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Background Thalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden. Considering its high prevalence in low and middle-income countries, a cheap, accurate and high-throughput screening test of thalassaemia prior to a more expensive confirmatory diagnostic test is urgently needed. Methods In this study, we constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains in blood, and for the first time, evaluated its diagnostic efficacy in 674 thalassaemia (including both asymptomatic carriers and symptomatic patients) and control samples collected in three hospitals. Parameters related to haemoglobin imbalance (α-globin, β-globin, γ-globin, α/β and α-β) were used for feature selection before classification model construction with 8 machine learning methods in cohort 1 and further model efficiency validation in cohort 2. Results The logistic regression model with 5 haemoglobin peak features achieved good classification performance in validation cohort 2 (AUC 0.99, 95% CI 0.98–1, sensitivity 98.7%, specificity 95.5%). Furthermore, the logistic regression model with 6 haemoglobin peak features was also constructed to specifically identify β-thalassaemia (AUC 0.94, 95% CI 0.91–0.97, sensitivity 96.5%, specificity 87.8% in validation cohort 2). Conclusions For the first time, we constructed an inexpensive, accurate and high-throughput classification model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains and demonstrated its great potential in rapid screening of thalassaemia in large populations.Key messagesThalassaemia is one of the most common inherited monogenic diseases worldwide with a heavy global health burden.We constructed a machine learning model based on MALDI-TOF mass spectrometry quantification of haemoglobin chains to screen for thalassaemia.

Background The purpose is to compare the efficacy and safety of mini percutaneous nephrolithotomy (mini-PCNL) versus standard percutaneous nephrolithotomy (standard-PCNL) in patients with renal stones >2cm. Materials and Methods A systematic literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library databases to identify relevant studies before March 8, 2021. Stone-free rate (SFR), operation time, fever rate, hemoglobin drop, blood transfusion rate, and hospitalization time were used as outcomes to compare mini-PCNL and standard-PCNL. The meta-analysis was performed using the Review Manager version 5.4. Results Seven randomized controlled trials were included in our meta-analysis, involving 1407 mini-PCNL cases and 1436 standard-PCNL cases. Our results reveal that, for renal stones >2cm, mini-PCNL has a similar SFR (risk ratio (RR)=1.01, 95% confidence interval (CI): 0.98 to 1.04, p=0.57) and fever rate (RR=1.22, 95% CI: 0.97-1.51, p=0.08). Standard-PCNL was associated with a significantly shorter operating time (weighted mean difference (WMD)=8.23, 95% CI: 3.44 to 13.01, p 2cm renal stones, mini-PCNL should be considered an effective and reliable alternative to standard-PCNL (30F). It achieves a comparable SFR to standard-PCNL, but with less blood loss, lower transfusion rate, and shorter hospitalization. However, the mini-PCNL does not show a significant advantage over the 24F standard-PCNL. On the contrary, this procedure takes a longer operation time. Trial registration This meta-analysis was reported consistent with the PRISMA statement and was registered on PROSPERO, with registration number 2021CRD42021234893.

BACKGROUND Although some studies have described the association between serum ferritin levels and specific disorders in child and adolescent psychiatry, few have focused on mental health with low serum ferritin levels in children and adolescents. This study examined the effects of iron administration on psychological state of children and adolescents with reduced serum ferritin concentration. METHODS This prospective study evaluated 19 participants aged 6-15 years with serum ferritin levels

OBJECTIVES To determine potential risk factors for severe hemolysis during pediatric cardiopulmonary bypass and examine whether supraphysiologic levels of oxygen and cardiopulmonary bypass duration are associated with hemolysis. DESIGN Prospective observational study. SETTING Cardiac ICU in a university-affiliated children's hospital. PATIENTS Greater than 1 month to less than 18 years old patients undergoing cardiopulmonary bypass for cardiac surgery. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Plasma samples from 100 patients to assess cell-free plasma hemoglobin levels were obtained at start cardiopulmonary bypass, at the end of cardiopulmonary bypass, and 2 and 24 hours after reperfusion. Arterial blood gas samples were obtained before and every 30 minutes during cardiopulmonary bypass. Patient demographics and laboratory data were collected from the electronic medical record. Plasma hemoglobin levels peaked at the end of cardiopulmonary bypass and haptoglobin levels continued to fall throughout all time points. There were 44 patients with severe hemolysis (change in cell-free plasma hemoglobin > 50 mg/dL). Younger age (odds ratio/SD 0.45 [95% CI, 0.25-0.81]) and higher mean PaO2 × cardiopulmonary bypass duration (31.11 [1.46-664.64]) were identified as risk factors for severe hemolysis in multivariable analysis. Severe hemolysis was associated with longer hospital and ICU lengths of stay as well as acute kidney injury. CONCLUSIONS We observed younger age and the exposure to both oxygen and duration of cardiopulmonary bypass as risk factors for hemolysis. Oxygen delivery through the cardiopulmonary bypass circuit is an easily modifiable risk factor. Its role in the production of reactive oxygen species that could alter the erythrocyte membrane deserves further examination in larger prospective studies.

A group of inherited blood defects is known as Thalassemia is among the world’s most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Introduction and objectives Prevalence of hypertension increases as glomerular filtration rate (GFR) declines. Renalase metabolizes catecholamines and have an important role in blood pressure (BP) regulation. The purpose of the study was to evaluate the effect of kidney transplantation on renalase levels and BP in kidney donors and recipients. Materials and methods Twenty kidney transplant recipients and their donors were included in the study. Serum renalase levels and ambulatory BP values were measured in both donors and recipients before and after transplantation. Factor associated with change in renalase and BP levels were also evaluated. Results In donors; mean GFR and hemoglobin levels decreased while night-time systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels and serum renalase levels increased simultaneously after nephrectomy. Day-time SBP and DBP levels did not changed and the night/day ratio of mean arterial pressure (MAP) increased significantly. In recipients, mean GFR increased, while mean serum renalase levels, creatinine and BP levels decreased after transplantation. Correlation analysis revealed that changes in MAP correlated with alteration in serum renalase levels and GFR. Conclusions After transplantation, serum renalase levels increased in donors and decreased in recipients. The renalase levels are associated with change in MAP and circadian rhythm of BP in donors and recipients.

