Erythrocytes Research Articles

Anemia Acuity Effect on Transfusion Strategies in Acute Myocardial Infarction

In patients with acute myocardial infarction (MI), limited physiologic adaptation to acute anemia might lead to greater benefit from a liberal red blood cell (RBC) transfusion strategy. Data on such a possible benefit are lacking. To compare acute anemia with chronic anemia and post-MI outcomes and estimate the differential effect of a restrictive RBC transfusion strategy compared with a liberal strategy on post-MI outcomes according to anemia acuity. A prespecified subgroup analysis of the Myocardial Ischemia and Transfusion (MINT) multicenter randomized clinical trial was conducted in 126 hospitals in 6 countries between April 26, 2017, and April 14, 2023, with 30-day follow-up and blinded adjudication of the primary outcome. The analysis included 3144 of 3504 MINT participants (89.7%) with acute MI, a hemoglobin (Hb) level less than 10 g/dL at randomization, and a first Hb measurement available on the day of or the day following hospital admission. The MINT trial randomized participants to a restrictive (Hb <7-8 g/dL) or liberal (Hb <10 g/dL) RBC transfusion strategy. Acute anemia was defined as having a first Hb value greater than 13 g/dL (men) or 12 g/dL (women), or as having a decrease greater than or equal to 2 g/dL between the first Hb measurement and measurement at randomization. Other Hb levels were categorized as chronic anemia. The primary outcome was a composite of death or recurrent MI up to 30 days after randomization. Secondary outcomes were death, recurrent MI, cardiac death, heart failure, pulmonary complications, and major bleeding events. Intention-to-treat analysis was performed. Among 3144 included participants (mean [SD] age, 72.3 [11.6] years; 1715 [54.5%] male; 1307 [41.6%] with type 1 MI), 1078 [34.3%]) had acute anemia. Acute anemia was associated with an increased risk of death or recurrent MI (adjusted risk ratio, 1.25; 95% CI, 1.05-1.48). The effect of a restrictive RBC transfusion strategy compared with a liberal strategy was similar for participants with either acute or chronic anemia for all outcomes. In this secondary analysis of the MINT trial, acute anemia was associated with less favorable post-MI outcomes than chronic anemia but did not modify the effects of the randomized transfusion strategy. In patients with anemia and MI, the acuity of anemia should not influence the choice of transfusion trigger. ClinicalTrials.gov Identifier: NCT02981407.

The hematopoietic activity of EPO is unfavorable to the treatment of bleomycin-induced pulmonary fibrosis in mice

The main function of erythropoietin (EPO) is to promote hematopoiesis and improve anemia. In addition, EPO also has many non-hematopoietic effects such as anti-inflammation, anti-apoptosis and anti-oxidation. To achieve the protective effects, large doses of EPO are required, so the probability of side effects increases. Previous studies have revealed that EPO can improve pulmonary fibrosis in mice, but it has not been clarified whether the hematopoiesis of EPO contributes to amelioration of pulmonary fibrosis and whether EPO improves overall mortality. Our results show that EPO decreases hydroxyproline content, α-sma and col-1 protein levels in mice with bleomycin-induced pulmonary fibrosis. However, compared with the control group, the weight loss and mortality rate of the EPO group were not improved, while the number of red blood cells (RBCs), hemoglobin (Hb), red cell width distribution-coefficient of variation (RDW-CV) and hematocrit (HCT) were significantly higher. Furthermore, we observed massive thrombosis in the lung of EPO treated lung fibrosis mice but not in control mice. Therefore, our results show that in the condition of lung fibrosis, the hematopoietic activity of exogenous EPO is not conducive to its tissue protective effect.

Alloimmunization in Pregnancy: Implications for the Fetus and Neonate.

Blood group or red cell alloimmunization occurs when a pregnant patient has produced antibodies to a blood group antigen possessed by the fetus and not possessed by the pregnant patient. Maternal antibodies are usually produced as an immune response to fetal-maternal bleeding or blood product transfusion. Prevention remains the most important strategy to avoid the formation of maternal antibodies or alloimmunization. Maternal alloimmunization may result in transplacental passage of these antibodies into the fetal circulation and the potential for fetal or neonatal hemolysis and anemia. Red cell alloimmunization can result in significant perinatal morbidity and mortality. Management of alloimmunization in pregnant patients should be protocol-driven. Current strategies for assessment and therapies allow for more thorough and less invasive management with risks to mother and fetus.

