OBJECTIVE: This first-in-human trial aimed to investigate the pharmacokinetics and pharmacodynamics characteristics and safety and tolerability of single ascending doses of subcutaneous polyethylene glycol-erythropoietin (PEG-EPO) in healthy subjects.
METHODS: In this phase I, randomized, double-blind, placebo-controlled, dose-escalating trial, subjects were sequentially enrolled into 7 cohorts with 12 subjects in each cohort and randomized in a 5:1 ratio to receive a single dose of 0.2, 0.4, 0.8, 1.6, 2.4, 3.6, or 4.8 µg/kg PEG-EPO or matching placebo. Safety and tolerability including dose-limiting toxicities (DLTs) were assessed. Pharmacokinetics parameters, including Cmax, AUC0-inf, Tmax, and t1/2, and pharmacodynamics parameters, including reticulocyte count and hemoglobin content, were evaluated.
RESULTS: Eighty-four subjects (median age 30.4 years and 77.4% male) were enrolled. No subjects developed DLTs. Any grade treatment-related adverse events occurred in 66.7% of the subjects, but most (92.9%) were mild. No serious adverse events and no death occurred. Forty percent of the subjects receiving PEG-EPO had iron decreased, 27.1% reported ferritin decreased, 25.7% showed unsaturated iron binding capacity increased, and 17.1% had neutrophil count decreased. Cmax exhibited a dose-disproportionate rise from a geometric mean of 525 pg/mL with 0.2 µg/kg PEG-EPO to 23196 pg/mL with 4.8 µg/kg PEG-EPO. The mean t1/2 ranged between 82.4 ± 21.3 h with 0.4 µg/kg PEG-EPO and 160.6 ± 65.7 h with 1.6 µg/kg PEG-EPO. AUC0-inf displayed a largely dose-proportional rise from 226264.5 pg*h/mL with 0.2 µg/kg PEG-EPO to 5206434.0 pg*h/mL with 4.8 µg/kg PEG-EPO. The absolute reticulocyte count increased with escalating doses of PEG-EPO, with the mean maximal change from baseline between 3.2 ± 1.5*10^10/L (Q1,Q3 1.8-3.6*10^10/L) with PEG-EPO 0.2 µg/kg and 9.3 ± 4.0*10^10/L (Q1,Q3 6.2-13.5*10^10/L) with 3.6 µg/kg PEG-EPO. The mean maximal change from baseline in the mean hemoglobin content ranged between 5.9 ± 4.4 g/L (Q1,Q3 3.5,7.0) with 0.2 µg/kg PEG-EPO and 15.4 ± 8.7 g/L (Q1,Q3 10.5,20.0) with 2.4 µg/kg PEG-EPO.
CONCLUSIONS: This trial demonstrated that PEG-EPO was safe and tolerable in healthy subjects. The subcutaneous route of administration allows outpatient treatment and the pharmacokinetics characteristics of PEG-EPO support less frequent dosing regimens and effective treatment for chronic kidney disease patients with anemia.
BACKGROUND: clinicaltrials.gov identifier: NCT03657238.

UNASSIGNED: Anemia occurs in majority of patients with chronic kidney disease despite adequate dialysis and iron replete status. This study was done to evaluate the effects of lactoferrin with or without iron supplementation for the treatment of anemia in patients with chronic kidney disease (CKD).
UNASSIGNED: In this prospective, observational, single-center, single-arm pilot study, adult patients aged >18 years, having stage 5 CKD (estimated glomerular filtration rate [eGFR] <15 ml/min/1.73 m2), and who had anemia (hemoglobin [Hb] <10 g/dl; transferrin saturation [Tsat] >20%) were included. Patients were treated with 100 mg of oral lactoferrin twice a day for one month with or without iron supplementation. Patients had been on stable erythropoietin doses for ≥1 month prior to inclusion in the study. We report on the improvement in Hb levels and effect on inflammatory markers from baseline at four weeks.
UNASSIGNED: A total of 46 CKD patients having anemia were included. Patients had a mean age of 39.3 years, and a majority were men (69.6%). Improvement in the mean (SD) Hb level (g/dl) was observed from baseline (8.18 [1.19]) to Week 2 (8.54 [1.57]), which attained significance at Week 4 (8.96 [1.93]; P < 0.001; mean difference: -0.76; 95% confidence interval [CI]: -1.291 to - 0.2383). The improvement in Hb was higher in women than in men (P = 0.48) and in patients receiving lactoferrin with iron supplementation than in those receiving lactoferrin alone (P = 0.14). There was a non-significant decrease in the erythrocyte sedimentation rate (P = 0.14) and a non-significant increase in C-reactive protein (P = 0.54) level.
UNASSIGNED: Oral lactoferrin therapy was effective in improving hemoglobin levels in patients with advanced CKD and anemia. The effects of lactoferrin therapy on inflammatory markers remain uncertain.