Colorectal cancer (CRC) screening has been demonstrated to reduce CRC incidence and mortality. However, besides such benefits, CRC screening is also associated with potential harmful effects. In an ideal world, screening would only be directed to the small proportion of the population that might potentially benefit. Risk-based screening can be seen as a first step towards this ideal world, by redistributing screening resources from low-risk to high-risk individuals. In theory, this should result in scarce resources being used in individuals who benefit most, while intensity of screening is reduced in individuals who benefit less, hence improving the benefit-harm ratio among all invitees. Available strategies that have been proposed for risk-based CRC screening include using information on age, sex, prior screening history, lifestyle and/or genetic information. Implementation of risk-based screening requires careful consideration of reliable risk prediction models, participation with screening and informed decision-making. While it is important to recognise the limitations of current approaches, available evidence suggests that it might be feasible to start planning the introduction of tailored strategies within screening programmes. Implementing risk-based screening based on age, sex and prior screening history alone would already represent a substantial improvement over current uniform screening approaches. We propose that it is time that screening programmes start there and continue striving towards more comprehensive approaches embedding primary prevention as an effective approach to lower risk for everyone.

Introduction The clinical presentation of lower gastrointestinal bleeding (LGIB) is variable in severity, cause and potential investigations. The British Society of Gastroenterology recently published LGIB guidelines, recommending CT angiography (CT-A) for haemodynamically unstable patients, defined by shock index (SI) greater than 1. The aim of this study was to assess the use and role of CT-A in diagnosing LGIB, by assessing the pickup rate of active LGIB defined by contrast extravasation or ‘blush’ and to determine any association between positive CT-A with various patient and clinical characteristics. Methods A retrospective analysis was carried out of 4 years of LGIB admissions. Demographics, inpatient observations and use of blood products were acquired. Vital signs nearest the time of CT-A plus abnormal vital signs preceding imaging were used to calculate SI, Age SI, National Early Warning Score 2 (NEWS2) and Standardised Early Warning Score (SEWS). A consultant gastrointestinal radiologist further reviewed all consultant-reported scans. Results In total, 930 patients were admitted with LGIB. Median age was 71 years and 51% were male; 179 (19.2%) patients received red blood cell transfusion and 93 patients (10%) underwent CT-A, who were older and were likely to be hypotensive and receive red cell transfusions. Following exclusions, 92 CT-As were included in the analysis. Nine (9.8%) were positive. Univariate analysis showed no association between positive CT-A and any scoring system. A multivariate analysis, including age and gender, showed association between both NEWS2 and SEWS scores with positive CT-A. Conclusion In our analysis of the typical LGIB population, CT-A has shown relatively low pick up rate of active bleeding. CT-A clearly has a role in the investigation of LGIB, but selection remains challenging.

Objective. The purpose was to evaluate the treatment effect of iron proteinsuccinylate oral solution combined with vitamin A and D drops on children with nutritional iron deficiency anemia. Methods. 124 children treated in the outpatient department of our hospital from January 2017 to January 2020 were selected as the study subjects. They were randomly divided into control and observation two groups. The control group was treated with iron proteinsuccinylate oral solution (1.5 mL/kg) in the morning and evening, respectively. The observation group received adjuvant treatment with oral vitamin A and D drops based on the treatment of the control group. The treatment effect of proteinsuccinylate oral solution combined with vitamin A and D drops was evaluated by the serum iron (SI), serum ferritin (SF), and transferrin (TRF) levels, the values of CD3+, CD4+, and CD4+/CD8+, and other evaluation indicators. Results. After treatment, the SI and SF levels of children in both groups significantly increased ( P < 0.01 ) while the TRF level significantly decreased ( P < 0.01 ), and the SI and SF levels in the observation group increased more significantly, and the TRF level decreased more significantly compared with those in the control group ( P < 0.01 ). After treatment, the values of CD3+, CD4+, and CD4+/CD8+ of children in both groups significantly increased compared with those before treatment ( P < 0.01 ), and the values of CD3+, CD4+, and CD4+/CD8+ increased more significantly in the observation group compared with those in the control group ( P < 0.01 ). In addition, the evaluation results of treatment effect showed that the markedly effective rate in the observation group was significantly higher than that in the control group ( P < 0.01 ). Conclusion. Iron proteinsuccinylate oral solution combined with vitamin A and D drops can better improve the anemia symptoms in children, with high application value.

Background Iron deficiency anemia (IDA) is a public health problem in children and adolescents that is characterized by reduced hemoglobin (Hb) levels. Non-invasive monitoring devices can measure Hb levels continuously without pain or discomfort; however, little is known about their accuracy in children and adolescents. This study estimated the accuracy of a non-invasive Hb monitor in this age group. Methods Participants were outpatients visiting the Tokyo Metropolitan Children's Medical Center for blood tests between January and March 2019. Hb levels were measured using both non-invasive Astrim Fit monitoring devices and invasive blood collection followed by automated analysis. Bland–Altman analysis assessed the agreement between the two measurements. Results Overall, 120 schoolchildren (9–15 years old, 51 % female) were enrolled. The non-invasive measuring device recorded Hb levels of 13.5 ± 1.6 g/dL (mean ± standard deviation [SD]), while the mean Hb level obtained from the collected blood was 13.7 ± 1.7 g/dL. Therefore, the mean difference of bias and SD of precision was 0.17 ± 1.95 g/dL. Values of lower and upper limits of agreement were −3.65 and 3.99, respectively. There was no systematic fixed or proportion bias. Fifty-nine participants (49 %) had a relative error of ± 0.10. Conclusion The Astrim Fit non-invasive Hb monitor can be used to evaluate Hb levels among schoolchildren for health promotion or research purposes because of its extremely low bias (or precision), no systematic biases (including fixed or proportion biases), and positive correlation between non-invasive monitoring and blood drawing. However, it is difficult to assess Hb levels in children and adolescents using the Astrim Fit device for diagnostic purposes.

