Improvement In Hematological Parameters Research Articles

“A Comprehensive Review of Anaemia Associated with Hypothyroidism”

Background: Thyroid hormones play a crucial role in erythropoiesis, both directly and indirectly, with reduced secretion potentially causing anaemia—a commonly overlooked symptom of hypothyroidism. By compiling existing data, discussing recent advancements, identifying root causes, and proposing potential treatment options, this work acknowledges the complexity of the issue and aims to serve as a foundational reference for those in the early stages of research or clinical practice. Methods: To comprehend the concept of this disease condition, a number of medical textbooks were consulted. Various search engines, such as PubMed, Google Scholar, Research Gate, Science Direct, Scopus, etc., were cited to explore the recent advancements and obtain data on the topic in question. Later, all the information and data gathered were organised into a review article. Conclusion: Anemia, often referred to as the “haematological mask” of hypothyroidism, can manifest even before hypothyroidism is clinically diagnosed. Hypothyroidism must be considered as a potential cause when confronted with refractory anemia, as its treatment is pivotal for achieving comprehensive and lasting improvements in haematological parameters.

Growth performance, meat quality and hematological parameters of broiler chickens fed safflower seed.

The aim of the current study was to determine the effects of dietary supplementation of safflower seed (SS) on the growth performance and hematological parameters of broiler birds along with the physicochemical, textural and sensory attributes of chicken meat. A total of 200 male chickens (7-days-old) were distributed into 5 groups (40 chickens in each) with 5 replicates of 8 chicks in a 42-day experiment. Each group was allocated to one of 5 dietary treatments, i.e., 0, 2.5, 5, 7.5, and 10% SS. The experimental diets were formulated for starter (7 to 21 days) and finisher (22 to 42 days) phases. Inclusion of SS in the diet improved growth performances in treatment groups between 7 and 42 days. The highest and lowest body weights were observed at the 5% SS and 0% SS levels, respectively. The physicochemical attributes of breast and thigh meat were found (P > 0.05) except for crude fat. The crude fat was significantly (P < 0.05) increased with increasing levels of SS in the diet. The inclusion of SS in the diet did not negatively impact the textural properties, i.e., hardness, cohesiveness, springiness, gumminess, chewiness, and shear force of breast and thigh meat. There was no significant difference in the sensory parameters of cooked chicken meat with increasing levels of SS in the diet. The results demonstrated a significant (P < 0.01) improvement in hematological parameters in the blood samples of broiler chickens fed diet supplemented with various levels of SS for five weeks. These findings suggest that, SS may be used as an oil seed for broiler chicken feed.

Long-Term Outcomes of Disease Modifying Therapies in Gaucher Disease.

To study clinical response to treatment with enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) in a cohort of Gaucher disease. Retrospective data of 8 patients of Gaucher disease was compiled. The treatment included all three currently available enzyme replacement therapies as well as substrate reduction therapy with Eliglustat. The relevant blood investigations were done in follow-up visits. The assessment of the effects of long-term treatment over varying periods up to 13 y was done with various issues related to the course of therapy documented. Improvement in hematological parameters was seen in all patients. Reduction of spleen size occurred in 7 of 8 patients (87.5%). One patient had 2 successful pregnancies while on therapy. A distinct patient with type 3 Gaucher disease developed complication in the form of Gaucheroma within the spleen. Awareness about the disease and the efficacy of the therapies amongst pediatricians will help in early diagnosis and better outcomes. The available therapies have changed the outcome of the patients and improved the quality of life in patients with Gaucher disease. The data of Indian patients is important at this juncture when under Rare Disease Policy, government funding has become available for ERT for Gaucher disease patients in India.

Clinical effectiveness of ferric carboxymaltose (iv) versus iron sucrose (iv) in treatment of iron deficiency anaemia in pregnancy: A systematic review and meta-analysis.

Iron deficiency anaemia (IDA) during pregnancy is treated with oral and parenteral iron. The objective of this review was to compare the clinical effectiveness, safety, pregnancy and neonatal outcomes of intravenous (iv) ferric carboxymaltose (FCM) and iv iron sucrose (IS) in treating IDA in pregnancy. The Department of Health Research funded this study. PubMed, Cochrane Library, EMBASE and Scopus were searched to include studies published till November 2022. The protocol was registered in PROSPERO (CRD42022306092). Pregnant women (15-49 yr) in second and third trimesters, diagnosed with moderate-to-severe iron deficiency anaemia, treated with either of the drugs were included. The included studies were critically assessed using appropriate tools. We conducted a qualitative synthesis of the studies and meta-analysis for improvement in haematological parameters and incidence of adverse events. A total of 18 studies were included. The risk of bias was low to moderate. A rise in haemoglobin up to four weeks was higher with FCM than IS by 0.57 (0.24, 0.9) g/dl. Intravenous FCM is associated with fewer adverse events than IS [pooled odds ratio: 0.5 (0.32, 0.79)]. The included studies had limited evidence on pregnancy and neonatal outcomes after iv iron treatment. Intravenous FCM is effective and safer than intravenous IS in terms of haematological parameters, in treating IDA in pregnancy. Further research is required on the effects of iv FCM and iv IS on the pregnancy and neonatal outcomes when used for treating IDA in pregnancy.