Oxygen extraction–guided transfusion strategy in critically ill patients: study protocol for a randomised, open-labelled, controlled trial

IntroductionIn critically ill patients, individualised strategies for red blood cell transfusion (RBCT) are lacking. The objective of this study is to demonstrate the potential advantages of employing an individualised transfusion...

Imetelstat, a novel, first‐in‐class telomerase inhibitor: Mechanism of action, clinical, and translational science

AbstractMost cancers and neoplastic progenitor cells have elevated telomerase activity and preservation of telomeres that promote cellular immortality, making telomerase a rational target for the treatment of cancer. Imetelstat is a first‐in‐class, 13‐mer oligonucleotide that binds with high affinity to the template region of the RNA component of human telomerase and acts as a competitive inhibitor of human telomerase enzymatic activity. Pharmacokinetics, pharmacodynamics, exposure‐response analyses, efficacy, and safety of imetelstat have been evaluated in vitro, in vivo, and clinically in solid tumor and hematologic malignancies, including lower‐risk myelodysplastic syndromes (LR‐MDS) and myeloproliferative neoplasms. Imetelstat was approved in the United States in June 2024 for the treatment of adult patients with LR‐MDS with transfusion‐dependent anemia requiring four or more red blood cell units over 8 weeks who have not responded to or have lost response to or are ineligible for erythropoiesis‐stimulating agents, with a recommended dosing regimen of 7.1 mg/kg administered via 2‐h intravenous infusion every 4 weeks. In the pivotal trial, significantly more patients treated with imetelstat versus placebo achieved ≥8‐week and ≥24‐week red blood cell‐transfusion independence, and imetelstat was associated with a manageable safety profile characterized primarily by short‐lived and manageable neutropenia and thrombocytopenia. This mini‐review summarizes the mechanism of action, pharmacokinetic and pharmacodynamic characteristics, clinical development, and clinical efficacy and safety data of imetelstat.

Preparation and characterization of micellar nanoparticles using crude saponins from five Congolese plant species

Nanoparticles (NPs) have significantly advanced medical applications, including drug delivery, immunotherapy, vaccines, and diagnostics. This versatility is partly due to the potential of tailoring NPs from multiple sources. Notably, saponins, amphiphilic plant metabolites, have shown great promise in NP formulation. This study explored the development of micellar NPs using saponin crude fractions (SCFs) extracted from five Congolese plant species: Millettia laurentii, Penthaclethra eetveldeana, Schwenckia americana, Musa paradisiaca, and Musa sapientum. Plant materials were subjected to histological examination through optical microscopy, while phytochemical analyses by thin-layer chromatography confirmed the presence and predominance of saponins in the SCFs. We used a phthalocyanine-isoniazid hybrid (Pc-INH) as a hydrophobic probe to determine the critical micellar concentrations of SCFs and explore the feasibility of developing cost-effective saponin-based micelles (SBMs). Phytochemical screenings indicated saponins in the extracted SCF and other metabolites like flavonoids, phenolic acids, and anthocyanins. Dynamic light scattering and transmission electron microscopy analyses revealed the formation of nano-sized particles, particularly noting SBMs from P. eetveldeana with notable dimensions (157 nm, PDI of 0.27, and ZP of -4.01 mV) and spherical shape. The micelles from M. laurentii exhibited superior encapsulation efficiency for Pc-INH (55%) compared to control micelles formulated from pure saponin (33%). In vitro tests showed that M. paradisiaca SBMs have the best safety profile for red blood cells, with a 10% hemolysis rate compared to a 150% rate for bulk SCFs. However, there is a significant difference between SCFs and SBMs (p < 0.0001). The release profiles of M. paradisiaca SBMs show a pH-dependent relationship, suggesting potential for stimuli-responsive drug delivery. This work lays the foundation for leveraging plant-derived crude saponins in nanotechnology, emphazising their encapsulation efficiency, controlled release potential, and biocompatibility, paving the way for the cost-effective production of high-value biomedical NPs.