Background Cell-free heme-containing proteins mediate endothelial injury in a variety of disease states including subarachnoid hemorrhage and sepsis by increasing endothelial permeability. Inflammatory cells are also attracted to sites of vascular injury by monocyte chemotactic protein 1 (MCP-1) and other chemokines. We have identified a novel peptide hormone, adropin, that protects against hemoglobin-induced endothelial permeability and MCP-1-induced macrophage migration. Methods Human microvascular endothelial cells were exposed to cell-free hemoglobin (CFH) with and without adropin treatment before measuring monolayer permeability using a FITC-dextran tracer assay. mRNA and culture media were collected for molecular studies. We also assessed the effect of adropin on macrophage movement across the endothelial monolayer using an MCP-1-induced migration assay. Results CFH exposure decreases adropin expression and increases paracellular permeability of human endothelial cells. Treating cells with synthetic adropin protects against the increased permeability observed during the natural injury progression. Cell viability was similar in all groups and Hmox1 expression was not affected by adropin treatment. MCP-1 potently induced macrophage migration across the endothelial monolayer and adropin treatment effectively reduced this phenomenon. Conclusions Endothelial injury is a hallmark of many disease states. Our results suggest that adropin treatment could be a valuable strategy in preventing heme-mediated endothelial injury and macrophage infiltration. Further investigation of adropin therapy in animal models and human tissue specimens is needed.

Background Plasmodium falciparum gametocytaemia has been associated with anaemia. The aim of this review was to synthesize available evidence on the comparative effect of dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL) on gametocyte clearance and haemoglobin recovery in children with uncomplicated P. falciparum malaria in Africa. Methods A systematic literature search was undertaken to identify relevant articles from online databases. The search was performed from August 2020 to 30 April 2021. Extracted data from eligible studies were pooled as risk ratios with 95% confidence intervals (CI). Results Gametocyte carriage was reduced in both treatment groups, with no significant difference found between the groups. However, on days 28 and 42, a significant increase in serum haemoglobin level from baseline was observed in the DHA-PQ group (standardized mean difference 0.15, 95% CI 0.05–0.26; participants=2715; studies=4; I2=32%, high quality of evidence) compared with the AL group (mean difference 0.35, 95% CI 0.12–0.59; participants=1434; studies=3; I2=35%, high quality of evidence). Conclusion DHA-PQ had a greater impact on haemoglobin recovery than AL on days 28 and 42; this difference was significant.

Background/purpose Our previous study found significantly lower serum hematinic levels and higher serum homocysteine level as well as higher frequencies of serum hematinic deficiencies and hyperhomocysteinemia in oral leukoplakia (OL) patients than in healthy control subjects. This study evaluated whether carcinoembryonic antigen (CEA)-positive or squamous cell carcinoma-antigen (SCC–Ag)-positive OL patients had significantly lower serum hematinic levels and higher serum homocysteine level as well as significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients or healthy control subjects. Methods The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 184 OL patients including 85 CEA-positive, 99 CEA-negative, 25 SCC-Ag-positive, and 159 SCC-Ag-negative OL patients and in 184 age- and sex-matched healthy control subjects were measured and compared. Results We found that the 85 CEA-positive or 25 SCC-Ag-positive OL patients had a significantly lower mean serum folic acid level and a significantly higher mean serum homocysteine level as well as significantly higher frequencies of serum folic acid deficiency and hyperhomocysteinemia than 184 healthy control subjects. Moreover, the 25 SCC-Ag-positive OL patients had a significantly higher mean serum homocysteine level than the 159 SCC-Ag-negative OL patients. The 85 CEA-positive OL patients had a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than 99 CEA-negative OL patients (marginally significant, P = 0.060). Conclusion CEA-positive or SCC-Ag-positive OL patients tend to have a higher mean serum homocysteine level and a higher frequency of hyperhomocysteinemia than CEA-negative or SCC-Ag-negative OL patients, respectively.

OBJECTIVE To compare the effectiveness of erythropoietin alpha and erythropoietin beta in anemia management in the hemodialysis population. STUDY DESIGN Quasi-experimental study. PLACE AND DURATION OF STUDY Department of Nephrology, The Kidney Center Postgraduate Training Institute (TKC-PGTI), Karachi, from December 2019 to July 2020. METHODOLOGY All participants were initially started on erythropoietin alpha and then converted to erythropoietin beta after three months. The effectiveness of the erythropoietin alpha and erythropoietin beta was calculated on the basis of net change of mean hemoglobin and mean hematocrit level in the last four weeks on either erythropoietin therapy. RESULTS A total of 80 patients completed the study, in which 47 (58.8%) were males while 33 (41.3%) were females. The mean age was 59.7 ± 14.7 years. The net mean hemoglobin change during last 04 weeks was 0.19 ± 1.2 and 0.03 ± 1.0 for erythropoietin alpha and erythropoietin erythropoietin beta, respectively (p = 0.41). The net mean hematocrit change during the last four weeks was 0.45 ± 3.9 and 0.49 ± 3.7 for erythropoietin alpha and erythropoietin beta, respectively (p = 0.95). The mean weekly erythropoietin dosage per Kg body weight during the last four weeks was 177.6 ± 130.4 IU/Kg/week for erythropoietin alpha and 121.3 ± 69.6 IU/Kg/week for erythropoietin beta (p =