Использование воды с электрохимически регулируемым окислительно-восстановительным потенциалом при содержании осетровых рыб в установках замкнутого водоснабжения

The active interest of modern researchers in studying the structure of water, its unique biological and physical properties is due to the peculiarities of structured water: it does not contain impurities, and its properties are similar to biological fluids that are part of animal and plant cells. The molecules of structured water are not scattered randomly, but are connected to each other in a single structure. Negatively charged structured water has a biostimulating effect on fish, which manifests itself in increasing survival, fertilization of eggs, accelerating the growth rate of juveniles, reducing the load of pathogenic microflora on the body of aquatic organisms. The cultivation of sturgeons was carried out at the optimal water temperature for their growth – 22 °C, the oxygen content did not exceed 8.0 mg/l. Special attention was paid to pH due to its shift towards the alkaline reaction of the medium in water with negative (lowering) values of the redox potential (RP). During experiments on sturgeons, the positive effect of water with negative RP on the body of Russian sturgeon × Lena sturgeon (RS × LS) hybrids was established, which manifested itself in an increase in fish-breeding and biological indicators of cultivation. The absolute increase in individuals kept in water with controlled RP was 26% higher compared to the control. The average daily growth rate was also higher in individuals of the experimental group, it was 0.72%. It was noted that when fish were kept in water with electrochemically regulated RP, an improvement in hematological parameters was observed (hemoglobin – 73.3 g/l, total protein – 22.7 g/l), as well as a decrease in the rate of erythrocyte sedimentation to 2.5 mm/h, which indicates a favorable effect of structured water on the physiological state of aquaculture facilities.

A case study on Ayurvedic management on Kamala w.s.r. to Hepatitis E Virus

Hepatitis is defined as liver inflammation that can be caused on by a number of conditions, including prolonged drug use, heavy alcohol consumption, autoimmune conditions, and exposure to toxins. The term "viral hepatitis" describes the most common type of hepatitis, which is caused by an infection with a virus. In this case, report effect of Ayurveda intervention in HEV is reported. A 55-year, old non-alcoholic, married male patient from an urban area, presented with yellowish discolouration of sclera, urine, upper and lower extremities, reduced appetite, nausea, fatigue with generalized weakness and experiencing upper abdominal pain to the National Institute of Ayurveda Hospital, Jaipur, Rajasthan. On examination, icterus was present, pitting edema present on both lower legs. Hematological examination revealed altered total bilirubin, SGOT, SGPT, Triglycerides, ESR, CRP. Also, sonographic examination revealed a mild hepatomegaly in the patient. The total duration of the treatment was 2 months. The patient was assessed for improvement in hematological parameters, viral markers, and signs and symptoms. after two months, significant improvement was observed in signs and symptoms, and all altered hematological parameters, and viral markers were within normal limits. Hence, presenting this case is evidence to demonstrate the effectiveness of two months of Ayurvedic treatment in managing HEV. The total duration of the treatment was 60 days.

The contribution of Coriandrum sativum in enhancing Oreochromis niloticus rearing at sub-optimal temperatures: effect on growth, health status, survival rate, and resistance to Aeromons Veronii

This study (60 days) was conducted to investigate the ability of diet enriched with Coriandrum sativum powder or its extract to protect Oreochromis niloticus health and survivability at suboptimal temperature (21 ℃). One hundred and twenty (33.14 ± 0.5 g) were divided into four groups; each group has three replicates.. The first control group fed on a basal diet. Second and third groups fed on diet enriched with 30 mg/kg coriander seed powder (CP) and coriander seed ethanolic extract (CE), respectively. The fourth group (OT) fed on diet enriched with 500 mg oxytetracycline/kg diet. The results revealed that CE exhibited a considerable improvement in hematological parameters, hepatic-renal functions, antioxidant status, and immunological markers as well as remarkably increased resistance against Aeromonas veronii. It could be concluded that feeding tilapia CE enriched diet at 30 mg/kg is a recommended strategy to enhance tilapia health and resistance to A. veronii infection reared at 21 ℃.

Ivosidenib for Patients with Clonal Cytopenia of Undetermined Significance and Mutations in IDH1

