Hematocrit drift and outcomes in surgical patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: There is a paucity of conclusive evidence regarding the impact of downward drift in hematocrit levels among patients who have undergone surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH). This study endeavors to explore the potential association between hematocrit drift and mortality in this specific patient population. METHODS: A cohort study was conducted, encompassing adult patients diagnosed with aSAH at a university hospital. The primary endpoint was follow-up mortality. Propensity score matching was employed to align patients based on their baseline characteristics. Discrimination capacity across various models was assessed and compared using net reclassification improvement (NRI). RESULTS: Among the 671 patients with aSAH in the study period, 118 patients (17.6%) experienced an in-hospital hematocrit drift of more than 25%. Following adjustment with multivariate regression analysis, patients with elevated hematocrit drift demonstrated significantly increased odds of mortality (aOR: 2.12, 95% CI: 1.14 to 3.97; P = 0.019). Matching analysis yielded similar results (aOR: 2.07, 95% CI: 1.05 to 4.10; P = 0.036). The inclusion of hematocrit drift significantly improved the NRI (P < 0.0001) for mortality prediction. When in-hospital hematocrit drift was served as a continuous variable, each 10% increase in hematocrit drift corresponded to an adjusted odds ratio of 1.31 (95% CI 1.08-1.61; P = 0.008) for mortality. CONCLUSIONS: In conclusion, the findings from this comprehensive cohort study indicate that a downward hematocrit drift exceeding 25% independently predicts mortality in surgical patients with aSAH. These findings underscore the significance of monitoring hematocrit and managing anemia in this patient population.

Impact of systematic variations in hematocrit and platelet count on thrombelastometry tissue factor activated assay parameters.

BACKGROUND: Thromboelastogram testing is increasingly being used to manage patients with massive bleeding. An earlier study found that the test results were influenced by the hematocrit (Hct) and platelet (PLT) concentrations. This study sought to determine if these factors confounded the results of a different manufacturer's thromboelastography testing. METHODS: Using freshly collected whole blood from volunteers and stored red blood cells (RBC) and plasma, the whole blood was manipulated to achieve different Hct values and PLT concentrations. Each reconstituted whole blood sample was tested in triplicate on the ROTEM Delta device and the ExTEM results were recorded. RESULTS: Many of the ExTEM results varied according to the Hct and PLT concentration. In particular, the ExTEM clot formation time (CFT) was abnormally long when the Hct was 45% and the PLT concentration was ≤75 × 109/L, normalizing only when the PLT count was ≥100 × 109/L. CFT samples with Hct 25% and 35% were also abnormal with low PLT concentrations but normalized at lower PLT concentrations compared to the Hct 45% samples. The ExTEM angle also demonstrated abnormal results when the Hct was 45% and the PLT concentration was ≤50 × 109/L. The ExTEM A10 and maximum clot firmness (MCF) tests tended to also be abnormal when the Hct was between 25% and 45% and the platelet concentrations were below 75 × 109/L. CONCLUSION: While thromboelastogram testing is gaining popularity for managing bleeding patients, clinicians should be aware of these confounding factors when making transfusion decisions based on their results.

Redefining hyperviscosity in acute leukemia: Potential implications for red cell transfusions in the microvasculature.

Hyperleukocytosis is an emergency of acute leukemia leading to blood hyperviscosity, potentially resulting in life-threatening microvascular obstruction, or leukostasis. Due to the high number of red cells in the circulation, hematocrit/hemoglobin levels (Hct/Hgb) are major drivers of blood viscosity, but how Hct/Hgb mediates hyperviscosity in acute leukemia remains unknown. In vivo hemorheological studies are difficult to conduct and interpret due to issues related to visualizing and manipulating the microvasculature. To that end, a multi-vessel microfluidic device recapitulating the size-scale and geometry of the microvasculature was designed to investigate how Hct/Hgb interacts with acute leukemia to induce "in vitro" leukostasis. Using patient samples and cell lines, the degree of leukostasis was different among leukemia immunophenotypes with respect to white blood cell (WBC) count and Hct/Hgb. Among lymphoid immunophenotypes, severe anemia is protective against in vitro leukostasis and Hct/Hgb thresholds became apparent above which in vitro leukostasis significantly increased, to a greater extent with B-cell acute lymphoblastic leukemia (ALL) versus T-cell ALL. In vitro leukostasis in acute myeloid leukemia was primarily driven by WBC with little interaction with Hct/Hgb. This sets the stage for prospective clinical studies assessing how red cell transfusion may affect leukostasis risk in immunophenotypically different acute leukemia patients.