Objectives The majority of patients with head and neck cancer (HNC) come to the hospital at advanced stages. This research was conducted to determine the mortality, 2-year progression-free survival (PFS) and factors that influenced PFS of HNC patients. Methods A retrospective cohort study was conducted among locally advanced HNC patients who underwent chemoradiation for the first time at RSCM from January 2015 to December 2017. Data were retrieved through medical records. Laboratory data were taken 2–4 weeks prior and 2–4 weeks after chemoradiation. PFS observation started from the first day of chemoradiation until disease progression or death. PFS data were recorded in two groups: ≤ 2 years and > 2 years. The Chi-square test was used for bivariate analysis with the Fischer-exact test as an alternative. Variables will be further tested using multivariate logistic regression tests. Results Among 216 subjects, there were 103 (47.69%) patients who did not reach overall survival (OS) > 2 years. There were 108 (50%) patients who had PFS > 2 years. Based on the results of multivariate analysis, it was found that smoking, hemoglobin level ≤ 12 g/dl, ECOG (Eastern Cooperative Oncology Group) 1–2, and negative therapeutic response were associated with poor PFS. Hazard ratio (HR) for 2-year PFS for Brinkman index > 250 was 1.36 (95% CI 0.93–2.00; p = 0.02); HR for Hb ≤ 12 g/dl was 1.65 (95% CI 1.13–2.42; p = 0.01); HR for ECOG 1–2 was 4.05 (95% CI 1.49–11.00; p p Conclusion Mortality of HNC patients within 2 years is 47.69%, with a 2-year PFS reaching 50%. Cigarette smoking, low hemoglobin levels, poor performance status, and negative therapeutic response (non-responders) negatively affect the 2-year PFS.

Publisher Copyright: © 2021 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion. Background and Objectives: Deferral of blood donors due to low haemoglobin (Hb) is demotivating to donors, can be a sign for developing anaemia and incurs costs for blood establishments. The prediction of Hb deferral has been shown to be feasible in a number of studies based on demographic, Hb measurement and donation history data. The aim of this paper is to evaluate how state-of-the-art computational prediction tools can facilitate nationwide personalized donation intervals. Materials and Methods: Using donation history data from the last 20 years in Finland, FinDonor blood donor cohort data and blood service Biobank genotyping data, we built linear and non-linear predictors of Hb deferral. Based on financial data from the Finnish Red Cross Blood Service, we then estimated the economic impacts of deploying such predictors. Results: We discovered that while linear predictors generally predict Hb relatively well, they have difficulties in predicting low Hb values. Overall, we found that non-linear or linear predictors with or without genetic data performed only slightly better than a simple cutoff based on previous Hb. However, if any of our deferral prediction methods are used to assign temporary prolongations of donation intervals for females, then our calculations indicate cost savings while maintaining the blood supply. Conclusion: We find that even though the prediction accuracy is not very high, the actual use of any of our predictors in blood collection is still likely to bring benefits to blood donors and blood establishments alike.

Objective There is evidence that colorectal cancer screening using faecal haemoglobin is less effective in women than men. The faecal haemoglobin concentrations were therefore examined in women and men with screen-detected colorectal cancer. Setting Scottish Bowel Screening Programme, following the introduction of a faecal immunochemical test from November 2017, to March 2020. Methods Data were collated on faecal haemoglobin concentrations, pathological stage and anatomical site of the main lesion in participants who had colorectal cancer detected. The data in women and men were compared. Results For the faecal haemoglobin concentrations studied (>80 µg Hb/g faeces), the distributions indicated lower concentrations in women. Marked differences were found between women and men diagnosed with colorectal cancer. The median faecal haemoglobin concentration for women ( n = 720) was 408 µg Hb/g faeces compared to 473 µg Hb/g faeces for men ( n = 959) ( p = 0.004) and 50.6% of the results were >400 µg Hb/g faeces in women; in men, this was 57.8%. The difference in faecal haemoglobin concentrations in women and men became less statistically significant as stage advanced from stages I–IV. For right-sided, left-sided and rectal colorectal cancer, a similar gender difference persisted in all sites. Differences in faecal haemoglobin between the genders were significant for left-sided cancers and stage I and approached significance for rectal cancers and stage II, but all sites and stages showed lower median faecal haemoglobin concentrations for women. Conclusions To minimise gender inequalities, faecal immunochemical test-based colorectal cancer screening programmes should evaluate a strategy of using different faecal haemoglobin concentration thresholds in women and men.

BACKGROUND Up to 15% of people aged 60 and over are anemic, and the prevalence of anemia increases with age. In older men and women, anemia is associated with increases in the risk of death and all-cause hospitalization, poor functional capacity, quality of life, and depression. METHODS AND RESULTS We reviewed the literature describing anemia in aging populations, focusing on the specific diagnostic criteria of anemia and potential causes in older men and women. Even after extensive etiologic workup that involves careful medical history, physical examination, laboratory measurements, and additional studies such as bone marrow biopsy, anemia of aging is unexplained in up to 40% of older patients with anemia. As a result, treatment options remain limited. CONCLUSIONS The prevalence of unexplained anemia of aging (UAA; also called unexplained anemia of the elderly, UAE), its deleterious impacts on health, physical function, and quality of life, and the lack of effective treatment or therapy guidelines represent a compelling unmet clinical need. In this review and consensus document, we discuss the scope of the problem, possible causes of UAA, diagnostic criteria, and potential treatment options. Because even mild anemia is strongly linked to poor clinical outcomes, it should receive clinical attention rather than simply being considered a normal part of aging.

