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Frontiers in Cardiovascular Medicine 2022Recent studies suggest that the pivotal mechanism of sodium glucose co-transporter-2 inhibitors (SGLT-2i) favorable action in patients with heart failure (HF) and type 2...
BACKGROUND
Recent studies suggest that the pivotal mechanism of sodium glucose co-transporter-2 inhibitors (SGLT-2i) favorable action in patients with heart failure (HF) and type 2 diabetes mellitus (DM) is the stimulation of erythropoiesis an early increase in erythropoietin (EPO) production which leads to hematocrit rise. Red blood cell distribution width (RDW) is a simple hematological parameter which reflects the heterogeneity of the red blood cell size (anisocytosis). Since, EPO has been also implicated in the pathophysiology of RDW increase, the current mechanistic study examined the effect of SGLT-2i administration on red blood cells size (RDW) in patients with HF and DM.
METHODS
The present was a prospective single-center study. Patients (N=110) were randomly assigned to dapagliflozin (10 mg a day on top of antidiabetic treatment) or the control group. Inclusion criteria were: (a) age > 18 years, (b) history of type 2 DM and hospitalization for HF exacerbation within 6 months. The evaluation of patients (at baseline, 6 and 12 months) included clinical assessment, laboratory blood tests, and echocardiography. Data were modeled using mixed linear models with dependent variable the RDW index. In order to find factors independently associated with prognosis (1-year death or HF rehospitalization), multiple logistic regression was conducted with death or HF rehospitalization as dependent variable.
RESULTS
An RDW increase both after 6 and after 12 months was observed in the SGLT-2i (dapagliflozin) group ( < 0.001 for all time comparisons), whereas RDW didn't change significantly in the control group. The increase in RDW was positively correlated with EPO, while negatively correlated with ferritin and folic acid ( < 0.005 for all). Baseline RDW was significantly associated with 1-year death or rehospitalization, after adjusting for group (SGLT-2i vs. control), age, gender, smoking and BMI at baseline.
CONCLUSION
RDW increased with time in patients with HF and DM who received SGLT-2i (dapagliflozin). The increased RDW rates in these patients may stem from the induction of hemopoiesis from dapagliflozin. Baseline RDW was found to be independently associated with outcome in patients with HF and DM.
PubMed: 36247420
DOI: 10.3389/fcvm.2022.984092 -
Journal of Toxicology 2022Away from hemorheological properties, the effect of heroin addiction on erythrocytes is poorly investigated. This study aimed to investigate the oxidative impacts of...
Away from hemorheological properties, the effect of heroin addiction on erythrocytes is poorly investigated. This study aimed to investigate the oxidative impacts of heroin administration on erythrocytes. Study subjects included chronic intravenous heroin addicts and control subjects. Hematological analysis and redox parameters were measured, including serum concentration of methemoglobin ([MethHb]), serum glutathione peroxidase-1 ([GPX-1]), serum glutathione peroxidase (GPX) activity, erythrocytic protein carbonyl content, and oxidized to reduced glutathione (GSSG/GSH) ratio. Hematological analysis revealed that addicts had a significantly higher red cell distribution width, consistent with the mild anisocytosis and poikilocytosis of erythrocytes. As compared to control subjects, significantly higher levels of serum [Met-Hb], [GPX-1], and GPX activity ( < 0.001) were reported among addicted subjects. A significant association between [MetHb] and GPX activity was observed with = 0.764 ( < 0.001). Furthermore, significantly higher erythrocytic protein carbonyl contents and GSSG/GSH ratio were evident among heroin addicts ( < 0.005) that were significantly associated with = 0.429 (=0.01). Results demonstrate preliminary evidence that heroin addiction is implicated in impaired redox status of erythrocytes. Considering the pharmacokinetics of heroin, erythrocytic antioxidant mechanisms, and turnover rate, further investigation is required to evaluate the extent and clinical outcomes, especially upon over-dose administration.
PubMed: 36212505
DOI: 10.1155/2022/3996051 -
Journal of Blood Medicine 2022RDW is critical to the clinical diagnosis and progression of ESRD. There is currently little data on the relationship between RDW and ESRD in sub-Saharan Africa. Because...
BACKGROUND
RDW is critical to the clinical diagnosis and progression of ESRD. There is currently little data on the relationship between RDW and ESRD in sub-Saharan Africa. Because of this, the present study evaluates RDW in patients with ESRD and associated factors in Addis Ababa, Ethiopia.
METHODS
The hospital-based cross-sectional study design was conducted on a total of 83 patients. RDW, MCV, SCR, BUN, GFR, FBS and serum albumin were determined. Blood pressure (mmHg), weight (kg), height (m), MUAC (cm) and BMI (kg/m2) were also measured. Data entry was via Epi-data version 3.4 and analyzed with SPSS version 26.0. A multivariate logistic regression analysis with a p-value < 0.05 at a 95% confidence interval was used to identify the associated factors of RDW.