Clinical Burden and Healthcare Resource Utilization Associated With Managing Transfusion-dependent β-Thalassemia in England

PurposePatients with transfusion-dependent β-thalassemia (TDT) have reduced levels of β-globin, leading to ineffective erythropoiesis and iron overload. Patients with TDT depend on regular red blood cell transfusions (RBCTs) and iron chelation therapy for survival and management of disease- and treatment-related clinical complications. This study describes the clinical and economic burden in patients with TDT in England. MethodsThis longitudinal, retrospective study linked the Clinical Practice Research Datalink (CPRD) database with secondary care data from the Hospital Episode Statistics database to identify patients with a diagnosis of β-thalassemia between July 1, 2008, and June 30, 2018. Included patients had a diagnosis of β-thalassemia prior to the index date, ≥8 RBCTs per year for ≥2 consecutive years, and ≥1 year of follow-up data available from the index date. Each eligible patient was exact matched with up to 5 controls in the CPRD. Proportions of deaths and rates of mortality, acute and chronic complications, and healthcare resource utilization (HCRU) were calculated during the follow-up period. FindingsOf 11,359 identified patients with β-thalassemia, 237 patients with TDT met the eligibility criteria and were matched with 1184 controls. The mean age at the index date was approximately 25 years in the patient and control groups. The proportion of deaths (7.17% vs 1.18%; P < 0.05) and mortality rate (1.19 deaths per 100 person-years vs 0.20 deaths per 100 person-years) were higher among patients with TDT compared to controls. Endocrine complications and bone disorders were the most prevalent complications among patients with TDT (58.23%) and included osteoporosis (29.11%), diabetes mellitus (28.27%), and hypopituitarism (28.27%). Patients with TDT had a mean of 13.62 RBCTs per patient per year (PPPY). HCRU was substantially higher among patients with TDT, wherein patients with TDT had higher rates of prescriptions recorded in primary care (24.09 vs 8.61 PPPY), outpatient visits (16.69 vs 1.31 PPPY), and inpatient hospitalizations (17.41 vs 0.24 PPPY) than controls. Inpatient hospitalizations were primarily <1 day, with 16.62 events PPPY lasting <1 day and 0.79 events PPPY lasting ≥1 day. Patients with TDT aged ≥18 years had increased rates of mortality, clinical complications, and HCRU than those aged <18 years. ImplicationsPatients with TDT in England have higher mortality than matched controls, substantial disease-related clinical complications, and substantial HCRU. High mortality and clinical complications highlight the need for additional innovative therapies for TDT.

Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemia

Cold agglutinin disease (CAD) and warm antibody autoimmune hemolytic anemia (wAIHA) are rare autoimmune hemolytic anemias characterized by red blood cell destruction, largely attributable to complement activation resulting in intravascular and extravascular hemolysis. Pegcetacoplan is a subcutaneously administered C3-targeted therapy, which may be suitable for treating CAD and wAIHA. In this open-label phase 2 study, analyses were conducted in two cohorts, one for patients with CAD and the other wAIHA. In each cohort, patients were randomly assigned to receive 270 or 360 mg/day pegcetacoplan for up to 48 weeks. Safety endpoints included the incidence and severity of treatment-emergent adverse events (TEAEs) and adverse events of special interest (AESI). Efficacy endpoints included change from baseline in hemoglobin (Hb), lactate dehydrogenase, absolute reticulocyte count, haptoglobin, indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue scale. Thirteen (100%) and 10 out of 11 (91%) patients with CAD and wAIHA respectively experienced at least 1 TEAE. Ten patients had at least 1 serious adverse event; none were considered related to pegcetacoplan. The only treatment-related AESIs were injection site reactions. Pegcetacoplan increased Hb levels, reduced hemolysis, and increased FACIT-fatigue scale scores in the first weeks; at week 48 the median (interquartile range) change from baseline Hb for the CAD and wAIHA total groups was 2.4 (0.90 to 3.00) and 1.7 g/dL (-1.40 to 2.90), respectively, and improvements in hemolysis and FACIT-fatigue scale scores were maintained. This study demonstrated that pegcetacoplan is generally well tolerated and suggests it can be effective in patients with CAD and wAIHA. Registered at www.clinicaltrials.gov (NCT03226678).