UNASSIGNED: The aim of the study was to evaluate the effects of tofogliflozin, a selective sodium-glucose cotransporter 2 inhibitor, on circulating levels of hepatic enzymes, uric acid and hemoglobin levels in patients with type 2 diabetes mellitus (T2DM).
UNASSIGNED: We evaluated longitudinal changes in circulating aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, and hemoglobin levels in tofogliflozin (n = 169) and conventional treatment groups (n = 170) using data obtained from the UTOPIA trial, a randomized prospective study conducted to evaluate the efficacy of tofogliflozin in preventing atherosclerosis.
UNASSIGNED: Within 104 weeks, tofogliflozin treatment, but not conventional treatment, significantly reduced AST, ALT, and γ-GTP levels. This reduction was significantly greater in the tofogliflozin group than in the conventional group. Stratified analysis showed that, in patients with obesity (defined as body mass index (BMI) ≥ 25.0 kg/m2), significant differences were observed in AST, ALT, and γ-GTP changes from baseline to 104 weeks between treatment groups. However, in patients without obesity, there were no significant differences in AST and γ-GTP changes from baseline to 104 weeks between treatment groups. Multivariable regression analysis showed that changes in BMI and HbA1c levels were independently associated with changes in AST, ALT, and γ-GTP levels. The reduction of uric acid and the increase of hemoglobin from baseline to 104 weeks were significantly greater in the tofogliflozin group than in the conventional group.
UNASSIGNED: The beneficial effects of tofogliflozin on circulating levels of hepatic enzymes, uric acid, and Hb lasted for 2 years in patients with T2DM.
UNASSIGNED: UMIN000017607 (https://www.umin.ac.jp/icdr/index.html).
UNASSIGNED: The online version contains supplementary material available at 10.1007/s13340-024-00693-x.

UNASSIGNED: Hypertension and anemia are major health problems globally. However, data regarding the association between hypertension and hemoglobin/anemia among adults are few and controversial. Therefore, the current study aimed to investigate the associations between hemoglobin/anemia and hypertension among Sudanese adults.
UNASSIGNED: A community-based cross-sectional study was conducted in Northern Sudan from September to December 2022. The participants\' sociodemographic characteristics were assessed using a questionnaire. Standardized procedures measured participants\' weight, height, body mass index (BMI), hemoglobin, and hypertension. Multivariate regression analysis was performed to determine the association between anemia and hypertension.
UNASSIGNED: Three hundred eighty-four adults were enrolled; 195 (50.8%) and 189 (49.2%) were males and females, respectively. The median interquartile age of the enrolled adults of age, BMI, and hemoglobin level was 45.0 (33.0‒55.8) years, 26.6 (22.6‒30.6) kg/m2, and 13.4 (12.4‒14.4) g/dl, respectively. Of 384 adults, 216 (56.3%) had hypertension, and 148 (38.5%) were newly diagnosed hypertensive. Eighty-six adults (22.4%) had anemia. In univariate analysis, while increasing age, being female, being unmarried, having a positive family history of hypertension, and increasing BMI were positively associated with hypertension, anemia was inversely associated with hypertension. Education, occupation, cigarette smoking, and alcohol consumption were not associated with hypertension. In multivariate analysis, age (adjusted odd ratio [AOR] = 1.05, 95% confidence interval [CI] = 1.03‒1.07), BMI (AOR= 1.07, 95% CI = 1.03‒1.12) were inversely associated with hypertension, being female (AOR = 2.92, 95% CI = 1.43‒5.94), positive family history of hypertension (AOR= 1.73, 95% CI = 1.09‒2.75), and hemoglobin level (AOR= 1.34, 95% CI = 1.12‒1.61) were associated with hypertension. Anemia (AOR = 0.58, 95% CI = 0.34‒0.99) was inversely associated with hypertension.
UNASSIGNED: Both anemia and hypertension are major public health problems in Northern Sudan. Anemia is associated with hypertension. Further research is needed to explore the complex association between hemoglobin/anemia and hypertension.

