Nitrosyl iron complexes are remarkably multifactorial pharmacological agents. These compounds have been proven to be particularly effective in treating cardiovascular and oncological diseases. We evaluated and compared the antioxidant activity of tetranitrosyl iron complexes (TNICs) with thiosulfate ligands and dinitrosyl iron complexes (DNICs) with glutathione (DNIC-GS) or phosphate (DNIC-PO4-) ligands in hemoglobin-containing systems. The studied effects included the production of free radical intermediates during hemoglobin (Hb) oxidation by tert-butyl hydroperoxide, oxidative modification of Hb, and antioxidant properties of nitrosyl iron complexes. Measuring luminol chemiluminescence revealed that the antioxidant effect of TNICs was higher compared to DNIC-PO4-. DNIC-GS either did not exhibit antioxidant activity or exerted prooxidant effects at certain concentrations, which might have resulted from thiyl radical formation. TNICs and DNIC-PO4- efficiently protected the Hb heme group from decomposition by organic hydroperoxides. DNIC-GS did not exert any protective effects on the heme group; however, it abolished oxoferrylHb generation. TNICs inhibited the formation of Hb multimeric forms more efficiently than DNICs. Thus, TNICs had more pronounced antioxidant activity than DNICs in Hb-containing systems.

Plastic particles, particularly micro- and nanoparticles, are emerging pollutants due to the ever-growing amount of plastics produced across a wide variety of sectors. When plastic particles enter a biological medium, they become surrounded by a corona, giving them their biological identity and determining their interactions in the living environment and their biological effects. Here, we studied the interactions of microstructured plastics with hemoglobin (Hb). Virgin polyethylene microparticles (PEMPs) and polypropylene microparticles (PPMPs) as well as heat- or irradiation-aged microparticles (ag-PEMPs and ag-PPMPs) were used to quantify Hb adsorption. Polypropylene filters (PP-filters) were used to measure the oxygenation of adsorbed Hb. Microstructured plastics were characterized using optical microscopy, SAXS, ATR-FTIR, XPS, and Raman spectroscopy. Adsorption isotherms showed that the Hb corona thickness is larger on PPMPs than on PEMPs and Hb has a higher affinity for PPMPs than for PEMPs. Hb had a lower affinity for ag-PEMPs and ag-PPMPs, but they can be adsorbed in larger amounts. The presence of partial charges on the plastic surface and the oxidation rate of microplastics may explain these differences. Tonometry experiments using an original method, the diffuse reflection of light, showed that adsorbed Hb on PP-filters retains its cooperativity, but its affinity for O2 decreases significantly.

Background: Spinal cord ischemia (SCI) is a severe complication after fenestrated/branched endovascular repair (f/bEVAR). The underlying causes of SCI are still under investigation. This study aimed to evaluate intra- and early post-operative parameters that may affect SCI evolution. Methods: A single-center retrospective analysis was conducted including SCI patients with complete anesthesiologic records (1 January 2011 to 31 December 2023). Values of intra-operative glucose, hemoglobin, lactate, activated clotting time (ACT), and the need for transfusion were collected. The cohort was compared to a matched cohort of non-SCI patients. Results: Fifty-one patients with SCI and complete anesthesiologic records were included (mean age: 69.8 ± 6.2 years; 39.2% male). Intra-operative glucose value < 110 mg/dL (AUC: 0.73; sensitivity 91%, specificity of 83%) and hemoglobin value > 8.5 mg/dL (AUC: 0.61; sensitivity 83%, specificity 78%) were protective for Grade 3 SCI. Twenty-three patients with SCI were matched to 23 patients without SCI. SCI patients presented significantly higher glucose levels intra-operatively (glucose mean value: SCI 150 ± 46 mg/dL vs. non-SCI: 122 ± 30 mg/dL, p = 0.005). ACT (SCI 259 ± 31 svs. non-SCI 288 ± 28 s, p = 0.001), volume input (SCI 4030 ± 1430 mL vs. non-SCI 3020 ± 113 mL, p = 0.009), and need for transfusion (SCI: 52.5% vs. 4.3%, p < 0.001) were related to SCI. Higher glucose levels were detected among patients with SCI, at 24 (SCI: 142 ± 30 mg/dL vs. non-SCI: 118 ± 26 mg/dL, p=0.004) and 48 h (SCI: 140 ± 29 mg/dL vs. non-SCI: 112 ± 20 mg/dL, p < 0.001) post-operatively. Conclusions: SCI is a multifactorial complication after f/bEVAR. Intra-operative and early post-operative glucose levels may be related to SCI evolution. Targeted glucose < 110 mg/dL may be protective for Grade 3 SCI.