Despite a fingerstick hemoglobin requirement and 56-day minimum donation interval, repeat blood donation continues to cause and exacerbate iron deficiency.Using data from the REDS-II Donor Iron Status Evaluation study, we developed multiclass prediction models to estimate the competing risk of hemoglobin deferral and collecting blood from a donor with sufficient hemoglobin but low or absent underlying iron stores. We compared models developed with and without two biomarkers not routinely measured in most blood centers: ferritin and soluble transferrin receptor. We generated and analyzed "individual risk trajectories": estimates of how each donors' risk developed as a function of the time interval until their next donation attempt.With standard biomarkers, the top model had a multiclass area under the receiver operator characteristic curve (AUC) of 77.6% (95% CI [77.3%-77.8%]). With extra biomarkers, multiclass AUC increased to 82.8% (95% CI [82.5%-83.1%]). In the extra biomarkers model, ferritin was the single most important variable, followed by the donation interval. We identified three risk archetypes: "fast recoverers" (10% risk of any adverse outcome on post-donation day 56), "slow recoverers" (60% adverse outcome risk on day 56 that declines to35% by day 250), and "chronic high-risk" (85% risk of the adverse outcome on day 250).A longer donation interval reduced the estimated risk of iron-related adverse outcomesfor most donors, but risk remained high for some. Tailoring safeguards to individual risk estimates could reduce blood collections from donors with low or absent iron stores.

Background: In the VICTORIA trial (Vericiguat Global Study in Patients with Heart Failure with Reduced Ejection Fraction), anemia occurred more often in patients treated with vericiguat (7.6%) than with placebo (5.7%). We explored the association between vericiguat, randomization hemoglobin, development of anemia, and whether the benefit of vericiguat related to baseline hemoglobin. Methods: Anemia was defined as hemoglobin Results: At baseline, 1719 (35.7%) patients had World Health Organization anemia; median hemoglobin was 13.4 g/L (25th, 75th percentile: 12.1, 14.7 g/dL). At 16 weeks from randomization, 1643 patients had World Health Organization anemia (284 new for vericiguat and 219 for placebo), which occurred more often with vericiguat than placebo ( P Conclusions: Anemia was common at randomization and lower hemoglobin was associated with a greater frequency of clinical events. Although vericiguat modestly lowered hemoglobin by 16 weeks, this effect did not further progress nor was it related to the treatment benefit of vericiguat. Registration: URL: https://www.clinicaltrials.gov : Unique identifier: NCT02861534.

Population-based surveys commonly use point-of-care (POC) methods with capillary blood samples for estimating Hb concentrations; these estimates need to be validated by comparison with reference methods using venous blood. In a cross-sectional study in 748 participants (17–86 years, 708 women, Hb: 5·1 to 18·2 g/dl) from Hyderabad, India, we validated Hb measured from a pooled capillary blood sample by a POC autoanalyser (Horiba ABX Micros 60OT, Hb-C-AA) by comparison with venous blood Hb measured by two reference methods: POC autoanalyser (Hb-V-AA) and cyanmethemoglobin method (Hb-V-CM). These comparisons also allowed estimation of blood sample-related and equipment-related differences in the Hb estimates. We also conducted a longitudinal study in 426 participants (17–21 years) to measure differences in the Hb response to iron folate (IFA) treatment by the capillary blood POC method compared with the reference methods. In the cross-sectional study, Bland–Altman analyses showed trivial differences between source of blood (Hb-C-AA and Hb-V-AA; mean difference, limits of agreement: 0·1, −0·8 to 1·0 g/dl) and between analytical methods (Hb-V-AA and Hb-V-CM; mean difference, limits of agreement: < 0·1, −1·8 to 1·8 g/dl). Cross-sectional anaemia prevalence estimated using Hb-C-AA did not differ significantly from Hb-V-CM or Hb-V-AA. In the longitudinal study, the Hb increment in response to IFA intervention was not different when using Hb-C-AA (1·6 ± 1·7 g/dl) compared with Hb-V-AA (1·7 ± 1·7 g/dl) and Hb-V-CM (1·7 ± 1·7 g/dl). The pooled capillary blood–autoanalyzer method (Hb-C-AA) offers a practical and accurate way forward for POC screening of anaemia.

Objective To observe the perioperative free hemoglobin and haptoglobin levels and to assess their associations with the risk of postoperative acute kidney injury (pAKI) in adult patients undergoing valvular and aortic surgery requiring cardiopulmonary bypass (CPB). Design A single-center, prospective, observational study. Setting Public teaching hospital. Participants The study comprised 74 adult patients without chronic renal failure who underwent cardiovascular surgery requiring CPB from 2014 to 2020. Measurements and Main Results Perioperative free hemoglobin and haptoglobin levels during the study period were obtained from study participants. The primary outcome was pAKI defined by the Kidney Disease: Improving Global Outcomes criteria. Of the 74 patients in this study, pAKI occurred in 25 patients (33.8%). The free hemoglobin level began to increase after the initiation of CPB and reached a peak level at 30 minutes after weaning from CPB. It returned to the baseline level on postoperative day one. Haptoglobin levels were the highest after anesthesia induction and decreased continuously until postoperative day one. In the multivariate analysis, maximum free hemoglobin and minimum haptoglobin were associated independently with increased risk of pAKI (adjusted odds ratio 1.33 [95% confidence interval 1.12-1.58; p = 0.001] and 0.95 [95% confidence interval 0.91-1.00; p = 0.03], respectively). The free hemoglobin level began to have an independent association with pAKI at one hour after commencement of CPB, and the independent association disappeared at postoperative day one. Conclusions This study found that the perioperative increase of the free hemoglobin level and the decrease of the haptoglobin level had independent associations with the risk of pAKI.