Predictive value of red blood cell distribution width and hematocrit for short-term outcomes and prognosis in colorectal cancer patients undergoing radical surgery.

BACKGROUND: Previous studies have reported that low hematocrit levels indicate poor survival in patients with ovarian cancer and cervical cancer, the prognostic value of hematocrit for colorectal cancer (CRC) patients has not been determined. The prognostic value of red blood cell distribution width (RDW) for CRC patients was controversial. AIM: To investigate the impact of RDW and hematocrit on the short-term outcomes and long-term prognosis of CRC patients who underwent radical surgery. METHODS: Patients who were diagnosed with CRC and underwent radical CRC resection between January 2011 and January 2020 at a single clinical center were included. The short-term outcomes, overall survival (OS) and disease-free survival (DFS) were compared among the different groups. Cox analysis was also conducted to identify independent risk factors for OS and DFS. RESULTS: There were 4258 CRC patients who underwent radical surgery included in our study. A total of 1573 patients were in the lower RDW group and 2685 patients were in the higher RDW group. There were 2166 and 2092 patients in the higher hematocrit group and lower hematocrit group, respectively. Patients in the higher RDW group had more intraoperative blood loss (P < 0.01) and more overall complications (P < 0.01) than did those in the lower RDW group. Similarly, patients in the lower hematocrit group had more intraoperative blood loss (P = 0.012), longer hospital stay (P = 0.016) and overall complications (P < 0.01) than did those in the higher hematocrit group. The higher RDW group had a worse OS and DFS than did the lower RDW group for tumor node metastasis (TNM) stage I (OS, P < 0.05; DFS, P = 0.001) and stage II (OS, P = 0.004; DFS, P = 0.01) than the lower RDW group; the lower hematocrit group had worse OS and DFS for TNM stage II (OS, P < 0.05; DFS, P = 0.001) and stage III (OS, P = 0.001; DFS, P = 0.001) than did the higher hematocrit group. Preoperative hematocrit was an independent risk factor for OS [P = 0.017, hazard ratio (HR) = 1.256, 95% confidence interval (CI): 1.041-1.515] and DFS (P = 0.035, HR = 1.194, 95%CI: 1.013-1.408). CONCLUSION: A higher preoperative RDW and lower hematocrit were associated with more postoperative complications. However, only hematocrit was an independent risk factor for OS and DFS in CRC patients who underwent radical surgery, while RDW was not.

Photoperiod manipulation improves growth performance, haematological indices and economic returns of Indian butter catfish, Ompok bimaculatus (Bloch, 1794).

Photoperiod manipulation is emerging as an effective approach for regulating physiological functions in fish. This study aimed to assess the impact of photoperiod on the growth performance, haematological responses, and economic returns of the endangered and highly valued Indian butter catfish, Ompok bimaculatus. Fish with an average body weight of 28.60 ± 4.78 g were randomly placed in six FRP tanks, each measuring 120 × 45 × 60 cm3. Each tank contained 20 fish exposed to a light intensity of 1500 lx under different photoperiods [24:0 light: dark (L: D), 15 L: 9D, 12 L: 12D, 9 L: 15D, 0 L: 24D and a natural photoperiod (control)], and fed at a daily rate of 2% of their body weight twice daily for 60 days. The fish in the 15 L: 9D photoperiod exhibited the highest final weight (g), percentage weight gain, specific growth rate (SGR) and survival rate, while the lowest was displayed in 24 L: 0D photoperiod group. The feed conversion ratio (FCR) was at its lowest in the catfish subjected to the 15 L: 9D photoperiod. Regarding haematological parameters, the 15 L: 9D photoperiod group showed higher total erythrocyte count, total leukocyte count, haemoglobin levels, and haematocrit values compared to the other groups. Conversely, the 0 L: 24D group, which experienced prolonged darkness, exhibited the lowest values in these parameters. Moreover, the 24 L: 0D, 9 L: 15D, and 0 L: 24D groups displayed a lower mean corpuscular volume (MCV) but higher mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) when compared to the control group. The economic analysis revealed that O. bimaculatus reared in a moderate photoperiod (15 L: 9D) displayed better growth, feed utilization, and overall health. This finding suggests that adopting a 15 L: 9D photoperiod can lead to enhanced production and improved economic returns for farmers culturing this high-value catfish in the future.