OBJECTIVE: Evidence is scarce regarding the association between anemia and alterations in cognitive level among hospitalized older patients. We aimed to evaluate the associations between baseline hemoglobin (Hb) levels and changes in cognitive level in patients undergoing rehabilitation after stroke.
METHODS: A retrospective cohort study was conducted, encompassing consecutively hospitalized post-stroke patients. Data on serum Hb levels were extracted from medical records, specifically tests conducted within 24 hours of admission. Primary outcomes included discharge scores for cognitive function assessed by the cognitive domain of the Functional Independence Measure (FIM-cognition) and the corresponding change in FIM-cognition during hospitalization. Another outcome measure was the length of hospital stay. Multivariate linear regression analyses were employed to assess the association between Hb levels at admission and the designated outcomes, adjusting for potential confounding factors.
RESULTS: Data from 955 patients (mean age 73.2 years; 53.6% men) were included in the analysis. The median Hb level at admission was 13.3 [11.9, 14.5] g/dL. After fully adjusting for confounding factors, the baseline Hb level was significantly and positively associated with FIM-cognition at discharge (β = 0.045, p = 0.025) and its gain (β = 0.073, p = 0.025). Further, the baseline Hb level was independently and negatively associated with length of hospital stay (β = -0.013, p = 0.026).
CONCLUSIONS: Elevated baseline Hb levels are correlated with preserved cognitive level and shorter hospital stays in post-stroke patients. Evaluating anemia at the outset serves as a crucial prognostic indicator.

Thalassemic diseases are characterized by a reduced (β+) or absent (β0) synthesis of the globin chains of hemoglobin (Hb) due to genetic mutations. β-thalassemia was more frequent in the Mediterranean area, but now it is diffused worldwide. Three possible genetic forms can be distinguished: β0/β0, the most severe (Cooley\'s disease); β0/β+ of intermediate severity; β+/β+ associated with β-thalassemia intermedia or minor. Recently, a clinical non-genetic classification has been proposed: transfusion-dependent thalassemia (TDT), requiring regular lifetime blood transfusions, and non-transfusion-dependent thalassemia (NTDT), requiring occasional transfusions to manage acute cases. In this report, we studied a patient whose blood count indicated a severe anemia but also showed thrombocytosis, leukocytosis, and an elevated number of nucleated red blood cells (NRBC). These altered blood parameters suggested initially a possible diagnosis of hemoglobinopathy or myeloproliferative syndrome. The molecular and genetic analyses demonstrated the presence of HbF (5.3%) and HbA2 (7.7%) and the presence of the homozygote mutation (IVS1.6T>C) in the β-globin gene. According to these data, a diagnosis of β-thalassemia intermedia form has been proposed. Nevertheless, the clinical condition, the presence of thrombocytosis, leukocytosis, an elevated number of NRBC, and the frequent blood transfusions lead to reclassification of the patient as TDT subject. Consequently, this result suggests that a unique genotype-phenotype correlation is not possible in the presence of β+mutations since other concomitant pathologies can exacerbate the disease.

Fish skin plays an important role in defending against pathogens in water, primarily through the secretion of skin mucus containing various immune-related factors. Local immune responses in the skin activate systemic immune responses by inflammatory cytokines. However, it remains unclear whether immune responses in the skin occur after systemic immune responses caused by pathogen invasion into the fish body. This study aimed to clarify the relationship between systemic immune responses and skin responses after intraperitoneal injection of formalin-killed cells (FKC) of Vibrio anguillarum. Although systemic inflammatory responses were observed in the spleen after injection, expression changes in the skin did not show significant differences. In contrast, expression of hemoglobin subunit genes significantly increased in the skin after FKC injection, suggesting that erythrocytes infiltrate extravascularly.