Mortality association with extremity trauma and transferring patients for higher level of care.

Rising healthcare costs and reduced Medicaid reimbursements pose lasting challenges for trauma centers. Various studies have highlighted the adverse effect of these cost-related circumstances on trauma center survival and the need for local hospitals to transfer patients to tertiary and quaternary care centers. Our study seeks to assess the relationship between patient transfer status to a higher-level health center and its association with mortality. A total of 19417 patients were identified, of which 15317 patients presented directly to the higher level health center, and 3830 patients who transferred from 49 different outside hospitals within a 500-mile radius. Data collection was collected from the receiving higher level of care hospital trauma registry. IBM SPSS version 23 was used to analyze the data. A 1:1 propensity-matched analysis based on age, sex, and injury severity score yielded 3566 patients that presented directly to ARMC and 3566 patients who were transferred to ARMC for a higher level of care. Amongst various factors we considered mechanism of injury, response levels, arrival methods, and transfusion of blood products. The univariate analysis of the propensity-matched analysis demonstrated 88% blunt injury in the nontransferred group and 82% in the transferred group (P<0.001). Overall, hospital mortality was 3% in nontransferred patients versus 4% in the transferred group (P<0.001). A multivariate logistic regression demonstrated mortality is more likely in patients with higher injury severity scores [odd ratio (OD) 2.351 (1.029-1.082), P<0.001] and lack of packed red blood cell (pRBC) transfusions received within first 4h [OD 6.852 (3.525-13.318), P=0.001]. The transfer of trauma patients with extremity injuries to level 1 trauma centers has significant implications on patient outcomes. In our retrospective observational cohort study, the authors noted increased mortality among patients with higher injury severity scores, penetrating injuries, pRBC administration within the first 4h of hospitalization, and among patient transfers.

Clinical Burden and Health Care Resource Utilization Associated With Managing Sickle Cell Disease With Recurrent Vaso-occlusive Crises in England

PurposeSickle cell disease (SCD) is an inherited red blood cell disease caused by a mutation in the gene encoding the β-subunit of adult hemoglobin that leads to hemolysis, anemia, vaso-occlusive crises (VOCs), morbidity, and mortality. This study provides a real-world assessment of the clinical burden and health care resource utilization (HCRU) associated with SCD with recurrent VOCs in England. MethodsThis retrospective study linked primary care records from the Clinical Practice Research Datalink database with secondary care records from the Hospital Episode Statistics database to identify patients with SCD with recurrent VOCs between July 1, 2008, and June 30, 2018. A VOC was defined as SCD with crisis, acute chest syndrome, or priapism. Eligible patients had SCD, ≥2 VOCs/year in any 2 consecutive years after a diagnosis of SCD, and ≥1 year of follow-up data from the index date. Patients were exact matched with 5 controls from the general population in the databases. Demographics were assessed at index. Mortality, clinical complications, and HCRU were summarized during follow-up. FindingsAfter applying eligibility criteria, 1117 patients with SCD with recurrent VOCs and 5585 controls were included in the study. Mean age at index was 25 years in both groups. The proportion of deaths (3.67% vs 0.68%; P < 0.001) and mortality rate (0.78 deaths per 100 person-years vs 0.16 deaths per 100 person-years) were substantially higher in patients with SCD with recurrent VOCs versus matched controls. Mean (standard deviation [SD]) age of death in patients with SCD with recurrent VOCs who died during the follow-up period was 40.17 (14.09) years. The mean (SD) rate of VOCs for patients with SCD with recurrent VOCs was 5.84 (12.50) per patient per year (PPPY) during follow-up. Compared with matched controls, patients with SCD with recurrent VOCs had substantially higher mean [SD] rates PPPY of inpatient hospitalizations (7.59 [14.50] vs 0.32 [2.71]), prescriptions (31.06 [60.62] vs 7.58 [27.77]), and outpatient visits (9.60 [10.69] vs 1.78 [4.18]). Older patients and those with increased numbers of VOCs had increased mortality, frequency of clinical complications, and HCRU. ImplicationsDespite currently available care, patients with SCD with recurrent VOCs in England have increased mortality, substantial clinical complications, and significant HCRU driven by VOCs and hospitalizations. Elevated mortality and clinical complications in patients with SCD with recurrent VOCs highlight the need for novel therapies in this space.