The precise matching of blood flow to skeletal muscle during exercise remains an important area of investigation. Release of adenosine triphosphate (ATP) from red blood cells (RBCs) is postulated as a mediator of peripheral vascular tone in response to shear stress, hypoxia, and mechanical deformation. We tested the following hypotheses: 1) RBCs of different densities contain different quantities of ATP; 2) hypoxia is a stimulus for ATP release from RBCs; and 3) hypoxic ATP release from RBCs is related to RBC lysis. Human blood was drawn from male and female volunteers ( n = 11); the RBCs were isolated and washed. A Percoll gradient was used to separate RBCs based on cellular density. Density groups were then resuspended to 4% hematocrit and exposed to normoxia or hypoxia in a tonometer. Equilibrated samples were drawn and centrifuged; paired analyses of ATP (luminescence via a luciferase-catalyzed reaction) and hemolysis (Harboe spectrophotometric absorbance assay) were measured in the supernatant. ATP release was not different among low-density cells versus middle-density versus high-density cells. Similarly, hemoglobin (Hb) release was not different among the red blood cell subsets. No difference was found for either ATP release or Hb release following matched exposure to normoxic or hypoxic gas. The concentrations of ATP and Hb for all subsets combined were linearly correlated ( r = 0.59, P ≤ 0.001). With simultaneous probing for Hb and ATP in the supernatant of each sample, we conclude that ATP release from RBCs can be explained by hemolysis and that hypoxia per se does not stimulate either ATP release or Hb release from RBCs.

Background/Purpose: Lacto-vegetarians (LVs) tend to have vitamin B12 deficiency (B12D). This study assessed whether 140 female LVs, including 16 B12D/LVs and 124 non-B12D/LVs, had significantly higher frequencies of microcytosis, macrocytosis, and of blood hemoglobin (Hb), red blood cell (RBC), and serum vitamin B12 deficiencies than 140 healthy control subjects (HCSs). Methods: The complete blood count and serum vitamin B12 level in 140 female LVs and 140 female HCSs were measured and compared. Results: We found that 8.6%, 4.3%, 22.9%, 20.0%, and 11.4% of 140 LVs had microcytosis, macrocytosis, and blood Hb, RBC, and serum vitamin B12 deficiencies, respectively. The 140 LVs, 16 B12D/LVs, and 124 non-B12D/LVs had significantly higher frequencies of microcytosis as well as blood Hb and RBC deficiencies than 140 HCSs (all P-values

We aimed to investigate the resuscitative efficacy of hemoglobin vesicles (HbVs) as a red blood cell (RBC) substitute for the initial treatment of severe postpartum hemorrhage (PPH). Twenty-five pregnant rabbits underwent cesarean section; uncontrolled hemorrhage was induced by transecting the right uterine artery to establish a severe PPH model. During the first 30 min, all rabbits were administered 6% hydroxyethyl starch (HES) of an equivalent volume to the hemorrhage every 5 min. Thereafter, they received any of the following three isovolemic fluids for resuscitation every 5 min: RBCs with platelet-poor plasma (RBC/PPP) (n = 8), 6% HES (n = 7), or HbVs with 25% human serum albumin (n = 10). After surgical hemostasis at 60 min, survival was monitored until 12 h. No rabbits receiving only HES infusion survived beyond 6 h, whereas all rabbits receiving RBC/PPP transfusion survived. The rabbits receiving HbV infusion showed significantly higher mean arterial pressure and hemoglobin levels than the HES-receiving rabbits, and 8 of 10 rabbits survived for 6 h. The HbV group showed significantly higher survival than the HES group but worse survival than the RBC/PPP group. In conclusion, HbV infusion for severe PPH effectively prevents lethal hemorrhagic shock in a pregnant rabbit model.

Background Estimated plasma volume status (ePVS) has been reported that associated with poor prognosis in heart failure patients. However, no researchinvestigated the association of ePVS and prognosis in patients with acute myocardial infarction (AMI). Therefore, we aimed to determine the association between ePVS and in-hospital mortality in AMI patients. Methods and results We extracted AMI patients data from MIMIC-III database. A generalized additive model and logistic regression model were used to demonstrate the association between ePVS levels and in-hospital mortality in AMI patients. Kaplan–Meier survival analysis was used to pooled the in-hospital mortality between the various group. ROC curve analysis were used to assessed the discrimination of ePVS for predicting in-hospital mortality. 1534 eligible subjects (1004 males and 530 females) with an average age of 67.36 ± 0.36 years old were included in our study finally. 136 patients (73 males and 63 females) died in hospital, with the prevalence of in-hospital mortality was 8.9%. The result of the Kaplan–Meier analysis showed that the high-ePVS group (ePVS ≥ 5.28 mL/g) had significant lower survival possibility in-hospital admission compared with the low-ePVS group (ePVS P P P = 0.009), 1.04 (95% CI 1.01–1.07; P = 0.023), respectively. The ROC curve indicated that ePVS has acceptable discrimination for predicting in-hospital mortality. The AUC value was found to be 0.667 (95% CI 0.653–0.681). Conclusion Higher ePVS values, calculated simply from Duarte’s formula (based on hemoglobin/hematocrit) was associated with poor prognosis in AMI patients. EPVS is a predictor for predicting in-hospital mortality of AMI, and could help refine risk stratification.