Effect of fermented Cassava sievate and tiger nut shaft on growth performance, blood profile and immunological parameters in male rabbits.

This study examined the effects of using mushroom mycelium to ferment tigernut and cassava pulp on the growth performance, haematology and immunology of rabbits. Seventy-five New Zealand Bulk grower rabbits were randomly distributed to four treatment groups and a control group in a completely randomized approach. The treatment groups were fed with formulated experimental diets containing one of fermented tigernut drink by-product (FT), fermented cassava sievate (FC), unfermented tigernut drink by-product (UT), or unfermented cassava sievate (UC). The control group was fed a basal diet with no additives. The proximate composition of the fermented feed was analyzed. The weight gain of the animals was, 834.5, 633, 790, 510, and 706 g for control, FT, FC, UT, and UC respectively. The packed cell volume (PCV) for animals in the control group, FT, and FC are 34.33, 37.26, and 32.29% respectively. The red blood cell (RBC) of the FT was favourably improved (5.53 × 1012/L) compared to those of UT (2.28 × 1012/L), while there was a reduction in the red blood cell count of FC group (1.02 × 1012/L). Conclusively, the inclusion of fermented tiger nut drink by-product in rabbit feed improved the PCV and RBC of the rabbits' understudy but did not affect their growth performance.

Affordable Method for Hematocrit Determination in Murine Models.

Hematocrit (Hct) is a powerful tool often used in a clinical setting for the diagnosis of blood conditions such as anemia. It is also used in the research field as a hematological parameter in both human and mouse models. Measuring Hct, however, involves the use of expensive standardized equipment (such as a CritSpin™ Microhematocrit Centrifuge). Here, we describe a novel, simple, and affordable method to determine the Hct in untreated wild-type (WT) mice and phenylhydrazine (PHZ)-induced anemic mice with reasonable accuracy, using a benchtop centrifuge commonly available in laboratories. Hct of murine samples processed with a benchtop centrifuge, when compared to the standardized method CritSpin™, showed comparable results. This approach for determining Hct of murine can prove useful to research laboratories that cannot afford specialized equipment for Hct studies. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Affordable Method for Hematocrit Determination in Murine Models Basic Protocol 2: Murine Sample Validation Support Protocol: Phenylhydrazine-induced anemia in wild-type (WT) mice.

Laboratory Changes During Gender-Affirming Hormone Therapy in Transgender Adolescents.

OBJECTIVES: Guidelines for monitoring of medications frequently used in the gender-affirming care of transgender and gender-diverse (TGD) adolescents are based on studies in adults or other medical conditions. In this study, we aimed to investigate commonly screened laboratory measurements in TGD adolescents receiving gender-affirming hormone therapy (GAHT). METHODS: TGD adolescents were recruited from 4 study sites in the United States before beginning GAHT. Hemoglobin, hematocrit, hemoglobin A1c, alanine transaminase, aspartate aminotransferase, prolactin, and potassium were abstracted from the medical record at baseline and at 6, 12, and 24 months after starting GAHT. RESULTS: Two-hundred and ninety-three participants (68% designated female at birth) with no previous history of gonadotropin-releasing hormone analog use were included in the analysis. Hemoglobin and hematocrit decreased in adolescents prescribed estradiol (-1.4 mg/dL and -3.6%, respectively) and increased in adolescents prescribed testosterone (+1.0 mg/dL and +3.9%) by 6 months after GAHT initiation. Thirteen (6.5%) participants prescribed testosterone had hematocrit > 50% during GAHT. There were no differences in hemoglobin A1c, alanine transaminase, or aspartate aminotransferase. There was a small increase in prolactin after 6 months of estradiol therapy in transfeminine adolescents. Hyperkalemia in transfeminine adolescents taking spironolactone was infrequent and transient if present. CONCLUSIONS: Abnormal laboratory results are rare in TGD adolescents prescribed GAHT and, if present, occur within 6 months of GAHT initiation. Future guidelines may not require routine screening of these laboratory parameters beyond 6 months of GAHT in otherwise healthy TGD adolescents.