BACKGROUND: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration.
METHODS: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively.
RESULTS: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower.
CONCLUSIONS: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies.
BACKGROUND: ClinicalTrials.gov: NCT02101268.
Patients with the rare blood cancer myelofibrosis often experience symptoms such as tiredness, an increase in the size of their spleens (an organ involved in filtering the blood), and anemia (too few red blood cells). One type of treatment for myelofibrosis, called a Janus kinase (JAK) inhibitor, can help patients to feel better and reduce the size of their spleens, but some JAK inhibitors do not help with anemia and may make it worse. In those situations, patients may continue to take their JAK inhibitor but also receive another type of treatment, called an anemia supportive therapy, and may also receive red blood cell transfusions. This study compared 2 treatment approaches, continuing the JAK inhibitor ruxolitinib and adding an anemia supportive therapy and/or transfusions versus switching to another treatment called momelotinib, in 2 groups of patients from a clinical trial: (1) patients with levels of hemoglobin (a red blood cell protein) at the start of the trial that indicated that they had anemia, and (2) patients who were already receiving red blood cell transfusions at the start of the trial. In both groups, more patients did not need red blood cell transfusions anymore at week 24 with momelotinib, and their hemoglobin levels on average became higher over time. More patients also had improvements in spleen size and symptoms with momelotinib. Overall, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using supportive therapies and/or red blood cell transfusions to treat anemia.

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 red blood cell (RBC) transfusion for patients receiving venovenous extracorporeal membrane oxygenation (VV-ECMO) is controversial. Previous guidelines recommended transfusing to a normal hemoglobin, but recent studies suggest more RBC transfusions are associated with increased adverse outcomes.
OBJECTIVE: Is implementation of different institutional RBC transfusion thresholds for patients receiving VV-ECMO associated with changes in RBC utilization and patient outcomes?
METHODS: Single-center retrospective study of patients receiving VV-ECMO using segmented regression to test associations between implementation of institutional transfusion thresholds and trends in RBC utilization. Associations with secondary outcomes, including in-hospital survival, were also assessed.
RESULTS: The study included 229 patients: 91 in the \"no threshold (NT)\" cohort, 48 in the \"hemoglobin <8 g/dL (<8 g/dL)\" cohort and 90 in the \"hemoglobin <7 g/dL (<7 g/dL)\" cohort. Despite a decrease in RBC/ECMO day following implementation of different thresholds, (mean +/- SD; 0.6 +/- 1.0 in the NT cohort, 0.3 +/- 0.8 in the <8 g/dL cohort, and 0.3 +/- 1.1 in the <7 g/dL cohort, p < 0.001), segmented regression showed no association between implementation of transfusion thresholds and changes in trends in RBC/ECMO day. We observed an increased hazard of death in the NT cohort compared to the <8 g/dL cohort (aHR: 2.08, 95% CI: 1.12-3.88), and in the <7 g/dL cohort compared to the <8g/dL cohort (aHR: 1.93, 95% CI: 1.02-3.62). There was no difference in the hazard of death between the NT and <7 g/dL cohorts (aHR: 1.08, 95% CI: 0.69-1.69).
CONCLUSIONS: We observed a decrease in RBC/ECMO day 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 investigating optimal RBC transfusion practices for patients supported with VV-ECMO.

The relationship between in-hospital hemoglobin (Hb) drift and outcomes in patients undergoing surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH) is not well studied. This study aims to investigate the association between Hb drift and mortality in this patient population. We conducted a cohort study encompassing adult patients diagnosed with aSAH who were admitted to a university hospital. These patients were stratified into distinct groups based on their Hb drift levels. We employed logistic and Cox proportional hazard models to assess the relationship between Hb drift and outcomes. Additionally, propensity score matching (PSM) was utilized to ensure comparability between patient groups. The discriminative performance of different models was evaluated using C-statistics, integrated discrimination improvement (IDI), and net reclassification improvement (NRI). Overall, our cohort comprised 671 patients, of whom 165 (24.6%) demonstrated an in-hospital Hb drift exceeding 25%. The analyses revealed elevated Hb drift was independently associated with higher likelihood of follow-up mortality (aOR: 3.29, 95% CI: 1.65 to 6.56; P = 0.001) and in-hospital mortality (aOR: 3.44, 95% CI: 1.55 to 7.63; P = 0.002). PSM analysis yielded similar results. Additionally, patients with Hb drift exhibited a notable decrease in survival rate compared to those without Hb drift (aHR: 3.99, 95% CI 2.30 to 6.70; P < 0.001). Furthermore, the inclusion of Hb drift significantly improved the C-statistic (P = 0.037), IDI (2.78%; P = 0.004) and NRI metrics (41.86%; P < 0.001) for mortality prediction. In summary, our results highlight that an in-hospital Hb drift exceeding 25% serves as an independent predictor of mortality in patients who have undergone surgical clipping for aSAH.