RESULTS
A total of 83 ESRD patients participated, with a response rate of 95.4%. RDW ranged from 15.5% to 23.6% with a mean of 17.40% + 1.46%. Anisocytosis was present in 98.8% of patients. Of 83 patients, 66.3% were hypertensive, 20.5% had diabetes, and the remaining 13.3% had other conditions (glomerulonephritis and peripheral vascular disease). The mean GFR value was 5.20 mL/min/1.73 + 1.58. RDW showed a significant association with GFR (AOR: 4.6, 95% CI [1.27, 20.74], P = 0.047), alcohol consumption (AOR: 13.4, P = 0.012, 95% CI [1.97, 22.62]), recurrent kidney disease (AOR=25.6, P=0.016, 95% CI [1.85, 53.71]) and use of medication (AOR=00.2, P=0.044), 95% CI [0.03, 0.95]).
CONCLUSION
RDW showed a significant association with GFR, recurrent kidney disease, alcohol consumption, and medication use in hemodialysis-dependent ESRD patients. The mechanisms of RDW disruption in ESRD patients need further investigation.
PubMed: 36210887
DOI: 10.2147/JBM.S373280 -
Journal of Medical Case Reports Aug 2022Diabetes mellitus is the most common metabolic disease globally, while glucose-6-phosphate dehydrogenase deficiency, an X-linked inherited disorder, is the most common...
BACKGROUND
Diabetes mellitus is the most common metabolic disease globally, while glucose-6-phosphate dehydrogenase deficiency, an X-linked inherited disorder, is the most common erythrocyte enzyme defect. The association between the two in children has been infrequently reported.
CASE PRESENTATION
We report the case of a 10-year-old boy of Iraqi descent who presented to our emergency department with new-onset type 1 diabetes mellitus without Diabetic Keto Acidosis. He was treated with subcutaneous insulin and discharged. Eleven days after hospitalization, he was found to be jaundiced during his home visit. Hence, he was referred to the pediatric unit, and his hemoglobin had declined from 130 g/L at the previous admission to 81 g/L. Blood tests revealed low haptoglobin, and his peripheral blood film showed anisocytosis, polychromasia, and occasional red cell fragments suggestive of acute hemolysis. His glucose-6-phosphate dehydrogenase activity was very low, and his subsequent genetic tests confirmed Mediterranean-type glucose-6-phosphate dehydrogenase deficiency.
CONCLUSION
Glucose-6-phosphate dehydrogenase deficiency in people with diabetes mellitus has been underreported in the literature so far, and screening of glucose-6-phosphate dehydrogenase deficiency should be considered on diagnosis of diabetes mellitus, especially in boys of African, Mediterranean, or Asian descent.
Topics: Child; Diabetes Mellitus, Type 1; Diabetic Ketoacidosis; Glucosephosphate Dehydrogenase Deficiency; Hemoglobins; Hemolysis; Humans; Male
PubMed: 36008815
DOI: 10.1186/s13256-022-03549-7 -
Wiener Klinische Wochenschrift Oct 2023Little is known about the potential impact of the red blood cell distribution width (RDW) and pre-existing comorbidities on the late-phase survival of polytraumatized...
INTRODUCTION
Little is known about the potential impact of the red blood cell distribution width (RDW) and pre-existing comorbidities on the late-phase survival of polytraumatized patients.
METHODS
A total of 173 polytraumatized patients were included retrospectively in this cohort study in a level I trauma center from January 2012 to December 2015. The Charlson comorbidity index (CCI) scores and RDW values were evaluated.
RESULTS
Out of all polytraumatized patients (n = 173), 72.8% (n = 126) were male, the mean ISS was 31.7 points (range 17-75) and the mean age was 45.1 years (range 18-93 years). Significantly higher RDW values (13.90 vs. 13.37; p = 0.006) and higher CCI scores (3.38 vs. 0.49; p < 0.001) were seen in elderly polytraumatized patients (age > 55 years). RDW values > 13.75% (p = 0.033) and CCI scores > 2 points (p = 0.001) were found to have a significant influence on the late-phase survival of polytraumatized patients. Age > 55 years (p = 0.009, HR 0.312; 95% confidence interval (CI) 0.130-0.749) and the presence of severe traumatic brain injury (TBI) (p = 0.007; HR 0.185; 95% CI 0.054-0.635) remained as independent prognostic factors on the late-phase survival after multivariate analysis.
CONCLUSION
Even younger elderly polytraumatized patients (> 55 years of age) showed significant higher RDW values and higher CCI scores. In addition to the presence of severe TBI and age > 55 years, RDW value > 13.75% on admission and CCI score > 2 might help to identify the "younger" frail polytraumatized patient at risk.
Topics: Humans; Male; Aged; Adolescent; Young Adult; Adult; Middle Aged; Aged, 80 and over; Female; Retrospective Studies; Prognosis; Cohort Studies; Frail Elderly; Trauma Centers; Erythrocyte Indices; Comorbidity; Brain Injuries, Traumatic; Erythrocytes
PubMed: 35943632
DOI: 10.1007/s00508-022-02063-6 -
JCI Insight Sep 2022Increased red cell distribution width (RDW), which measures erythrocyte mean corpuscular volume (MCV) variability (anisocytosis), has been linked to early mortality in...