Using the daily rate of rise in hemoglobin S to manage RBC depletion/exchange treatment in sickle cell disease.

BACKGROUND: Red blood cell exchange is often used prophylactically in patients with sickle cell disease, with the goal to maintain hemoglobin S (HbS) below a target threshold level. We reviewed whether the daily "rate of rise" (RoR) in HbS that occurs between procedures can be used for patient management. For some patients not achieving their HbS goals despite efficient exchanges, the post-procedure hematocrit (Hct) target is increased to potentially suppress HbS production. This case series explores the utility of this approach, other clinical uses of the daily RoR in HbS, and the factors that influence it. STUDY DESIGN AND METHODS: A total of 660 procedures from 24 patients undergoing prophylactic RBC depletion/exchange procedures were included. Laboratory values and clinical parameters were collected and used to calculate the daily RoR in HbS. Factors such as Hct or medications that might influence the RoR in HbS were evaluated. RESULTS: The RoR in HbS varied widely between patients but remained relatively stable within individuals. Surprisingly, this value was not significantly influenced by changes in post-procedure Hct or concurrent hydroxyurea use. A patient's average RoR in HbS effectively predicted the pre-procedure HbS at the following visit (R2 = 0.65). DISCUSSION: The RoR in HbS is a relatively consistent parameter for individual patients that is unaffected by medication use or procedural Hct targets and may be useful in determining intervals between procedures.

Dried blood spot sampling of testosterone microdosing in healthy females.

Capillary dried blood spot (DBS) analysis coupled with multi-analyte steroid liquid chromatography mass spectrometry (LCMS) is attractive for field studies, home-based self-sampling as well as clinical trials by eliminating costly and laborious sample processing involving venipuncture and frozen storage/shipping while providing multiple steroid measurements from a single small sample. We investigated steroid measurements in DBS samples stored for four years at room temperature prior to analysis compared with the original venipuncture serum samples. Healthy women (n=12) provided paired DBS and blood samples over two weeks run-in before seven days treatment with daily transdermal T gel (12.5 mg) and after the end of treatment on days 0, 1, 2, 4, 7 and 14. Compliance with treatment and sampling was high and no adverse effects were reported. Testosterone (T), androstenedione (A4), 17 hydroxyprogesterone (17OHP) and progesterone (P4) were measured in extracted DBS samples as whole blood concentrations with and without adjustment for hematocrit. Using the same LCMS methods, DBS T and A4 measurements had high correlation with minimal bias from prior serum measurements with DBS T displaying the same pattern as serum, with or without hematocrit adjustment. However, serial whole blood measurements of T without hematocrit adjustment provided the best fitting model compared with serum, urine, or hematocrit-adjusted whole blood T measurements. These finding facilitate and simplify DBS methodology for wider field and home-based self-sampling studies of reproductive steroids indicating the need for hematocrit adjustment may be superfluous.

Immune-mediated hemolytic anemia and pure red cell aplasia in a Jack Russell Terrier during treatment for hypoadrenocorticism.

An 11-year-old neutered male Jack Russell Terrier was presented to Yuki Animal Hospital for regenerative anemia during the treatment of hypoadrenocorticism. A blood smear examination showed spherocytes, polychromatic erythrocytes, and erythrocyte ghosts. The direct agglutination test was positive at 37°C. The dog was then diagnosed with immune-mediated hemolytic anemia (IMHA). Although prednisolone and mycophenolate mofetil were administered, the hematocrit and reticulocyte count decreased, and nonregenerative anemia developed. A bone marrow examination was performed to diagnose the cause of the nonregenerative anemia. Histologic and cytologic bone marrow examination revealed a normocellular to hypercellular medulla with severe erythroid hypoplasia. No proliferation of lymphocytes or lymphoblast-appearing cells was observed. This dog was diagnosed with pure red cell aplasia (PRCA). Despite treatment with immunosuppressive agents, the patient died of thrombosis. Although these associations were unclear, this is the first report of PRCA diagnosis following IMHA and while treating hypoadrenocorticism.

Analyzing and modeling massive transfusion strategies and the role of fibrinogen-How much is the patient actually receiving?