Introduction Tranexamic acid (TXA) administration perioperatively has demonstrated efficacy in reducing postoperative drops in hemoglobin levels and the need for transfusions among patients with peritrochanteric hip fractures. This study aims to perform a retrospective analysis to assess the impact on hemoglobin levels by comparing patients with fragility hip fractures who received TXA in the ED, in addition to the standard perioperative TXA dose, with those who did not receive TXA in the ED. Methods This study retrospectively reviewed 64 patient records from May 2020 to May 2021 at a Level II trauma center that were classified into two groups: patients who received one gram (g) of TXA in the ED, within five hours of injury (new protocol), or patients who received no TXA in the ED (old protocol). The primary outcomes of the study were hemoglobin and adverse events. An independent t-test was performed on continuous variables. A chi-square test was used to analyze noncontinuous variables. Statistical Product and Service Solutions (SPSS, version 25; IBM SPSS Statistics for Windows, Armonk, NY) was used for analysis. Statistical significance was set at a p value < 0.05. Results We measured the difference between hemoglobin on the day of surgery or day zero and on arrival in the ED, which was not statistically significant between the two protocols (p value = 0.322). The difference between hemoglobin levels on postoperative day one and on arrival in the ED was also not statistically significant (p = 0.339). Adverse events were lower in the new protocol but not statistically significant between the two protocols (p = 0.178). Conclusion Our study showed improved outcomes in postoperative hemoglobin with early administration of TXA in the ED. This is demonstrated by continuous higher postoperative hemoglobin in the new protocol group without an increase in adverse events. While the data did not achieve statistical significance, we believe there is clinical benefit in the early administration of TXA in the ED, a finding that continues to be explored and supported in the literature.

Gastrointestinal bleeding is the most common cause of iron deficiency in adult men and menstrual blood loss is the leading cause of iron insufficiency in women, anemia due to iron deficiency is mostly caused by blood loss. Ferric carboxymaltose (FCM) is a contemporary parenteral iron formulation that may be used therapeutically to treat anemia caused by an iron deficiency [iron-deficiency anemia (IDA)]. The main goal of the trial was to evaluate FCM\'s safety and efficacy in treating IDA. The Department of Hematology, Rajshahi Medical College Hospital, Rajshahi, Bangladesh participated in this quasi-experimental research, which comprised adult patients with IDA. Participants were given an intravenous (IV) infusion of 500 mg of FCM, diluted in 100 mL of 0.9% normal saline, throughout a 30-minute period after their participation. The second dosage of FCM was administered after a 7-day period of the first dose. The comparison of the outcomes [hemoglobin (Hb) level, serum ferritin level, and other hematological parameters] between the baseline and day 14 postintervention was done using a paired t-test. Compared to baseline, patients\' Hb levels rose considerably (p = 0.001) after FCM. Aside from serum ferritin level, additional hematological parameters that sharply increased were red blood cells (RBCs) count, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width - coefficient of variation (RDW-CV), and iron indicators. The experiment recorded mild adverse effects such as fever, headaches, and gastrointestinal issues including vomiting, diarrhea, and constipation, but no significant adverse events. In summary, IDA may be effectively treated with FCM, a safe and secure IV medication that has no major negative effects.
UNASSIGNED: Miah MMZ, Pramanik MEA, Rafi A, et al. Iron-deficiency Anemia Treatment with Ferric Carboxymaltose: A Real-world Quasi-experimental Study from Bangladesh. Euroasian J Hepato-Gastroenterol 2024;14(1):12-15.

