with solid fuels. IAP exposure has been linked to a number of medical conditions, including pneumonia, ischemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lung cancer, and anaemia. Around 500 million women of reproductive age (WRA) suffer from anaemia globally, with an estimated 190 million cases in sub-Saharan Africa (SSA). This study, which is based on prior research, investigates the relationship between IAP exposure and anaemia among WRA in Ghana. A diverse sample of 2,406 WRA living in Ghana were interviewed, of which 58.06% were anaemic and used high-pollutant fuels for cooking. Age, place of residence, region, education level, religion, ethnicity, wealth index, type of drinking water, type of toilet facility, and type of cooking fuels were all found to be significantly linked with anaemic state by bivariate analysis. Type of cooking fuels utilized, age, region of residence, and the type of residence were shown to be significant predictors of anaemia status using sequential binary logit regression models. The results emphasise the critical need for efforts to promote the usage of clean cooking fuel in an attempt to lower anaemia prevalence in Ghana. To reduce dependency on solid fuels for cooking, initiatives should promote the use of cleaner cooking fuels and enhance the socioeconomic status of households. These interventions could have significant public health effects by reducing the burden of anaemia and improving maternal and child health outcomes due to the prevalence of anaemia among WRA. Overall, this study sheds light on the relationship between IAP exposure and anaemia in Ghana and highlights the demand for focused public health initiatives to address this serious health problem., (© 2024. The Author(s).)

Aim: To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС)., Materials and Methods: Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer)., Results: The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n =43) had higher rates of daily proteinuria ( p< 0.001), systolic blood pressure ( p< 0.05), serum levels of interferon γ ( p< 0.001) and hepcidin ( p< 0.001) and lower values of eGFR ( p< 0.05) than patients without anemia (group II; n =36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p< 0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p< 0.05), hepcidin (r=-0.459; p< 0.05) and CRP (r=-0.453; p< 0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p< 0.05) and the mass index of the left ventricular myocardium (r=-0.619; p< 0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p< 0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p< 0.05). The leading value of anemia (beta -0,29; p= 0,04) and depression of the s-Klotho level (beta -0,44; p= 0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron ( n =40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved., Conclusion: Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Traditionally, the treatment of anemia associated with chronic kidney disease (CKD) involves prescribing erythropoiesis-stimulating agents (ESAs) or iron preparations. The effectiveness and safety of ESAs and iron have been established. However, several clinical issues, such as hyporesponsiveness to ESAs or defective iron utilization for erythropoiesis, have been demonstrated. Recently, a new class of therapeutics for renal anemia known as hypoxia-inducible factor (HIF)/proline hydroxylase (PH) inhibitors has been developed. Several studies have reported that HIF-PH inhibitors have unique characteristics compared with those of ESAs. In particular, the use of HIF-PH inhibitors may maintain target Hb concentration in patients treated with a high dose of ESAs without increasing the dose. Furthermore, several recent studies have demonstrated that patients with CKD with defective iron utilization for erythropoiesis had a high risk of cardiovascular events or premature death. HIF-PH inhibitors increase iron transport and absorption from the gastrointestinal tract; thus, they may ameliorate defective iron utilization for erythropoiesis in patients with CKD. Conversely, several clinical problems, such as aggravation of thrombotic and embolic complications, diabetic retinal disease, and cancer, have been noted at the time of HIF-PH inhibitor administration. Recently, several pooled analyses of phase III trials have reported the non-inferiority of HIF-PH inhibitors regarding these clinical concerns compared with ESAs. The advantages and issues of anemia treatment by ESAs, iron preparations, and HIF-PH inhibitors must be fully understood. Moreover, patients with anemia and CKD should be treated by providing a physiological erythropoiesis environment that is similar to that of healthy individuals.