BACKGROUND: Hemorrhage is a leading cause of preventable death in trauma, cardiac surgery, liver transplant, and childbirth. While emphasis on protocolization and ratio of blood product transfusion improves ability to treat hemorrhage rapidly, tools to facilitate understanding of the overall content of a specific transfusion strategy are lacking. Medical modeling can provide insights into where deficits in treatment could arise and key areas for clinical study. By using a transfusion model to gain insight into the aggregate content of massive transfusion protocols (MTPs), clinicians can optimize protocols and create opportunities for future studies of precision transfusion medicine in hemorrhage treatment. METHODS: The transfusion model describes the individual round and aggregate content provided by four rounds of MTP, illustrating that the total content of blood elements and coagulation factor changes over time, independent of the patient's condition. The configurable model calculates the aggregate hematocrit, platelet concentration, percent volume plasma, total grams and concentration of citrate, percent volume anticoagulant and additive solution, and concentration of clotting factors: fibrinogen, factor XIII, factor VIII, and von Willebrand factor, provided by the MTP strategy. RESULTS: Transfusion strategies based on a 1:1:1 or whole blood foundation provide between 13.7 and 17.2 L of blood products over four rounds. Content of strategies varies widely across all measurements based on base strategy and addition of concentrated sources of fibrinogen and other key clotting factors. DISCUSSION: Differences observed between modeled transfusion strategies provide key insights into potential opportunities to provide patients with precision transfusion strategy.

Dietary iron or inulin supplementation alters iron status, growth performance, intramuscular fat and meat quality in finisher pigs.

Forty LW × L pigs (20 boars and 20 gilts) (51.1 ± 0.41 kg) were allocated to a 2 × 2 × 2 factorial design with the respective factors being supplemental organic iron (Fe, 0 and 500 mg/kg), inulin (In, 0 and 50 g/kg) and sex (boars and gilts). After 5 weeks the animals were transported to an abattoir before slaughter and collection of samples. Serum iron was increased by supplemental Fe (28.4 v. 30.9 µmol/L, P = 0.05), although there was an interaction (P = 0.03) such that pigs fed diets with In had lower serum Fe concentrations than those without In (26.8 v. 32.3 µmol/L). Boars had lower (P < 0.01) haemoglobin (116 vs 125), haematocrit (36.7 v. 39.7%) and erythrocyte (6.6 v. 7.1 × 106/mL) concentrations than gilts. Dietary In increased liveweight gain (795 v. 869 g/d, P < 0.02) and carcass weight (62.9 v. 65.2 kg, P < 0.02). Dietary Fe or In supplementation did not improve muscle Longissimus thoracis et lumborum (LTL) total Fe concentration (P > 0.05). Muscle non-heme Fe concentration was higher in Fe-supplemented pigs (P < 0.04) and gilts (P < 0.05) than their counterparts. Muscle heme Fe concentration was greater (3.04 vs 2.51, P < 0.05) in boars than in gilts. The LTL marbling score was greater (P < 0.01) for In-supplemented pigs, and the response was more notable when Fe and In were fed together. These data show that dietary supplementation of Fe increased serum Fe and muscle non-heme Fe concentrations. Supplementation of In at 5% in the diet of finisher pigs improved liveweight gain and the marbling score of pork.

A homogenized two-phase computational framework for meso- and macroscale blood flow simulations.

BACKGROUND AND OBJECTIVE: Owing to the complexity of physics linked with blood flow and its associated phenomena, appropriate modeling of the multi-constituent rheology of blood is of primary importance. To this effect, various kinds of computational fluid dynamic models have been developed, each with merits and limitations. However, when additional physics like thrombosis and embolization is included within the framework of these models, computationally efficient scalable translation becomes very difficult. Therefore, this paper presents a homogenized two-phase blood flow framework with similar characteristics to a single fluid model but retains the flow resolution of a classical two-fluid model. The presented framework is validated against four different sets of experiments. METHODS: The two-phase model of blood presented here is based on the classical diffusion-flux framework. Diffusion flux models are known to be less computationally expensive than two-fluid multiphase models since the numerical implementation resembles single-phase flow models. Diffusion flux models typically use empirical slip velocity correlations to resolve the motion between phases. However, such correlations do not exist for blood. Therefore, a modified slip velocity equation is proposed, derived rigorously from the two-fluid governing equations. An additional drag law for red blood cells (RBCs) as a function of volume fraction is evaluated using a previously published cell-resolved solver. A new hematocrit-dependent expression for lift force on RBCs is proposed. The final governing equations are discretized and solved using the open-source software OpenFOAM. RESULTS: The framework is validated against four sets of experiments: (i) flow through a rectangular microchannel to validate RBC velocity profiles against experimental measurements and compare computed hematocrit distributions against previously reported simulation results (ii) flow through a sudden expansion microchannel for comparing experimentally obtained contours of hematocrit distributions and normalized cell-free region length obtained at different flowrates and inlet hematocrits, (iii) flow through two hyperbolic channels to evaluate model predictions of cell-free layer thickness, and (iv) flow through a microchannel that mimics crevices of a left ventricular assist device to predict hematocrit distributions observed experimentally. The simulation results exhibit good agreement with the results of all four experiments. CONCLUSION: The computational framework presented in this paper has the advantage of resolving the multiscale physics of blood flow while still leveraging numerical techniques used for solving single-phase flows. Therefore, it becomes an excellent candidate for addressing more complicated problems related to blood flow, such as modeling mechanical entrapment of RBCs within blood clots, predicting thrombus composition, and visualizing clot embolization.