Increased red cell distribution width (RDW), which measures erythrocyte mean corpuscular volume (MCV) variability (anisocytosis), has been linked to early mortality in many diseases and in older adults through unknown mechanisms. Hypoxic stress has been proposed as a potential mechanism. However, experimental models to investigate the link between increased RDW and reduced survival are lacking. Here, we show that lifelong hypobaric hypoxia (~10% O2) increased erythrocyte numbers, hemoglobin, and RDW, while reducing longevity in male mice. Compound heterozygous knockout (hKO) mutations in succinate dehydrogenase (Sdh; mitochondrial complex II) genes Sdhb, Sdhc, and Sdhd reduced Sdh subunit protein levels, reduced RDW, and increased healthy life span compared with WT mice in chronic hypoxia. RDW-SD, a direct measure of MCV variability, and the SD of MCV showed the most statistically significant reductions in Sdh hKO mice. Tissue metabolomic profiling of 147 common metabolites showed the largest increase in succinate with elevated succinate/fumarate and succinate/oxoglutarate (2-ketoglutarate) ratios in Sdh hKO mice. These results demonstrate that mitochondrial complex II level is an underlying determinant of both RDW and healthy life span in hypoxia and suggest that therapeutic targeting of Sdh might reduce high RDW-associated clinical mortality in hypoxic diseases.
Topics: Animals; Erythrocyte Indices; Hypoxia; Longevity; Male; Mice; Succinate Dehydrogenase; Succinates
PubMed: 35881479
DOI: 10.1172/jci.insight.158737 -
BMC Infectious Diseases Jul 2022
PubMed: 35799137
DOI: 10.1186/s12879-022-07563-4 -
BMC Infectious Diseases Jun 2022Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A...
BACKGROUND
Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications.
METHODS
We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C.
RESULTS
We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78-100%) and 80% specificity (95% CI 69-88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80-100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls.
CONCLUSIONS
Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.
Topics: COVID-19; Child; Humans; Monocytes; SARS-CoV-2; Systemic Inflammatory Response Syndrome
PubMed: 35725405
DOI: 10.1186/s12879-022-07526-9 -
European Journal of Translational... Jun 2022We aimed to review the records of cancer and kidney transplant patients of out of 1135 COVID-19 patients, who were referred to our hospital (Valiasr) in Zanjan, from...
Red cell distribution width, a predictive factor in immunocompromised patients with COVID-19: A comparison retrospective study between cancer and kidney transplant patients.
We aimed to review the records of cancer and kidney transplant patients of out of 1135 COVID-19 patients, who were referred to our hospital (Valiasr) in Zanjan, from March 16th, 2020, to June 11th, 2020. This was single-center, historical cohort study. Patients were divided into different subgroups and compared of disease outcomes. The only predictor of death was lactate dehydrogenase (LDH). The rate of red cell distribution width (RDW) in patients with active cancer was higher than kidney transplant patients and was statistically significant. There was no statistically significant difference in mortality between active and non-active cancer groups. Female sex and low SpO2 has increased the chances of ICU admission. Patients with active cancer generally have severe and more complicated disease and RDW can be a predictable option.
PubMed: 35723624
DOI: 10.4081/ejtm.2022.10582 -
International Journal of Molecular... May 2022Prime editing was used to insert and correct various pathogenic mutations except for beta-thalassemia variants, which disrupt functional beta-globin and prevent...
Prime editing was used to insert and correct various pathogenic mutations except for beta-thalassemia variants, which disrupt functional beta-globin and prevent hemoglobin assembly in erythrocytes. This study investigated the effect of gene correction using prime editor version 3 (PE3) in a mouse model with the human beta-thalassemia IVS-II-654 mutation (C > T). The T conversion generates a 5′ donor site at intron 2 of the beta-globin gene resulting in aberrant splicing of pre-mRNA, which affects beta-globin expression. We microinjected PE3 components (pegRNA, nick sgRNA, and PE2 mRNA) into the zygotes from IVS-II-654 mice to generate mutation-edited mice. Genome sequencing of the IVS-II-654 site showed that PE3 installed the correction (T > C), with an editing efficiency of 14.29%. Reverse transcription-PCR analysis showed that the PE3-induced conversion restored normal splicing of beta-globin mRNA. Subsequent comprehensive phenotypic analysis of thalassemia symptoms, including anemic hematological parameters, anisocytosis, splenomegaly, cardiac hypertrophy, extramedullary hematopoiesis, and iron overload, showed that the corrected IVS-II-654 mice had a normal phenotype identical to the wild type mice. Off-target analysis of pegRNA and nick sgRNA additionally showed the genomic safety of PE3. These results suggest that correction of beta-thalassemia mutation by PE3 may be a straightforward therapeutic strategy for this disease.
PubMed: 35682629
DOI: 10.3390/ijms23115948