UNASSIGNED: Microcytic anemia due to iron deficiency is the most common type of anemia in children in Israel and many parts of the world, and has been shown to have negative consequences for the cognitive performance. We aimed to examine the association between microcytic anemia at age 9-18 months and ADHD during childhood.
UNASSIGNED: This case-control study included healthy children aged 6-18 years at data collection (April 2020), insured by Clalit-Health-Services, and aged 9-18 months between June 2004 and December 2013, when a blood-count was performed. The study group included children diagnosed with ADHD based on the medical documentation of at least two consecutive stimulant prescriptions. A control group without any stimulant prescriptions was matched in a ratio of 1-3:1, by year of birth, sex and cultural background. Any microcytic anemia was defined as Hb < 10.5 g/dl and MCV 60-75 fl. Moderate microcytic anemia as Hb 7-9.9 g/dl. We performed a conditional-logistic-regression analysis, adjusted by socioeconomic status (SES) and year of birth. Sensitivity analysis examined this association stratified by sex, cultural background, SES and age at data collection quintiles.
UNASSIGNED: Any microcytic anemia prevalence was lower in the ADHD group (n = 19,467) as compared to the controls (n = 39,004) (3.4 % and 4.0 %, respectively), adjusted-OR = 0.86 (95%CI: 0.78, 0.98). The prevalence of moderate microcytic anemia was similar (0.9 % vs. 1.0 %). Lower any microcytic anemia prevalence in the ADHD group was found in boys, secular-traditional Jews, and in the 4th quintile of age (12.1-13.5 years).
UNASSIGNED: We found a small inverse association between microcytic anemia at 9-18-months and ADHD during childhood, thus rejecting our hypothesis that microcytic anemia at infancy is associated with a higher prevalence of ADHD. Further studies are warranted, to examine the effects of ID and brain iron concentration on the development of ADHD in childhood.

BACKGROUND: Leaflet thrombosis (LT) is a multifaceted and underexplored condition that can manifest following transcatheter aortic valve implantation (TAVI). The objective of this study was to formulate a prediction model based on laboratory assessments and clinical parameters, providing additional guidance and insight into this relatively unexplored aspect of post-TAVI complications.
METHODS: The present study was an observational prospective hypothesis-generating study, including 101 patients who underwent TAVI and a screening for LT (the primary endpoint) by multidetector computed tomography (MDCT). All images were acquired on a third-generation dual-source CT system. Levels of von Willebrand factor (vWF) activity, hemoglobin (Hb), and lactate dehydrogenase (LDH) were measured among other parameters. A predictive score utilizing binary logistic regression, Kaplan-Meier time-to-event analysis, and receiver operating characteristics (ROC) analysis was established.
RESULTS: LT (11 subclinical and 2 clinical) was detected in 13 of 101 patients (13%) after a median time to screening by MDCT of 105 days (IQR, 98-129 days). Elevated levels of vWF activity (> 188%) pre-TAVI, decreased Hb values (< 11.9 g/dL), as well as increased levels of LDH (> 312 U/L) post-TAVI and absence of oral anticoagulation (OAC) were found in patients with subsequent LT formation as compared to patients without LT. The established EFFORT score ranged from - 1 to 3 points, with an increased probability for LT development in patients with ≥ 2 points (85.7% of LT cases) vs < 2 points (14.3% of LT cases; p < 0.001). Achieving an EFFORT score of ≥ 2 points was found to be significantly associated with a 10.8 times higher likelihood of developing an LT (p = 0.001). The EFFORT score has an excellent c-statistic (area under the curve (AUC) = 0.89; 95% CI 0.74-1.00; p = 0.001) and a high negative predictive value (98%).
CONCLUSIONS: An EFFORT score might be a helpful tool to predict LT development and could be used in risk assessment, if validated in confirmatory studies. Therefore, the score has the potential to guide the stratification of individuals for the planning of subsequent MDCT screenings.