Altered haematological parameters in children with malaria infection, a systematic review and meta-analysis.

OBJECTIVE: This study aimed to illustrate the effect of malaria infection on red blood cell parameters in children and evaluate the diagnostic relevance of haematological parameters in predicting malaria. METHODS: The studies were identified through databases like PubMed, Google Scholar, and Scopus to retrieve related articles. Fourteen studies were selected by literature search based on inclusion and exclusion criteria, and a meta-analysis on different red blood cell parameters was performed. RESULTS: Haematocrit, haemoglobin concentration, and RBC count show statistically significant findings with p values of (<0.00001), (p<0.00001) and (p=0.0004), respectively. Other parameters like MCV, MCH, and MCHC show statistically non-significant results with p values of 0.21, 0.36, and 0.63, respectively. CONCLUSION: Considering the above findings, the combination of haemoglobin concentration, haematocrit, and RBC counts could be used as reliable parameters to predict the presence of infection and included in the diagnostic strategy for malaria in children.

Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.

Hypoxia-inducible factor pathway genes are linked to adaptation in both human and nonhuman highland species. EPAS1, a notable target of hypoxia adaptation, is associated with relatively lower hemoglobin concentration in Tibetans. We provide evidence for an association between an adaptive EPAS1 variant (rs570553380) and the same phenotype of relatively low hematocrit in Andean highlanders. This Andean-specific missense variant is present at a modest frequency in Andeans and absent in other human populations and vertebrate species except the coelacanth. CRISPR-base-edited human cells with this variant exhibit shifts in hypoxia-regulated gene expression, while metabolomic analyses reveal both genotype and phenotype associations and validation in a lowland population. Although this genocopy of relatively lower hematocrit in Andean highlanders parallels well-replicated findings in Tibetans, it likely involves distinct pathway responses based on a protein-coding versus noncoding variants, respectively. These findings illuminate how unique variants at EPAS1 contribute to the same phenotype in Tibetans and a subset of Andean highlanders despite distinct evolutionary trajectories.

Selective sodium-glucose cotransporter-2 inhibitors in the improvement of hemoglobin and hematocrit in patients with type 2 diabetes mellitus: a network meta-analysis.

Objective: To compare the effects of different selective sodium-glucose cotransporter-2 inhibitors (SGLT2i) on hemoglobin and hematocrit in patients with type 2 diabetes mellitus (T2DM) with a network meta-analysis (NMA). Methods: Randomized controlled trials (RCTs) on SGLT2i for patients with T2DM were searched in PubMed, Embase, Cochrane Library, and Web of Science from inception of these databases to July 1, 2023. The risk of bias (RoB) tool was used to evaluate the quality of the included studies, and R software was adopted for data analysis. Results: Twenty-two articles were included, involving a total of 14,001 T2DM patients. SGLT2i included empagliflozin, dapagliflozin, and canagliflozin. The NMA results showed that compared with placebo, canagliflozin 100mg, canagliflozin 300mg, dapagliflozin 10mg, dapagliflozin 2mg, dapagliflozin 50mg, dapagliflozin 5mg, empagliflozin 25mg, and dapagliflozin 20mg increased hematocrit in patients with T2DM, while canagliflozin 100mg, canagliflozin 200mg, canagliflozin 300mg increased hemoglobin in patients with T2DM. In addition, the NMA results indicated that canagliflozin 100mg had the best effect on the improvement of hematocrit, and canagliflozin 200mg had the best effect on the improvement of hemoglobin. Conclusion: Based on the existing studies, we concluded that SGLT2i could increase hematocrit and hemoglobin levels in patients with T2DM, and canagliflozin 100mg had the best effect on the improvement of hematocrit, while canagliflozin 200mg had the best effect on the improvement of hemoglobin. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#loginpage, identifier PROSPERO (CRD42023477103).