Background Myeloid neoplasms (MN), including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), are hematologic malignancies that are highly resistant to therapy and confer a poor prognosis. Recent studies have revealed that hematopoietic stem cells and progenitor cells carrying preleukemic mutations, defined as clonal hematopoiesis (CH), are the cells of origin in MN. CH can occur many years before the diagnosis of MN. Multiple mutations, mutations with a high variant allele frequency (VAF), and mutations in TP53, spliceosome genes, and isocitrate dehydrogenase 1/2 ( IDH1/2) have been identified as high-risk features for CH progression to MN. Individuals with cytopenias who harbor acquired mutations in their blood yet do not meet criteria for hematologic malignancy, an entity called clonal cytopenia of undetermined significance (CCUS), have an even higher risk of developing MN (estimated at 95% over 10 years of follow-up). Thus, despite being almost inevitably destined for progression to malignancy, there are no established preventative therapies for patients with CCUS. The IDH1 inhibitor ivosidenib has been extensively evaluated in clinical studies and has been shown to effectively inhibit the gain-of-function activity of the mutated protein. Clinical data has shown that ivosidenib is safe and well-tolerated with excellent response rates even in patients with relapsed or refractory AML. Individuals with lower co-mutational burden are more likely to have a clinical response and achieve molecular remission with ivosidenib. Since CCUS is characterized by a lower mutation burden compared to AML or MDS, we hypothesize that the use of ivosidenib in IDH1-mutant CCUS will result in a higher and more prolonged clinical response. Study Design and Methods NCT05030441 is a decentralized open label, multicenter pilot study exploring the efficacy of ivosidenib in patients with IDH1-mutant CCUS. The study is offered as a decentralized trial (DCT) where patients across the US can participate with study procedures occurring in the patient's home using telemedicine, mobile phlebotomy services and with local providers. By reducing barriers to trial participation, we expect that the DCT design will improve accessibility for this rare patient population. This represents an important step toward making personalized medicine available to a socio-economically diverse patient population and enables rare mutations to be studied at scale. Patients with CCUS harboring the IDH1 R132 mutation are considered eligible if they do not have any concurrent active malignancy requiring treatment. Patients must have unexplained cytopenia lasting ≥6 months, defined as hemoglobin &amp;lt;10 g/dL, absolute neutrophil count &amp;lt;1.8 × 10 9/L and platelets &amp;lt;100 × 10 9/L, as well as adequate baseline organ function including renal and liver function, as per the National Institutes of Health Common Terminology Criteria for Adverse Events (NCI CTCAE) grading. Recruitment and data collection will be coordinated with local providers for patients that enroll remotely. A total of 15 patients will be accrued to receive ivosidenib 500 mg daily for up to 18 cycles. The primary endpoint is rate of improvement in hematologic parameters using specific cutoffs for erythroid, platelet and neutrophil responses based on the MDS response criteria. The study will be considered positive if at least 6 out of the 15 patients have a hematologic improvement. Secondary endpoints include change in mutant IDH1 VAF, measured at baseline and every 3 cycles on peripheral blood samples, safety of ivosidenib, and AML/MDS-free survival which will be evaluated by descriptive statistics and Kaplan-Meier methodology. Enrollment opened in one US center and by decentralized structure in April 2022, with 3 patients accrued, and is expected to open in other US centers in 2023. If the study endpoints are met, our aim is to expand to a larger population with the goal of determining whether ivosidenib can prevent the development of hematologic malignancy in patients with IDH1-mutant CCUS.

Cytokine and Mutation Profiling Reveal Patterns of Complete Remission Rates with Lenzilumab Combination Therapy in Chronic Myelomonocytic Leukemia

Introduction: Chronic myelomonocytic leukemia (CMML) is characterized by accumulation of classical CD14+CD16- inflammatory monocytes driven in part by hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), a pro-inflammatory cytokine. Standard of care in CMML includes hypomethylating agents such as azacytidine (AZA), with complete response (CR) rates of 16-21% 1,2 and no reliable biomarkers that predict response. The complete pro-inflammatory profile of CMML is unknown and no treatment addresses the hematologic aberrations of CMML. Lenzilumab (LENZ; Humanigen, Inc., Short Hills, NJ) is a proprietary Humaneered ® first-in-class monoclonal antibody with best-in-class off-rate and affinity that neutralizes GM-CSF. The interim analysis of the PREcision Approach to CHronic Myelomonocytic Leukemia (PREACH-M; ACTRN12621000223831) trial showed LENZ/AZA treatment in 11 subjects with RAS-pathway ( NRAS/ KRAS/ CBL) mutations resulted in 8 subjects with complete response or optimal marrow response and improvements in hematological parameters. This report describes the cytokine profiles and systemic C-reactive protein levels of these subjects. Methods: PREACH-M is a Phase 2/3 non-randomized, open-label trial in 72 subjects, aged at least 18 years, with newly diagnosed CMML based on the WHO 2016 criteria; and RAS-pathway mutations at a variant allele frequency ≥3%. Subjects received 24 cycles (every 28 days) of AZA (SC; 75 mg/m 2 for 7 days) and LENZ (IV; 552 mg; d1 &amp; d15 of cycle 1 and d1 only for all subsequent cycles). Subjects without RAS-pathway mutations received the same AZA regimen and sodium ascorbate (IV; 30g for 7 days (15g for 1st dose only; 30g thereafter if no evidence of tumor lysis syndrome); PO; 1.1g on all other days). Cytokine profiling from bone marrow plasma was performed after 4,7,12 and 24 months using Milliplex Human Cytokine/Chemokine Magnetic bead panel and compared with 24 age-matched healthy subjects. Unsupervised hierarchical clustering with Ward's method sought distinct CMML patterns based on cytokine expression. C-reactive protein (CRP) was determined from blood samples using a routine assay. Variant allele frequencies were determined from bone marrow mononuclear cells using a 41-myeloid panel using Illumina Hi-Seq with a depth of 1000x. Results: As of July 2023, 15 subjects were enrolled in the LENZ/AZA arm (8 females, 7 males with mean age 69; mean white cell count, 21x10 9/L; mean Hb, 121 g/L, mean platelet count; 74x10 9/L, mean blast count, 10.1%). CRP decreased from a median of 5.6 at baseline to 2.1 mg/L after 6 months of LENZ/AZA (P=0.02). GM-CSF and other pro-inflammatory cytokines were increased in CMML bone marrow plasma compared with healthy subjects. Hierarchical clustering of all subjects revealed 2 patterns of CMML, distinct from healthy subjects. Cluster “INNATE-1” was comprised of medium increases in inflammatory cytokines associated with innate immune response and M1 macrophage activation (IFN-g, IL-1b, TNFa, IL-12p70, IL-12p40, IL-17, Fractalkine, MCP-3). Cluster “INNATE-2” was associated with extreme increases of these cytokines. The mean pro-inflammatory innate immune score (sum of z-scores) was 20-fold greater in INNATE-2 compared with INNATE-1 ( P=0.055). Somatic mutations SRSF2, WT1, PHF6 were enriched in INNATE-2. All patients (5/5) in INNATE-1 showed 100% response (CR or optimal marrow response resulting in &amp;lt;5% blasts) to AZA/LENZ. Two subjects (2/6) in INNATE-2 demonstrated partial responses or haematological improvement thus far. Conclusion: CMML is a disorder of profound innate immune activation, driven by GM-CSF and other pro-inflammatory cytokines. Early treatment with LENZ/AZA, a precision immunotherapeutic approach, leads to a) efficacy in INNATE-1 that exceeds historical CR rates for hypomethylating agents 1,2; and b) evolving efficacy in INNATE-2, in which pro-inflammatory activity is more robust. 1. Xu Y, Guo R, Miao M, Zhang G, Lan J, Jin J. Real-world data on efficacy and safety of azacitidine therapy in chronic myelomonocytic leukemia in China: results from a multicenter, retrospective study. Invest New Drugs 2022;40(5):1117-1124. DOI: 10.1007/s10637-022-01283-x. 2. Zheng X, Lv L, Li X, Jiang E. Efficacy and Safety of Hypomethylating Agents in Chronic Myelomonocytic Leukemia: A Single-Arm Meta-analysis. Glob Med Genet 2022;9(2):141-151. DOI: 10.1055/s-0042-1744157.