Label-Free Non-Contact Vascular Imaging using Photon Absorption Remote Sensing.

Functional vascular imaging is a critical method for early detection and prevention of disease. Established non-contact vascular imaging techniques capture predominantly structural information. In this study, a novel non-contact label-free in vivo Photon Absorption Remote Sensing (PARS) microscope is developed for structural and functional vascular imaging. The presented in vivo PARS microscope captures the endogenous absorption of green (532nm) light to form a complete picture of vasculature and surrounding tissues. Imaging system repeatability is enhanced through robust transient absorption signal extraction, and state-of-the-art real-time alignment methods. Detailed imaging of vascular structure is demonstrated through in vivo microscopy of two established animal models: mouse ear and chicken embryo. Preliminary functional contrast is realized through video rate imaging of red blood cell dynamics in the capillary networks of chicken embryos. The presented in vivo PARS microscope successfully captures detailed structural and functional vascular contrast. This innovative non-contact label-free imaging technique holds promise as a tool for preventative medical care, as functional change often precedes structural change.

Synthesis, characterisation of ZnO@PDA@Ag nanocomposite: Mechanistic interaction with BSA, photodegradation activity & in vitro cytotoxicity assay on H1299 lung cancer cell line

Despite advancements in diagnosis and therapeutic, cancer retains to be a greatest cause of fatality and economic damage to the world. Metallic nanoparticles have grabbed attention particularly in the field of medicine attributed to their noteworthy biological and catalytic properties, offering significant progress. The work aimed to create a novel biocompatible ‘Silver doped Polydopamine coated Zinc-Oxide nanocomposite’ and investigate its efficacy in treating H1299 lung cancer cells as well as water remediation. In this study, a ‘ZnO@PDA@Ag’ Nanocomposite was synthesised using co-precipitation method and was further characterised using DLS, FESEM-EDX, P-XRD, XPS, TEM and FT-IR techniques. The mechanistic interaction with blood protein, suggested strong binding interactions and notable structural changes in BSA upon exposure to the nanocomposite. The photocatalytic properties evaluated against the Rhodamine B Dye under UV–Visible light irradiation demonstrated a photodegradation of~49.77 % within 120 min for 60 μg/mL of the used nanocomposite. Herein, we present an evaluation of anticancer bioactivity of ZnO@PDA@Ag nanoparticles using MTT assay against the H1299 lung cancer cell line and its IC50 was estimated to be (42.42 ± 4) μg/mL. The cytotoxicity was enhanced through immobilization of Silver (Ag) metal on ZnO@PDA. Moreover, the hemolysis experiment was also conducted to demonstrate the biocompatibility of nanoparticle to human red blood cells. As a result, the successfully created biocompatible nanomaterial may be useful as an efficient drug-delivery system against cancer cells.

Evaluation of HRR (Hemoglobin/Red Blood Cell Distribution Width Ratio) and RAR (Red Blood Cell Distribution Width/Albumin Ratio) in Myocarditis Patients: Associations with Various Clinical Parameters.

This study investigates the prognostic value of the Hemoglobin/Red Blood Cell Distribution Width Ratio (HRR) and the Red Blood Cell Distribution Width/Albumin Ratio (RAR) in patients with myocarditis. We aimed to evaluate how these novel biomarkers correlate with clinical parameters, disease severity, and outcomes. A retrospective analysis was conducted on 301 patients diagnosed with myocarditis between January 2020 and March 2024. Inclusion criteria were adults with confirmed myocarditis based on clinical, ECG and echocardiographic evaluations. Exclusion criteria included incomplete records and prior immunosuppressive therapy. We assessed various blood parameters, including HRR and RAR, and analyzed their associations with clinical outcomes, hospital stay duration, and complications. The study found that HRR and RAR were significantly associated with several clinical outcomes in myocarditis patients. Higher HRR values correlated with improved outcomes, while higher RAR values were linked to worse outcomes. HRR was associated with pericardial effusion, inotropic support, and other parameters, while RAR was correlated with similar factors, including recent gastroenteritis. Patients with longer hospital stays exhibited higher inflammation markers and lower ejection fractions, underscoring the severity of their condition. HRR and RAR are promising biomarkers for assessing disease severity and prognosis in myocarditis. They provide additional prognostic information beyond traditional markers such as troponin and CRP, potentially guiding more personalized treatment strategies.