Intraoperative Anemia Mediates Sex Disparity in Operative Mortality After Coronary Artery Bypass Grafting.

BACKGROUND: Women undergoing coronary artery bypass grafting (CABG) have higher operative mortality than men. OBJECTIVES: The purpose of this study was to evaluate the relationship between intraoperative anemia (nadir intraoperative hematocrit), CABG operative mortality, and sex. METHODS: This was a cohort study of 1,434,225 isolated primary CABG patients (344,357 women) from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (2011-2022). The primary outcome was operative mortality. The attributable risk (AR) (the risk-adjusted strength of the association of female sex with CABG outcomes) for the primary outcome was calculated. Causal mediation analysis derived the total effect of female sex on operative mortality risk and the proportion of that effect mediated by intraoperative anemia. RESULTS: Women had lower median nadir intraoperative hematocrit (22.0% [Q1-Q3: 20.0%-25.0%] vs 27.0% [Q1-Q3: 24.0%-30.0%], standardized mean difference 97.0%) than men. Women had higher operative mortality than men (2.8% vs 1.7%; P < 0.001; adjusted OR: 1.36; 95% CI: 1.30-1.41). The AR of female sex for operative mortality was 1.21 (95% CI: 1.17-1.24). After adjusting for nadir intraoperative hematocrit, AR was reduced by 43% (1.12; 95% CI: 1.09-1.16). Intraoperative anemia mediated 38.5% of the increased mortality risk associated with female sex (95% CI: 32.3%-44.7%). Spline regression showed a stronger association between operative mortality and nadir intraoperative hematocrit at hematocrit values <22.0% (P < 0.001). CONCLUSIONS: The association of female sex with increased CABG operative mortality is mediated to a large extent by intraoperative anemia. Avoiding nadir intraoperative hematocrit values below 22.0% may reduce sex differences in CABG operative mortality.

Rusfertide, a Hepcidin Mimetic, for Control of Erythrocytosis in Polycythemia Vera.

BACKGROUND: Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown. METHODS: In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms). RESULTS: Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common. CONCLUSIONS: In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).

Neonatal polycythemia: prevalence, risk factors and predictors of severity.

BACKGROUND: Polycythemia is a disorder with several causes and risk factors. The clinical presentation is variable, ranging from asymptomatic newborns to cases with severe physiological changes. The aim of this study was to assess the prevalence, risk factors and predictors of severity of polycythemia in a Portuguese level III Neonatal Intensive Care Unit (NICU). METHODS: Case-control study of all term newborns with the diagnosis of polycythemia admitted to the NICU of the São João Universitary Hospital Center, Porto, Portugal, from January 1, 1999 to December 31, 2019; and who met one of the following inclusion criteria were eligible for the study: 1) Hct>65% or Hb>22 g/dL; and 2) Hb≥21 g/dL with clinical manifestations of polycythemia. RESULTS: A total of 53 newborns fulfilled the inclusion criteria and were included in the study, corresponding to a prevalence of 0.57%. Birth outside the hospital was the only risk factor with statistical significance. Of 53 cases, 51 (96.23%) had symptomatic polycythemia. The most frequent symptoms were: hyperbilirubinemia (69.81%), hypoglycemia (52.83%), thrombocytopenia (50.94%), cardiorespiratory (33.96%), and neurological symptoms (33.96%). Of the 53 newborns evaluated, 41 (77.36%) needed treatment. The only risk factors that influenced the hematocrit value were maternal diabetes and fetal growth restriction. CONCLUSIONS: The best way to improve the prognosis of polycythemia is to identify the risk factors present throughout pregnancy and make an early diagnosis and treatment. Out-of-hospital births should be avoided. The diagnosis should not be excluded, even if hemoglobin and hematocrit are within normal limits.