Phytochemical screening, in vitro and in vivo effects of an aqueous extract of the bark of Combretum glutinosum Perr ex DC. (Combretaceae) on gastrointestinal strongyles

IntroductionPlants remain an inexhaustible source of medicines for the treatment of various diseases. The aim of this study was to evaluate the anthelmintic activity of the aqueous extract of Combretum glutinosum bark on adult gastrointestinal strongyle worms. MethodsIn vitro, the extract was contacted with worms at various doses. In vivo, 25 sheep were divided into five batches of 5 animals, with one batch untreated, one batch treated with albendazole and three batches treated with the extract at three different doses. The body weight of the animals, the number of eggs per gram of faeces and haematological parameters were used to assess the efficacy of the extract. ResultsIn vitro, the extract appeared to inhibit the motility of adult Haemonchus contortus worms more than Trichostrongylus colubriformis (P < 0.05). In vivo, a significant reduction in the faecal excretion rate was observed in batches of animals treated with the drug and those treated with the extract, compared with the untreated control. Similarly, an increase in animal weight and an improvement in haematological parameters were observed in the treated batches after experimentation. The chemical profile of the extract revealed the presence of various chemical groups suspected of being responsible for its anthelmintic properties. ConclusionTreatment at a dose of 100 mg/kg body weight appeared to be more active in reducing the number of eggs per gram of faeces and could therefore be recommended for the formulation of an improved traditional medicines with anthelmintic properties.

Black cardamom (Amomum subulatum) extract improves growth potential, antioxidant status, immune parameters and response to crowding stress in Catla catla.

Natural herbs are excellent alternatives to synthetic compounds to enhance the growth performance and health status of fish. This study was conducted to evaluate the efficacy of black cardamom (Amomum subulatum) extract (BCE) as an herbal supplement in improving the growth, antioxidant status, haematology, and serum biochemistry of Catla catla. The acclimatized fish (N = 900; average initial weight = 14.44 ± 0.33 g) were allocated into five groups (60 fish/group in triplicate) in hapas (4 × 2 × 2.5 ft) and provided with feed containing 0 (control), 0.5, 1, 2and 4 g/kg BCE for 90 days before being subjected to 8 days of crowding stress. After 90 days, significantly higher feed utilization and growth were observed in all BCE-fed treatments compared to the control; however, the maximum values of these parameters were noted in the 2 g/kg BCE-fed treatment. Moreover, the BCE-fed groups exhibited a significant increase in antioxidant indices (glutathione peroxidase, superoxide dismutaseand catalase), with a significant reduction in malondialdehyde levels, indicating a higher antioxidant capacity compared to the control. Significant improvements in haematological parameters, such as an increase in haematocrit, haemoglobinand red blood cells and a decrease in white blood cells, were observed in BCE-fed treatments compared to the control. Furthermore, BCE-fed groups showed a significant decrease in serum glucose, cortisoland triglycerides, while total protein, globulinand albumin levels were significantly higher compared with the control. During the feeding trial of 90 days, no mortality was observed; however, the lowest cumulative mortality was noted in the 2 g/kg BCE group after crowding stress of 8 days. In conclusion, the use of BCE in feed can enhance the growth performance, antioxidant status, haematology, and serum biochemistry of C. catla and improve the resistance against crowding stress. The optimum levels of BCE for C. catla were estimated based on weight gain % (1.78 g/kg; R2 = 0.97), feed conversion ratio (1.65 g/kg; R2 = 0.98), MDA content (1.66 g/kg; R2 = 0.93) and serum lysozyme activity (1.72 g/kg; R2 = 1) using broken-line regression analysis.