Various types of hemoglobin (Hb)-based oxygen carriers (HBOCs) have been developed as red blood cell substitutes for treating blood loss when blood is not available. Among those HBOCs, glutaraldehyde polymerized Hbs have attracted significant attention due to their facile synthetic route, and ability to expand the blood volume and deliver oxygen. Hemopure®, Oxyglobin®, and PolyHeme® are the most well-known commercially developed glutaraldehyde polymerized Hbs. Unfortunately, only Oxyglobin® was approved by the FDA for veterinary use in the United States, while Hemopure® and PolyHeme® failed phase III clinical trials due to their ability to extravasate from the blood volume into the tissue space which facilitated nitric oxide scavenging and tissue deposition of iron, which elicited vasoconstriction, hypertension and oxidative tissue injury. Fortunately, conjugation of poly (ethylene glycol) (PEG) on the surface of Hb is capable of reducing the vasoactivity of Hb by creating a hydration layer surrounding the Hb molecule, which increases its hydrodynamic diameter and reduces tissue extravasation. Several commercial PEGylated Hbs (MP4®, Sanguinate®, Euro-PEG-Hb) have been developed for clinical use with a longer circulatory half-life and improved safety compared to Hb. However, all of these commercial products exhibited relatively high oxygen affinity compared to Hb, which limited their clinical use. To dually address the limitations of prior generations of polymerized and PEGylated Hbs, this current study describes the PEGylation of polymerized bovine Hb (PEG-PolybHb) in both the tense (T) and relaxed (R) quaternary state via thiol-maleimide chemistry to produce an HBOC with low or high oxygen affinity. The biophysical properties of PEG-PolybHb were measured and compared with those of commercial polymerized and PEGylated HBOCs. T-state PEG-PolybHb possessed higher hydrodynamic volume and P50 than previous generations of commercial PEGylated Hbs. Both T- and R-state PEG-PolybHb exhibited significantly lower haptoglobin binding rates than the precursor PolybHb, indicating potentially reduced clearance by CD163 + monocytes and macrophages. Thus, T-state PEG-PolybHb is expected to function as a promising HBOC due to its low oxygen affinity and enhanced stealth properties afforded by the PEG hydration shell.

Introduction: Lead is naturally available toxic heavy metal which is one of the main causes of environmental pollution and produces detrimental effects on health, particularly young children. Lead toxicity has become an emerging global burden of disease varying with the age, socio-economic status, occupation, industrialization, social customs and behaviours. The objective of this study was to find out the baseline blood lead level among children between 8-18 years. Methods: A descriptive study was conducted in Gokarneshwor Municipality, Kathmandu with a total of 160 children between 8-18 years of age from 2018 to 2019 after taking ethical approval from Research and Institutional Review Committee (Reference number: 17-074/075). Informed written consent was taken from the principal along with their respective parents and semi structured questionnaires were asked to students. Sample size was calculated and simple random sampling was done. The data was analyzed using Statistical Package for Social Science version 16. Point estimate at 95% Confidence Interval was calculated along with frequency and descriptive statistics. Results: The mean blood lead level of the children was 4.39±7.35 µg/dl. Mean hemoglobin being 12.63g/dl; out of 160 children 30 (18.75%) children had blood lead levels. Children with elevated blood lead level had mean haemoglobin level within normal range (13.05gm/dl), however out of 30 children, 8 (27%) had haemoglobin level below normal. Conclusions: Lead exposure in the children of urban area of Nepal is considerably high as compared to similar studies coducted in similar settings.

We analyzed the serum zinc levels of 37 patients with 40 phlegmon lesions. The mean serum zinc level was 52.1 ± 16.4 μg/dL. The serum zinc level was negatively correlated with the C-reactive protein (CRP) level (r = -0.66) and white blood cell (WBC) count (r = -0.56). It was also positively correlated with the serum levels of albumin, hemoglobin, and hematocrit (r = 0.57, 0.50, and 0.50, respectively). Patients with serum zinc levels of60 μg/dL had higher CRP levels and WBC counts (p 0.005 and p 0.05, respectively) and lower albumin, hemoglobin, and hematocrit levels (p 0.001, p 0.01, and p 0.01, respectively), and were more likely to be hospitalized (p 0.05) than those with serum zinc levels of ≥60 μg/dL. Patients with low serum zinc levels were given zinc tablets. Three of the seven patients who developed recurrent phlegmons did not develop any further lesions after taking zinc tablets for10 months. Of the remaining patients, one only developed a minimal lesion, and another two experienced recurrence twice but did not have any further lesions for 10 and 15 months, respectively. These findings indicate that in patients with phlegmons the serum zinc level is a suitable marker of the severity of infection, and zinc supplementation reduces the risk of further recurrence in patients whose lesions relapse.

Background Historically, the treatment of choice for anal cancer had been abdominoperineal resection (APR). Radical radiotherapy with concurrent 5-fluorouracil plus mitomycin C chemotherapy was later established as standard therapy, although with a failure rate of 20–30%. The aim of this study was to evaluate the outcomes after radical chemoradiotherapy (CRT), prognostic and predictive factors and patterns of failure. Patients and methods This study included 47 patients treated with radical CRT for patohistologicaly confirmed anal squamous cell carcinoma. Analysed haematological parameters included: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and haemoglobin level. The final logistic regression model included treatment break period. Tumour response was assessed at 24 weeks from CRT completion. Follow-up was performed every 3 months during the first two years, and every 6 months thereafter. Results A complete clinical response (CR) was detected in 30 patients (63.8%). Patients who did not achieve a 6-months CR and those who had a CR after 6 months but then relapsed were referred to surgical treatment. With combined CRT and surgical salvage treatment the CR rate was 80.9%. Patients with CR after 6 months had significantly longer disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS). A significant effect on the 6-month response was confirmed for PLR (p = 0.03). Conclusions Important prognostic factors associated with CR were baseline haemoglobin level and period of treatment interruptions. Potential haematological prognostic factors could be PLR and NLR, which can be routinely determined by low-cost and minimally invasive methods.