BACKGROUND: Iron deficiency anemia (IDA) is considered one of the most common medical disorders observed during pregnancy. In low- and middle-income countries (LMICs), anemia and micronutrients deficiencies among pregnant women are associated with low consumption of animal products, monotonous starchy-diets, and seasonal consumption of vegetables and fruits.
METHODS: A cross-sectional study was conducted with 198 pregnant mothers aged between 19-45 years who visited the antenatal care clinics in Northern Jordan to document the prevalence of IDA and to describe the associations between dietary diversity, diet quality scores and oral iron supplementation with the pregnant women iron status. Participants were stratified into three groups by gestational age (n = 66 women per group). Gestational age, blood parameters, minimum dietary diversity score (MDD-W), and prime diet quality score for healthy (PDQSHF) and unhealthy foods (PDQSUF) were assessed using 24- hour dietary recall.
RESULTS: Prevalence of mild to moderate anemia was 27.8% among pregnant women. Third-trimester pregnant women were most affected. 52.5% have depleted iron stores (ferritin < 15 ng/ml), of them 30.8% have iron deficiency, and 21.7% have IDA. The (M ± SD) of the MDD-W, PDQSHF, and PDQSUF were 4.8 ± 1.6, 12.8 ± 3.9, and 7.2 ± 2.8 respectively. 52.5% achieved the MDD-W, 68% consumed < 4 servings/week of healthy food groups, and 50% consumed > 4 servings/week of unhealthy food groups. Mothers with higher MDD-W and PDQS had higher Hb and serum concentrations. Those taking iron supplements had significantly (p = 0.001) higher means of Hb, serum ferritin, and gestational weight gain. Significant differences were also found between PDQSHF, PDQSUF and the first and third trimester.
CONCLUSIONS: Mild to moderate IDA is prevalent among pregnant mothers, especially in the third trimester. However, the prevalence of IDA among Jordanian pregnant women is lower than the global average. A high-quality, diverse diet, combined with oral iron supplementation and food fortification with iron, will help improve iron status, prevent anemia, and reduce its prevalence.

BACKGROUND: The hemoglobin value to trigger RBC transfusion for patients receiving venovenous extracorporeal membrane oxygenation (ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin level, but recent studies suggest that more RBC transfusions are associated with increased adverse outcomes.
OBJECTIVE: Is implementation of different institutional RBC transfusion thresholds for patients receiving venovenous ECMO associated with changes in RBC use and patient outcomes?
METHODS: This single-center retrospective study of patients receiving venovenous ECMO used segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC use. Associations with secondary outcomes, including in-hospital survival, also were assessed.
RESULTS: The study included 229 patients: 91 in the no threshold cohort, 48 in the hemoglobin < 8 g/dL cohort, and 90 in the hemoglobin < 7 g/dL cohort. Despite a decrease in number of RBC units transfused per day of ECMO support after implementation of different thresholds (mean ± SD: 0.6 ± 1.0 in the no threshold cohort, 0.3 ± 0.8 in the hemoglobin < 8 g/dL cohort, and 0.3 ± 1.1 in the hemoglobin < 7 g/dL cohort; P < .001), segmented regression showed no association between implementation of transfusion thresholds and changes in trends in number of RBC units per day of ECMO. We observed an increased hazard of death in the no threshold cohort compared with the hemoglobin < 8 g/dL cohort (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.12-3.88) and in the hemoglobin < 7 g/dL cohort compared with the hemoglobin < 8 g/dL cohort (aHR, 1.93; 95% CI, 1.02-3.62). No difference was found in the hazard of death between the no threshold and hemoglobin < 7 g/dL cohorts (aHR, 1.08; 95% CI, 0.69-1.69).
CONCLUSIONS: We observed a decrease in number of RBC units per day of ECMO over time, but changes were not associated temporally with implementation of transfusion thresholds. A transfusion threshold of hemoglobin < 8 g/dL was associated with a lower hazard of death, but these findings are limited by study methodology. Further research is needed to investigate optimal RBC transfusion practices for patients supported with venovenous ECMO.