Iron Deficiency Anemia Presenting With Pancytopenia: A Study From India.

Iron deficiency anemia (IDA) is the most common cause of anemia worldwide. IDA is commonly associated with thrombocytosis and normal or slightly decreased leukocyte count. Sometimes it can present with thrombocytopenia, but rarely present with pancytopenia. Here we are presenting six cases of severe iron deficiency presenting with pancytopenia, which responded to iron replenishment. This 12-month observational study was conducted in the Department of General Medicine at a tertiary care Centre in India. All cases of pancytopenia (after exclusion of other causes) with IDA were included. IDA was established with the help of a complete blood count (CBC), peripheral smear examination, serum iron studies, and serum ferritin. Results: In our study, CBC at four weeks later of iron transfusion without other supplementation showed significant improvement in hematological parameters. Severeiron deficiency is a reversible etiology of pancytopenia. It should be kept as a differential diagnosis of pancytopeniaif common causes of pancytopenia are ruledout.

The Effect of Lactoferrin Supplementation on Iron level and Haematological Parameters after Sleeve Gastrectomy

Abstract Background Sleeve gastrectomy (SG) is one of the most effective bariatric surgery methods of treatment for obesity. It can cause nutritional deficiencies and lead to anemia at the same time. Aim and objectives To evaluate the effect of lactoferrin supplementation on iron level and haematological parameters after three months of supplementations for sleeve gastrectomy patients. Subjects and Methods This study is a randomized control clinical study, Forty patients after sleeve gastrectomy divided into two groups as follows: (Group 1): 20 cases received ferrous sulphate capsule once daily for 3 consecutive months, (Group 2): 20 cases received lactoferrin sachet twice daily for 3 consecutive months with ferrous sulfate capsule once daily. Result There is a significant increase in hemoglobin, HCT, and RBCs after 3-months follow up on ferrous sulfate supplementation. Meanwhile, there is a significant decrease in serum ferritin after 3 months follow up. However, the improvement in hematological parameters was more significant in the group of lactoferrin with ferrous sulfate. Conclusion Oral lactoferrin was better tolerated and more acceptable in combination with oral iron with higher increase in hematological parameters when compared to oral iron therapy alone over three-months treatment.

Use of Ambroxol as Therapy for Gaucher Disease

Ambroxol was identified as an enhancer of stability and residual activity of several misfolded glucocerebrosidase variants in 2009. To assess hematologic and visceral outcomes, biomarker changes, and safety of ambroxol therapy for patients with Gaucher disease (GD) without disease-specific treatment. Patients with GD who could not afford enzyme replacement therapy were enrolled and received oral ambroxol from May 6, 2015, to November 9, 2022, at Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China. Thirty-two patients with GD (29 with GD type 1, 2 with GD type 3, and 1 with GD intermediate types 2-3) were enrolled. Of those, 28 patients were followed up for longer than 6 months; 4 were excluded due to loss of follow-up. Data analyses were performed from May 2015 to November 2022. An escalating dose of oral ambroxol (mean [SD] dose, 12.7 [3.9] mg/kg/d). Patients with GD receiving ambroxol were followed up in a genetic metabolism center. Biomarkers of chitotriosidase activity and glucosylsphingosine level, liver and spleen volumes, and hematologic parameters were measured at baseline and various time points throughout the ambroxol treatment. A total of 28 patients (mean [SD] age, 16.9 [15.3] years; 15 male patients [53.6%]) received ambroxol for a mean (SD) duration of 2.6 (1.7) years. Two patients with severe symptoms at baseline experienced deterioration of hematologic parameters and biomarkers and were deemed nonresponders; clinical response was observed in the other 26 patients. After 2.6 years of ambroxol treatment, the mean (SD) hemoglobin concentration improved from 10.4 (1.7) to 11.9 (1.7) g/dL (mean [SD], 1.6 [1.7] g/dL; 95% CI, 0.8-2.3 g/dL; P < .001), and the mean (SD) platelet count improved from 69 (25) to 78 (30) × 103/µL (mean [SD], 9 [22] × 103/µL; 95% CI, -2 to 19 × 103/µL; P = .09). The mean (SD) spleen volume decreased from 17.47 (7.18) to 12.31 (4.71) multiples of normal (MN) (mean [SD], -5.16 [5.44] MN; 95% CI, -10.19 to -0.13; P = .04), and the mean (SD) liver volume decreased from 1.90 (0.44) to 1.50 (0.53) MN (mean [SD], -0.39 [0.42] MN; 95% CI, -0.75 to -0.04; P = .03). Biomarker median percentage changes from baseline were -43.1% for chitotriosidase activity (from 14 598 [range, 3849-29 628] to 8312 [range, 1831-16 842] nmol/mL/h; z = -3.413; P = .001) and -34.1% for glucosylsphingosine level (from 251.3 [range, 73.6-944.2] to 165.7 [range, 21.3-764.8] ng/mL; z = -2.756; P = .006). Patients were divided into subgroups according to age when initiating treatment; those who received treatment at a younger age (mean [SD] age, 6.3 [2.7] years) experienced more rapid improvements: hemoglobin concentration increased by 16.5% (from 10.3 [1.5] to 12.0 [1.5] g/dL; mean [SD] change, 1.6 [1.6] g/dL; 95% CI, 0.7-2.5 g/dL; P = .002), and platelet count increased by 12.0% (from 75 [24] to 84 [33] × 103/µL; mean [SD] change, 9 [26] × 103/µL; 95% CI, -5 to 24 × 103/µL; P = .17); whereas chitotriosidase activity decreased by 64.0% (from 15 710 [range, 4092-28 422] to 5658 [range, 1146-16 843] nmol/mL/h; z = -2.803; P = .005), and glucosylsphingosine level decreased by 47.3% (from 248.5 [range, 122.8-674.9] to 131.0 [range, 41.1-448.5] ng/mL; z = -2.385; P = .02). Three of the 28 patients experienced mild and transient adverse events. In this case series of ambroxol repurposing among patients with GD, long-term treatment with ambroxol was safe and associated with patient improvement. Improvements in hematologic parameters, visceral volumes, and plasma biomarkers were larger among patients with relatively mild symptoms of GD and patients who received initial treatment at younger ages.