Background: Although conventional cardiopulmonary bypass (cCPB) is still the most widely used method in open heart surgery, methods such as retrograde autologous priming (RAP) are increasingly popular in terms of limiting hemodilution. Our hypothesis is that the use of the RAP method in aortic surgery may result in a limitation of hemodilution and a decrease in fHb levels. For this purpose, plasma free hemoglobin (fHb) levels were investigated in adult open aortic arch repair with axillary artery cannulation patients using cCPB and rRAP methods. Materials and Methods: In this study, a total of 36 patients undergoing aortic surgery using rRAP and standard cCPB were investigated. Measurements were performed at five time points: After induction of anesthesia, 5th minute of CPB, 10th minute of antegrade cerebral perfusion, 30th minute after declamping of aorta, and at sternum closure. Besides hemodynamic variables, arterial blood gas analysis and postoperative variables, patients were assessed for fHb levels. Results: The rRAP group had a significantly lower increase in fHb levels in T3, T4, and T5 time points, when compared to the cCPB group (p = 0.002, 0.047, 0.009, respectively). There was no significant difference between the rRAP and cCPB groups in other intraoperative, and postoperative variables. Also, it was observed that rRAP did not make a difference in terms of blood and blood product transfusion. Conclusion: In this study, in patients undergoing aortic surgery, a reduction in the increase of fHb was observed with the rRAP method which is a simple procedure that does not require high cost or advanced technology.

Abstract Background Detecting, treating and monitoring anaemia has a functional, social and economic impact on patients’ quality of life and the health system, since inadequate monitoring can lead to more accident & emergency visits and hospitalizations. The aim of this study is to evaluate the impact in the patient clinical outcomes of using haemoglobinometry to early detect anaemia in patients with chronic anaemia in primary care. Methods Randomized controlled trial Capillary haemoglobin will be measured using a haemoglobinometer on a monthly basis in the intervention group. In the control group, the protocol currently in force at the primary care centre will be followed and venous haemoglobin will be measured. Any cases of anaemia detected in either group will be referred to the transfusion circuit of the reference hospital. Discusion The results will shed light on the impact of the intervention on the volume of hospitalizations and accident & emergency (A&E) visits due to anaemia, as well as patients’ quality of life. Chronic and repeated bouts of anaemia are detected late, thus leading to decompensation in chronic diseases and, in turn, more A&E visits and hospitalizations. The intervention should improve these outcomes since treatment could be performed without delay. Improving response times would decrease decompensation in chronic diseases, as well as A&E visits and hospitalizations, and improve quality of life. The primary care nurse case manager will perform the intervention, which should improve existing fragmentation between different care levels. Trial registration NCT04757909. Registered 17 February 2021. Retrospectively registered.

Objective Myocardial injury after non-cardiac surgery (MINS) is an independent predictor of post-operative mortality in non-cardiac surgery patients and may increase health costs. Few data are available for MINS in vascular surgery patients, in general, and those undergoing fenestrated/branched endovascular aortic repairs (F/BEVAR), in particular. The incidence of MINS after F/BEVAR, the associated risk factors, and prognosis have not been determined. The aim of the present study was to help fill these knowledge gaps. Methods A single centre, retrospective study was carried out at a high volume F/BEVAR centre in a university hospital. Adult patients who underwent F/BEVAR between October 2010 and December 2018 were included. A high sensitivity troponin T (HsTnT) assay was performed daily in the first few post-operative days. MINS was defined as a HsTnT level ≥ 14 ng/L (MINS14) or ≥ 20 ng/L (MINS20). After assessment of the incidence of MINS, survival up to two years was estimated in a Kaplan–Meier analysis and the groups were compared according to MINS status. A secondary aim was to identify predictors of MINS. Results Of the 387 included patients, 240 (62.0%) had MINS14 and 166 (42.9%) had MINS20. In multivariable Cox models, both conditions were significantly associated with poor two year survival (MINS14: adjusted hazard ratio [aHR] 2.15, 95% confidence interval [CI] 1.10 – 4.19; MINS20: aHR 2.43, 95% CI 1.36 – 4.34). In a multivariable logistic regression, age, revised cardiac risk index, duration of surgery, pre-operative estimated glomerular filtration rate (eGFR), and haemoglobin level were independent predictors of MINS. Conclusion After F/BEVAR surgery, the incidence of MINS was particularly high, regardless of the definition considered (MINS14 or MINS20). MINS was significantly associated with poor two year survival. The modifiable predictors identified were duration of surgery, eGFR, and haemoglobin level.

The aim of the current research was to investigate the prognostic significance of pretreatment hemoglobin-to-red cell distribution width ratio (HRR) in patients with renal cell carcinoma (RCC). The neutrophil-to-lymphocyte ratio, systemic immune-inflammation index, lymphocyte-to-monocyte ratio (LMR) and HRR were analyzed retrospectively to assess their prognostic value using Kaplan-Meier curves and Cox regression analysis in 198 patients with RCC. High HRR (0.72) and high LMR (2.43) were found to be associated with longer progression-free survival and overall survival. A multivariate analysis identified International Metastatic Renal Cell Carcinoma Database Consortium prognostic score, tumor stage, node stage, LMR and HRR as independent prognostic factors for progression-free survival, as well as International Metastatic Renal Cell Carcinoma Database Consortium score, neutrophil-to-lymphocyte ratio and HRR for overall survival. HRR is a an independent prognostic parameter predicting the progression and survival of patients with RCC.Lay abstract Hemoglobin-to-red cell distribution width ratio (HRR) may be associated with lifespan in patients with cancer, as shown in previous studies of solid organ malignancy. The present study investigates the prognostic significance of pretreatment HRR in patients with renal cell carcinoma. A higher HRR was associated with longer survival in the present study, indicating the value of HRR as a predictor of survival and prognosis in renal cancer.