Aflatoxin B1-associated oxidative stress along with toxicopathological and immunological alterations is efficiently counteracted by dietary supplementation of distillery yeast sludge in broilers.

Aflatoxin B1 (AFB1) is among the most potent genotoxic and carcinogenic mycotoxins and is a major source of distress for the growing poultry sector. On the other hand, distillery yeast sludge or distillery sludge (DS) is a byproduct of molasses-based industries. It is often treated as a waste despite containing abundant nutrients particularly protein, basic amino acids, and vitamins along with other macro and micronutrients. This study was designed to investigate the oxidative stress and immunological alterations induced by AFB1 and their amelioration by dietary supplementation with DS. For this purpose, 360 newly hatched broiler chicks were randomly divided into twelve groups (30 birds each) and fed different combinations of AFB1 (100, 200, or 600µg/kg) and DS (5 or 10g/kg) for 42days. The parameters under consideration were body weight, feed conversion ratio (FCR), relative organ weights, histopathological examination of different visceral organs, total antioxidant capacity, antibody response to intravenous injection of sheep red blood cells, in situ lymphoproliferative response to phytohemagglutinin-P, and phagocytic potential through a carbon clearance assay system. The results of this study established that DS supplementation ameliorated AFB1-associated oxidative stress and ameliorated toxicopathological and immunological anomalies in groups given AFB1 at 100µg/kg and 200µg/kg; however, little to no relief was observed in birds fed AFB1 at 600µg/kg. The determination of the actual ratio of the AFB1 to the DS for substantiating the ameliorating effects requires further investigation.

Innovative fluorescent ratiometric probe from Oolong tea dreg for highly sensitive bilirubin detection

Bilirubin, a crucial component in heme degradation, is formed during the breakdown of red blood cells in the liver and spleen. Elevated bilirubin levels are closely associated with jaundice and serve as markers for various blood and liver-related disorders. Detection of BR has been approached through various methods with fluorescent methods gaining prominence due to their exceptional sensitivity, rapid response, and precision. Among the fluorescence methods, carbon dots have emerged as versatile optical probes, known for their unique optical properties, low toxicity, and ease of synthesis. However, carbon dots typically exhibit a single emission peak, limiting accuracy due to vulnerability to external interferences. To overcome this limitation, probes featuring multiple independent emission signals are preferred. Chlorophyll, abundant in nature and sourced from biomass, is recognized for its safe and fluorescent properties, making it a secure choice for fluorescence-based sensing. This study introduces an innovative approach utilizing Oolong tea dreg as a source of chlorophyll for creating a fluorescent probe to detect bilirubin. Chlorophyll was partially converted into carbon dots using a combination of extraction and hydrothermal techniques, producing a ratiometric probe with two emission signals. The fluorescence of the probe was quenched in the presence of the bilirubin through the inner filter effect. The proposed probe exhibited outstanding selectivity and a low limit of detection (0.8 µM) for bilirubin. Furthermore, the probe demonstrated satisfactory recovery rates when tested with artificial urine and human urine samples.

Marked microcytosis and increased transferrin saturation: Think about variants in SLC11A2 (DMT1)

Congenital microcytic anemias are rare diseases associated with decreased hemoglobin synthesis and red blood cells of low corpuscular volume. DMT1/NRAMP2 is a highly conserved divalent cation transporter encoded by the SLC11A2 gene, expressed at the membrane of various cells. It ensures ferrous iron absorption from the apical membrane of enterocytes, iron recovery from urine by renal tubules, and acidified endosome uptake after transferrin internalization. Pathogenic DMT1 variants have been described in 10 individuals to date, associated with recessive hypochromic anemia and iron overload. Herein, we report a new variant of SLC11A2 (c.469A>G, p.Ile157Val) compound with known p.Arg416Cys associated with a frankly microcytic anemia and increased transferrin saturation. The clinical picture observed in the patient was exceptionally mild, extending the field of the DMT1 phenotypes to borderline anemias.