Aronia melanocarpa (Michx.) Elliott 1821 Extract Has Moderate Ameliorative Influence on Biochemical and Hematological Parameters in Gentamicin-Induced Nephropathy in Wistar Rats.

Gentamicin (GM) is an aminoglycoside antibiotic used to treat bacterial infections. Nephrotoxicity refers to the impairments of the kidneys caused by the use of GM and can result in decreased kidney function and in severe cases, kidney failure. Aronia melanocarpa extract (AME), also known as the black chokeberry, has been used for its protective effects on the kidneys. AME concentration of 3.38mg/kg (max antioxidant activity in vitro) was used to determine its effectiveness against induced nephropathy during 30days. GM treatment caused significant hypoalbuminemia and high values of globulins, creatinine, and urea compared to the control group. GM application lead to hemolysis occurrence, echinocytosis, and platelets aggregation. Significantly high values of segmented neutrophils and low values of non-segmented neutrophils were recorded in the blood of rats treated with chokeberry extract (AME). In the pre-treatment (AME + GM), severe hypochromic anemia and a significant improvement in hematological parameters, as well as a reduction of anemia in the post-treatment (GM + AME), were noted. Post-treatment AME also significantly regulates urea and creatinine values. Statistically significantly low hemoglobin values were found in all groups treated with AME. Current study suggests that compounds in the AME have a moderate beneficial effect against renal injury and anti-inflammatory properties that may help protect the kidneys from injury caused by GM.

Leveraging mathematical modeling to analyze nonadherence for hydroxyurea therapy in sickle cell disease.

Nonadherence is common in individuals with sickle cell disease (SCD) on hydroxyurea therapy and can be observed with waning improvements in hematologic parameters or biomarkers like mean cell volume and fetal hemoglobin level over time. We modeled the impact of hydroxyurea nonadherence on longitudinal biomarker profiles. We estimated the potential nonadherent days in individuals exhibiting a drop in biomarker levels by modifying the dosing profile using a probabilistic approach. Incorporating additional nonadherence using our approach besides existing ones in the dosing profile improves the model fits. We also studied how different patterns in adherence give rise to various physiological profiles of biomarkers. The key finding is consecutive days of nonadherence are less favorable than when nonadherence is interspersed. These findings improve our understanding of nonadherence and how appropriate intervention strategies can be applied for individuals with SCD susceptible to the severe impacts of nonadherence.

TO STUDY THE EFFECTS OF DIFFERENT TIMING OF DELAYED CORD CLAMPING ALONG WITH MILKING ON HAEMATOLOGICAL PARAMETERS IN NEWBORNS - A RANDOMIZED CONTROL TRIAL

Objectives: Evaluation of the hematological parameter in newborn by delayed cord clamping at 60 s and at 180 s. Comparison of the improvement in hematological parameters, that is, hemoglobin and serum ferritin in newborn by both methods. Methods: This was randomized, controlled, and comparative study conducted during April 2021 to February 2022 at the Department of Obstetrics and Gynaecology, SMS Medical College, Jaipur. The study included sample size of 60 cases (30 cases in each group). 60 cases were randomly allocated to either 60 s (Group A) or 180 s (Group B) groups of delayed cord clamping. The study included all singleton pregnant women &gt;34 weeks of gestational age. Results: Mean hemoglobin±standard deviation of neonate at birth for Group A was13.53±0.56 g/dL and for Group B it was 13.85±0.55 g/dL. Mean hemoglobin ± standard deviation at 6 month for Group A was 13.19±0.53 g/dL and for Group B was 13.53±0.55 g/dL. Mean serum ferritin±standard deviation of infant at for Group A was 12.46±0.45% and for Group B was 12.86±0.55%. Conclusion: Neonatal hemoglobin and serum ferritin were significantly higher in180 s delayed cord clamping as compared to 60 s delayed cord clamping group.

Effectiveness of iron-based phosphate binders in reduction of hyperphosphataemia in chronic kidney disease patients

Background: Ferric citrate is novel iron-based phosphate-binding drug for management of hyperphosphataemia and iron-deficiency anaemia in chronic kidney disease (CKD) patients. Objectives: To evaluate impact of ferric citrate therapy on reduction of phosphate levels and improvement in haematological parameters in CKD stages 3-5. Methods: This analytical, observational study was conducted at Kathmandu Medical College Teaching Hospital from 2020 July-December after ethical clearance using convenience sampling method. Non-dialysis dependent patients at CKD stages 3-5, having hyperphosphataemia (serum phosphate &gt;=4.6mg/dL) and anaemia (serum haemoglobin &lt;12 gm%, transferrin saturation &lt;=30%, ferritin &lt;=300ng/mL) were administered with 2gm twice daily dose of ferric citrate for 12 weeks and evaluated on outcomes in terms of reduction in serum phosphate levels and improvement in haematological parameters as study endpoints. Data were entered in Microsoft Excel and analysed in SPSS v.25. Significance level was set at p &lt;0.05. Results: Of 84 study participants, majority had CKD stage 4 (46, 54.76%). A significant reduction (p &lt;0.001) in mean serum phosphate levels of 6.21 ± 1.062 mg/dL from baseline to 4.89 ± 1.100 mg/dL in 12-weeks was observed. Patients with CKD stages 3, 4, and 5 had mean reduction of 1.67 (p = 0.005), 1.40 (p &lt;0.001), and 1.04 mg/dL (p = 0.002) of serum Phosphate level respectively. Significant (p &lt;0.001) improvements in hemoglobin level, serum iron, ferritin, total iron binding capacity, and transferrin saturation were reported. Conclusion: Ferric citrate is effective and well-tolerated phosphate-binder to improve hyperphosphataemia and iron deficiency anaemia in non-dialysis CKD stage 3, 4, and 5.

Long-Term Efficacy and Safety of L-Glutamine in Preventing Sickle Cell Disease-Related Acute Complications and Hemolysis in Pediatric and Adult Patients: A Real-World Observational Study

Introduction: L-glutamine plays an important role in regulating oxidative stress, one of the key contributors to sickle cell disease pathophysiology. An earlier 48-week Phase 3 study conducted in the United States demonstrated significant reductions in acute complications associated with sickle cell disease, such as vaso-occlusive crises (VOCs) and acute chest syndrome (ACS) in patients on L-glutamine therapy compared to those on placebo (Niihara et al., 2018). This study also showed a significantly fewer number of hospitalizations and hospitalization days for those treated with L-glutamine. Our current real-world observational study is the first to report long term evaluation (120 weeks) of efficacy and safety of L-glutamine (Endari®) therapy in patients living with sickle cell disease in Qatar and French Guiana. Methods: Nineteen patients (10 pediatric and 9 adults), 63% on hydroxyurea, with confirmed diagnosis of sickle cell disease (HbSS genotype) were treated with L-glutamine oral powder (~0.3 g/kg body weight) twice daily for 120 weeks. Of the enrolled patients, 4 patients were from Qatar with the Arab-Indian haplotype and 15 patients were from French Guiana with the African haplotype. The median age was 17 years (range 8 to 54 years) where 53% were <18 years of age. The median body weight of patients was 50 kilograms (range of 25 to 75 kilograms); 53% were males. Clinical events and laboratory parameters (hemoglobin, hematocrit, reticulocytes, and LDH) were collected or measured at baseline, 24, 48, 72, 96, and at 120 weeks. Baseline measures for VOCs, number of hospitalizations, hospitalization days, ACS events, and blood transfusions were collected for the 12 months prior to L-glutamine initiation. Changes from baseline to 120 weeks (annualized) were analysed using MedCalc statistical software Version 20.015. Results: Eighteen patients completed 120 weeks of the real-world L-glutamine treatment observation period. There were significantly fewer VOCs; median of 3 VOCs at baseline and median of 0 at 120 weeks. There were significantly fewer hospitalizations (median of 3 hospitalizations at baseline and 0 at 120 weeks), shorter hospitalization days (median of 15 days at baseline and 0 at end of the observation period), and fewer blood transfusions (median of 3 at baseline and 0 at 120 weeks). The change from baseline values to 120 weeks were significant (p < .00001) for VOCs, hospitalizations, days hospitalized, and the number of units transfused. The number of ACS events were also reduced from 11 at baseline to 0 at 120 weeks. Consistent with these findings, the mean increase in hemoglobin concentrations from baseline was 1.36 g/dL ± 0.17 SE and the mean percent increase in hematocrit from baseline was 5.85% ± 1.10 SE, both significantly improved at 120 weeks (p < .001) Figure 1A. Furthermore, mean reticulocyte counts decreased from baseline (-52.39 x 109/L ± 25.68 SE) and LDH levels decreased from baseline (-311.11 U/L ± 56.02 SE) both significantly changed at 120 weeks (p < .001) Figure 1B. Fewer number of patients were taking hydroxyurea at 120 weeks (8 patients) compared to baseline (12 patients). One patient died during the study (after the 72-week follow up visit) due to multiple deep vein thromboses resulting in a pulmonary embolism; this event was not related to L-glutamine treatment. Conclusion: In this long-term observational study, oral L-glutamine therapy in pediatric and adults living with sickle cell disease resulted in sustained clinical efficacy with improvements in hematologic parameters. L-glutamine therapy was well-tolerated by all patients and there were no safety concerns. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Characteristics and Clinical Outcomes in Patients (Pts) With Polycythemia Vera (PV) Receiving Ruxolitinib (RUX) After Hydroxyurea (HU): A Longitudinal Analysis From REVEAL