Variations in antenatal management and outcomes in haemolytic disease of the fetus and newborn: an international, retrospective, observational cohort study

Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies. In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available. 2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres. We found considerable variation in antenatal management and outcomes in haemolytic disease of the fetus and newborn between sites in different countries. Our study shows the capacity of the field to gather valuable data on a rare disease and to optimise care. None.

Association Between Red Blood Cell Distribution Width in Late Pregnancy and the Incidence of Adverse Perinatal Outcomes: A Retrospective Cohort Study

This study aimed to quantify adverse perinatal outcomes (APO), including small/large for gestational age (SGA/LGA) and preterm birth (PTB), in pregnant women with abnormal red cell distribution width (RDW) and explore the related mechanisms. This study included 11,659 pregnant women who delivered in a specialized hospital. At the time of admission, the lipid profiles and whole blood cell counts were assessed, and APO was analyzed. Women with high RDW (>18.5% [the 97.5th percentile]) in late pregnancy had a higher risk of LGA compared with those with low RDW (<12.3% [the 2.5th percentile]), whereas women with low RDW had a higher risk of SGA and PTB, compared with those with high RDW. A 1% increase in RDW was associated with an increased risk of LGA and a decreased risk of SGA and PTB. Consistent associations were observed in sensitivity analysis among pregnant women of non-advanced age, non-obesity, non-pregnancy complications, and non-PTB (for SGA/LGA only). Increased RDW was significantly associated with increased triglycerides and decreased high-density lipoprotein cholesterol (HDL-C). Triglycerides and HDL-C significantly mediated 10.63 and 15.8% of RDW-associated LGA, 9.51% and 9.40 of RDW-associated SGA, and 8.44 and -8.25% of RDW-associated PTB, respectively. Abnormal RDW was associated with an increased risk of APO, and the RDW-associated APO risk could be partially mediated by triglycerides and HDL-C, suggesting that RDW may be a promising APO predictor.

Role of Charlson comorbidity index in predicting intensive care unit readmission in patients with aortic aneurysm.

The purpose of this study was to investigate the value of the Charlson comorbidity index (CCI) in predicting intensive care unit (ICU) readmission in aortic aneurysm (AA) patients. Patient information came from the Medical Information Mart for Intensive Care- IV (MIMIC-IV) database. The relationship between CCI and ICU readmission was analyzed by restricted cubic spline, generalized linear regression, trend analysis, and hierarchical analysis. The clinical value of CCI in predicting ICU readmission was analyzed by receiver operating characteristic curve, decision curve analysis, XGBoost regression, and random forest regression. A total of 523 patients with AA were enrolled in the study. Patients with AA who were readmitted to the ICU had higher width of red blood cell distribution width (RDW) and higher CCI. CCI had better performance and clinical net benefit for predicting ICU readmission than RDW. An independent nonlinear relationship was found between CCI and ICU readmission. The trend analysis suggested that the risk of ICU readmission increased with higher CCI scores. The hierarchical analysis showed that their association was mainly found in surgery requirement populations regardless of AA types. Further, CCI was found to have better clinical value in predicting ICU readmission of thoracic aortic aneurysm (TAA) patients undergoing surgery. Age, renal disease, chronic lung disease, and dementia were important components of CCI in predicting ICU readmission of TAA patients undergoing surgery. CCI was independently associated with the ICU readmission of AA patients in a positive relationship and had more favorable prediction performance in TAA patients who underwent surgery.

Folic Acid Before and During Pregnancy

Folate is a key nutrient required to maintain optimal health, especially when planning a family or during pregnancy. The functionality of folate centres on the production of healthy red blood cells, important for the transportation of oxygen around the body. It supports development of the foetal nervous system specifically neural tube growth, with evidence showing that taking folic acid supplements before and during pregnancy reduces the chance of the baby developing spina bifida and other conditions affecting the spine and neural tube.1 Folate is essential for DNA replication, and may protect against miscarriage, premature birth and low birth weight, with beneficial effects in the prevention of structural anomalies, congenital heart disease and oral clefts.2