Background: Resistance or intolerance to first-line HU occurs in ~24% of pts with PV; RUX is a recommended second-line treatment (tx). In the large, real-world, multicenter, prospective Observational Study of pts with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159), demographics, disease burden, clinical management, and pt-reported outcomes data of pts with PV were collected from 227 community or academic centers between 2014 and 2019. This analysis describes the characteristics and clinical outcomes of pts with PV who switched to RUX after HU tx. Methods: This analysis included pts (≥18 y) with a clinical diagnosis of PV who were treated with HU at least 3 mo prior to study enrollment and did not switch to an alternative therapy during the observation period (index: study enrollment date) or who switched to RUX after previous HU tx (index: RUX initiation date). Descriptive statistics were used to describe demographics, disease characteristics, and tx patterns. Blood count, Myeloproliferative Neoplasm-Symptom Assessment Form total symptom score (MPN-SAF TSS), and spleen length measurements were analyzed at index and at 3 and 12 mo post index for pts who switched to RUX. Results:Characteristics of pts who switched to RUX vs who were treated with HU Out of 2510 pts enrolled in REVEAL,1053 were eligible for this analysis and comprised of 906 pts treated with HU and 147 who switched to RUX (Table 1). Median age for both groups at index was similar (RUX, 67 y; HU, 70 y); 44.2% and 51.8% were women in the RUX and HU groups, respectively. In RUX vs HU, median (range) time to index date from PV diagnosis was 6.9 (0.3-36.3) vs 4.8 (0.1-36.5) y. The median (range) duration of HU tx prior to index date was 27.6 (0.1-221.0) mo in the RUX and 26.7 (3.0-435.7) mo in the HU group. Main reasons for HU discontinuation prior to RUX tx were lack of efficacy (n=53, 36.1%), adverse events (n=47, 32.0%), and disease progression (n=10, 6.8%). Pts who switched to RUX vs HU had higher mean (SD) MPN-SAF TSS (27.5 [17.7] vs 17.3 [15.1]) and higher percentage of pts (n=40, 27.2% vs n=84, 9.3%) with a palpable spleen. At index, 26 (18.1%) vs 65 (7.8%) pts who switched to RUX vs HU had an elevated white blood cell (WBC) count, with mean (SD) of 16.1 (16.3) vs 9.2 (6.2) ×109/L, respectively. Mean (SD) number of phlebotomies (PHL) 6 mo prior to index date was 1.3 (2.3) in the RUX and 0.7 (1.45) in the HU groups. In RUX vs HU, 27.2% vs 19.3% had a thrombotic event (TE) history prior to index date. Tx patterns and clinical outcomes in pts who switched to RUX (n=147) Ninety-two pts (62.6%) received the recommended initial dose of RUX (10 mg BID); additional initial doses were 5 mg BID (n=19), 20 mg BID (n=16), 15 mg BID (n=10), and other (n=10). Seventy-two (49.0%) required a dose modification. The median (range) RUX tx duration was 22.6 (3.0-54.5) mo; most pts (89.1%) received RUX for ≥6 mo. At the end of study, 118 pts (80.3%) were still on RUX. Compared with index, MPN-SAF TSS, proportion of pts with palpable spleen, and spleen length decreased at 3- and 12-mo follow-up (Table 2). The number of pts with hematocrit >0.45 L/L decreased from 49 at index to 19 and 16 at 3 and 12 mo, respectively (Table 2). The number of pts with WBC counts >10×109/L decreased from 87 at index to 66 and 48 at 3 and 12 mo, respectively (Table 2). Pts with no blood count test at 3- or 12-mo follow-up more likely had controlled hematocrit/WBC at index. Mean (SD) number of PHL decreased from 1.3 (2.3) at index (6 mo prior) to 0.5 (1.3) after 6 mo; 110 pts (74.8%) no longer required PHL 12 mo after index date. The TE rate after index date was numerically lower in RUX vs HU (2.7% vs 4.2%) after a median follow-up of 26 and 44 mo, respectively. Conclusion: This analysis of REVEAL, the largest real-world cohort of PV pts to date, demonstrated that pts who switched from HU to RUX had more severe disease burden vs those who were treated with HU. RUX tx resulted in significant improvements in PV-related symptoms, correlating with reduction in spleen size and sustained improvement in hematologic parameters. This resulted in a reduction of PHL within 6 mo, with most pts becoming PHL-free at 12 mo. There was also a trend towards lower rates of TEs with RUX. This longitudinal analysis validates the efficacy of RUX for the tx of PV after HU exposure in the real-world and suggests monitoring of PV pts on HU to identify those who are likely to benefit from transition to RUX in order to meet tx goals and become PHL-free. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal