Total White Blood Cell Count Research Articles

Mechanisms and Therapeutic Strategies to Reverse TET2 Mutant Clonal Hematopoiesis and the Risk of MDS, AML, and Atherosclerotic Cardiovascular Disease

Inactivating mutations of the epigenetic modifier TET2 are frequent in myeloid malignancies and clonal hematopoiesis of indeterminate potential (CHIP). These mutations in hematopoietic stem and progenitor cells (HSPCs) impart a clonal advantage with increased self-renewal. CHIP is associated with an increased risk of hematological malignancies and, surprisingly, with atherosclerotic cardiovascular disease, supported by studies in mice and humans. The heightened cardiovascular risk in CHIP patients may result from a pro-inflammatory slant of the mutant HSPC progeny, particularly monocytes and macrophages, independent from the risk imparted by elevated LDL cholesterol levels. Targeting molecules like IL-1β may provide a strategy to lower the risk of cardiovascular morbidity in patients with CHIP. However, as an alternative strategy, administration of drugs that selectively suppress the growth of mutant CHIP clones in the bone marrow (BM) might reduce the risk of both i) progression to MDS or hematologic malignancy and of ii) atherosclerotic cardiovascular disease. This study focused on identifying drugs that reverse the inflammatory and atherosclerotic properties of TET2-mutant macrophages. Our previous investigations demonstrated that the nuclear export inhibitor eltanexor selectively kills Tet2-mutant HSPCs in zebrafish embryos and reduces the number of mutant colonies in murine colony formation assays. A murine competitive repopulation model of CHIP tested the in vivo efficacy of eltanexor. We found that eltanexor selectively reduces Tet2-mutant circulating monocytes while having no effect on overall total white blood cell counts. Moreover, a second trial using Ldlr-/- atherosclerosis-prone mice consuming a high-cholesterol diet, showed that treatment with eltanexor selectively reduces the amount of aortic atherosclerotic plaque formation as well as spleen weight in mice injected with Tet2+/- (mutant) BM cells, whereas eltanexor had no significant effect in mice injected with Tet2+/+ (wild-type) BM cells. Single-cell CITE-seq analysis of Ldlr-/- mice injected with a mix of Tet2+/- and Tet2+/+ BM cells showed that eltanexor selectively reduces the percentage of Tet2+/- HSPCs. Additionally, CITE-seq analysis revealed a significant reduction in pro-inflammatory macrophages in the arterial wall after eltanexor treatment, along with a decrease in IL-1β expression by these cells. As TET2 functions in mechanistically regulating gene regulation through epigenetic DNA methylation, we employed ChIP-seq and CUT&RUN-Seq technologies to investigate the mechanisms underlying enhancer dysregulation caused by loss of Tet2. Enhancer profiling of bone marrow-derived macrophages showed that the negative regulator of the macrophage inflammatory response, ATF3, is associated with a super-enhancer. Notably, the ATF3 super-enhancer emerged as the largest super-enhancer in wild-type macrophages but was reduced in Tet2-mutant macrophages. Our investigation also revealed that ATF3 binds with IL-1β at H3K27ac modified regions, and this binding was significantly diminished in Tet2-mutant macrophages. Remarkably, treatment with eltanexor restored the binding of ATF3 to IL1β, providing a mechanism to explain the anti-inflammatory effect of eltanexor concordant with our in vivo results. In summary, this study proposes eltanexor treatment as a novel therapeutic approach to specifically target TET2-mutant cells in individuals with CHIP and sheds light on the underlying mechanisms of the pro-inflammatory slant of TET2-mutant macrophages. These findings offer potential new avenues for precise therapies in humans with CHIP and associated cardiovascular risks from atherosclerosis.

Results of a Prospective Phase II Study of Individualized 6-Mercaptopurine Dosing Based on Pharmacogenomics in Childhood Acute Lymphoblastic Leukemia in East Asia

Introduction Variations in the NUDT15 and TPMT genes, which serve as pharmacogenomic markers for 6-mercaptopurine (6MP), contribute to individual differences in the optimal dosage of this medication. Nevertheless, given the observed difference in the tolerated dose of 6MP between East Asian and Western patients, it is essential to conduct a study to determine whether the same dosage guidelines are applicable to both populations. This study aimed to reduce treatment discontinuation and neutropenia during maintenance by adjusting the initial dose of 6MP based on the results of the NUDT15 or TPMT variants. M ethods This is a prospective phase II trial being conducted at three institutions in Korea. Patients who initiated 6MP-based maintenance treatment for acute lymphoblastic leukemia (ALL) were included in the study. During the maintenance phase, 6MP was administered at an individualized starting dose based on the NUDT15 and TPMT variants of each participant. Original dose (50 mg/m 2/day) of 6MP was administered to patients with both NUDT15 and TPMT wild-type, 30 mg/m 2/day for NUDT15 intermediate activity ( NUDT15 variant allele heterozygous) or TPMT heterozygosity, 10 mg/m 2/day for NUDT15 low activity ( NUDT15 variant allele homozygous), and 10 mg/m 2/day three times per week for homozygous TPMT variants. The maintenance cycle consists of 12 weeks of daily 6MP at an individualized dosage, weekly methotrexate (MTX) at a dosage of 20 mg/m 2, and monthly vincristine and steroid pulses. Lastly, intrathecally administered MTX is administered every three months. During treatment, the total white blood cell count was targeted to be between 2000/uL and 3000/uL, with an absolute neutrophil count greater than 500/uL and a platelet count greater than 50,000/uL. The whole exome was sequenced using genomic DNA extracted from peripheral blood at complete remission or hair follicles. As the primary and secondary endpoints, the duration of treatment discontinuation, the frequency of neutropenia, the presence of neutropenic fever during maintenance therapy, and the recurrence rate were compared to historical controls. A cohort of 254 patients who underwent maintenance therapy between the years 2001 and 2018 was chosen as the historical control group. Results Total 72 patients were enrolled from July 2019 until Aril 2022. This analysis was conducted on 52 patients who finished maintenance therapy. There were 32 males, and 20 females. The median age of the patients was 5.6 years (range, 2.2~15.9 years). The immunophenotypes of ALL was B-ALL in 40 patients, T-ALL in 10, Mixed phenotype in 1, and unspecified ALL in 1 patient. No patient had known pharmacogenetic variants in TPMT. The NUDT15phenotypes based on diplotypes included normal activity (n=41), intermediate activity (n=9), and low activity (n=2), occurring in 78.8%, 17.3%, and 3.8% respectively (Table 1). The number of days discontinued due to any toxicity during the 1 st cycle of maintenance therapy was average 7 days (max 59 days) in all patients, and that of the study group with intermediate enzyme activity phentypes was significantly shorter than in historical controls, with an average 6 days vs. 12 days ( P=0.03, Figure 1). The incidence of neutropenia during the 1 st cycle between two groups was not statistically different, however, among patients with NUDT15 or TPMT intermediate activity, the frequency of neutropenia was significantly lower in the study group ( P=0.03, Figure 2). The frequency of neutropenic fever (NF) and fever without neutropenia during the 1st cycle did not differ between the two groups. However, when patients with NUDT15 or TPMT intermediate activity were analyzed, no fever occurred in the study group of 9 patients, while NF and fever occurred in 11 and 8 patients in the control group (Figure 3). Conclusions Individualized administration of 6MP based on NUDT15 and TPMT genotypes during maintenance therapy in Korean pediatric ALL patients significantly reduced treatment discontinuation and febrile toxicity. A decrease in the initial dosage from 50 mg/m 2/day to 30 mg/m 2/day has the potential to reduce febrile toxicity in the patient group exhibiting intermediate activity of the NUDT15 enzyme, which is observed in approximately 20% of individuals in East Asia. Through this research, we expect to provide the dosing guidelines for 6MP in patients with ALL in East Asia.

Risk factors, antifungal susceptibility, complications, and outcome of Candida auris bloodstream infection in a tertiary care center in the western region of Saudi Arabia

BackgroundCandida auris, an emerging multidrug-resistant fungus species that grows as yeast, causes bloodstream infection, and is associated with high mortality rates. In this study, we identified risk factors associated with C. auris bloodstream infection, antifungal susceptibility pattern, complications, and outcome of the infection. MethodsThis single-center cross-sectional retrospective study was conducted at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia, which included all patients 18 years or above who have had one or more blood cultures for C. auris between January 2021 and December 2022. We aimed to identify the risk factors associated with C. auris bloodstream infection, antifungal susceptibility patterns, complications, and outcomes at our center. ResultsForty-six patients with C. auris-positive blood cultures were included. All the patients had healthcare-associated infections. The mean age was 64.67 years, and the majority of patients were male (73.9 %). The most common concomitant hospital-acquired infections were skin and soft tissue infections (37 %), followed by hospital-acquired pneumonia (34.8 %) and intra-abdominal infections (26.1 %). The mean total white blood cell count, procalcitonin, and C-reactive protein was 10.5 ± 5.99 × 109/L, 2.63 ± 4.82 μg/L, and 90.3 ± 64.1 mg/L, respectively. Hypertension (73.9 %) was the most common comorbidity, followed by diabetes mellitus (58.7 %) and renal dysfunction (54.3 %). Risk factors associated with C. auris candidemia included antibiotic use (91.3 %), especially for > 14 days (78.3 %), C. auris colonization (60.9 %), use of central venous catheters, especially when the catheter was in place for >30 days (80.4 %), ICU admission in the last 30 days before C. auris-positive blood culture (93.5 %), especially for more than two weeks (76.1 %), mechanical ventilation (89.1 %), total parenteral nutrition (13 %), previous intra-abdominal surgery (30.4 %), and immunosuppressive therapy (56.5 %). A total of 97.8 % of C. auris isolates were resistant to fluconazole and 17.4 % were resistant to amphotericin B. Endocarditis and endophthalmitis were reported in one (2.2 %) patient each. The all-cause mortality at 30 days was 47.8 %. ConclusionOur study is one of the few studies available globally on C. auris bloodstream infection that investigated risk factors, antifungal susceptibility, complications, and outcomes. A thorough screening and risk assessment strategy should aid infection control, preventing it from becoming a major concern in the future.

Utilizing liposomal encapsulation approach to address nephrotoxic challenges of colistimethate sodium through a preclinical study

The use of Colistin, a last-resort antimicrobial drug, carries the risk of acute kidney injury. The objective of the study was to assess the effectiveness of colistin-encapsulated liposomes (CL) in reducing nephrotoxicity. Additionally, a liposomal preparation of colistimethate sodium was formulated using the reverse phase evaporation method with a 3:1 ratio of phospholipids to cholesterol. The liposomal properties were evaluated using scanning electron microscopy, photon correlation spectroscopy, and release kinetic assay. The killing kinetics of the formulations on embryonic kidney cells were assessed using in vitro MTT reduction assay. The nephrotoxicity of CL and colistimethate sodium solution (CS) was evaluated in vivo by administering a dose of 20 mg/kg to rats every 12 h for 3 days, with a negative control group receiving a 0.9% saline solution (NSS). The study results revealed that monodisperses of CL showed a smooth surface and distinct boundaries, with an average size of 151.50 ± 0.46 nm and a narrow size distribution of 0.25 ± 0.01. The liposomal particles showed high entrapment efficiency of 96.45% ± 0.41%, with a ζ-potential of −60.80 ± 1.01 mV and a release rate of 50% of colistimethate sodium within the first 480 min. The CL induced nephrocytotoxicity in a concentration- and time-dependent manner. However, CS had notably lower IC50 values compared to its liposome preparations at 48 and 72 h (p < 0.05). In vivo study results show that serum levels of symmetric dimethylarginine (SDMA) and total white blood cell count (WBC) were significantly lower in the CL group (SDMA = 8.33 ± 1.70 μg/dL; WBC = 7.29 ± 0.99 log10 cells/mL) compared to the CS group (SDMA = 15.00 ± 1.63 μg/dL; WBC = 9.73 ± 0.51 log10 cells/mL). Our study findings enhance the understanding of the safety profile of CL and its potential to improve patient outcomes through the use of liposomal colistin medication. Additional clinical studies are necessary to establish the optimal safety regiment in humans.

Clinical characteristics of tracheobronchial Talaromyces marneffei infection in non-HIV-infected patients in South China

Objectives Tracheobronchial Talaromyces marneffei (T. marneffei) infections among non-HIV-infected patients are rare. To improve understanding, we analysed the clinical features, immune mechanisms, treatment, and prognosis. Methods Data on hospitalized patients with tracheobronchial T. marneffei infections from September 2013 to May 2022 were collected. The clinical and imaging features were analysed. Results Nineteen patients were enrolled, with a median age of 52 years (45–62 years). The most common symptoms were cough, expectoration, fever, weight loss, and anaemia. The total white blood cell and neutrophil counts, erythrocyte sedimentation rate, C-reactive protein, procalcitonin and globulin were increased, and the serum albumin levels were decreased. Chest CT manifestations included patchy shadows, masses, obstructive atelectasis, cavities, pleural effusion, and hilar and mediastinal lymphadenopathy. The fibreoptic bronchoscopy findings included masses, polyps or nodules with mucosal oedema, hypertrophic bulges, lumen stenosis or obstruction, and purulent secretions. T. marneffei infection was confirmed in 10 patients by positive culture, in five by both culture and metagenomic next-generation sequencing (mNGS), in two by mNGS, in one by culture and pathology and in 1 by histopathology. BALF (15/19, 78.9%) had the highest culture positive rate, followed by sputum (3/19), bronchial mucosa (1/1), lung biopsy (1/2); 36.8% of the patients were coinfected with other pathogens. For induction therapy, 7, 6, 2, and 4 patients received voriconazole, amphotericin B, voriconazole combined with amphotericin B, and fluconazole therapy, respectively, and 26.3% received treatment combined with nebulization and/or administration of amphotericin B under fibreoptic bronchoscopy. Four patients were treated for underlying diseases or coinfection, 31.6% were cured, 42.1% improved, and 26.3% died. Conclusions T. marneffei infection is common in the tracheobronchial airway tissue or secretions, and bronchoscopy has important diagnostic and treatment value. Antifungal therapy, including systemic therapy, involves triazoles and amphotericin administration, and aerosol inhalation and administration of amphotericin B under bronchoscopy are important.

Dynamic Modelling for Cancer-Associated Venous Thromboembolism

Background: Cancer-associated venous thromboembolism (VTE) is an important source of morbidity and mortality. Current risk prediction models for thrombosis are handicapped by static applicability (i.e. one-time evaluation prior to the first cycle of chemotherapy). We hypothesized that event forecasting using time series modelling could account for important changes in clinical state, variations in treatment and aspects of cancer progression over time. Methods: The cohort consisted of adult patients with a solid tumor enrolled in the MSK-IMPACT study between 2014 and 2019. VTE was defined as any symptomatic or asymptomatic pulmonary embolus or lower extremity deep vein thrombosis. We derived time series mixed-effects logistic regression models in order to predict cancer-associated VTE events using baseline patient characteristics (cancer type, time from diagnosis and age) along with time-dependent covariates including total white blood cell count, hemoglobin, platelet count, albumin, creatinine and parenteral chemotherapy type. Time-periods of one month were used and models were fitted to predict the presence or absence of a VTE episode in the following period (time = t+1) based on predictor values in the current period (time = t). The laboratory test result ascribed to a given period could be either the last value in the interval or the mean of all interval-specific values (both approaches tested). Missing laboratory results were imputed using the previously known value when available. Differences in laboratory values between periods t-1 and t were included as predictors in the initial model along with indicators of missingness (see Figure for flow of information between time-period cells). We hypothesized that absence of laboratory testing for a time-period would be a marker of stable medical state and hence associated with a lower risk of VTE. A previously defined training set comprising 80% of the cohort was used and different modelling approaches were evaluated using 5-fold cross-validation. The final selected model was evaluated in a separate dedicated validation set including the remaining 20% of the cohort. Results: The original cohort included 35,391 patients, from which 26,075 individuals with no cancer-associated VTE episode before observation start and sufficient laboratory test information could be included in the analysis, comprising 276,579 months of observation and 1,463 VTE events. The initial logistic regression model including all available predictors was fitted on the training set, revealing associations between predictors and VTE risk largely consistent with data reported by other groups (see Table). After adjusting for multiple comparisons, significant predictors of cancer-associated VTE identified included albumin, cell count result missingness (decreased risk for missing value), treatment with a platinum analogue (increased risk), hemoglobin, white blood cell count, breast cancer (decreased risk) and high-grade glioma (increased risk). Based on model metrics and prior knowledge from published literature, the set of covariates selected for inclusion in the final model consisted of cell counts along with the corresponding missingness indicator, platelet count change over time, albumin and chemotherapy types. The c-index for the final model using 5-fold cross-validation in the training set was 0.77 (95% CI = 0.75-0.80), compared to 0.77 (95% CI = 0.74-0.79) in the validation set. The latter corresponded to a specificity of 0.83 (95% CI = 0.79-0.86) when fixing sensitivity at 50%. Conclusions: A simple mixed-effects logistic regression time series model demonstrated promising potential to estimate the risk of cancer-associated VTE on a dynamic basis using routine laboratory test results and chemotherapy prescription data widely available in most electronic health record systems. Validation of this dynamic VTE risk model has the potential to optimize outpatient thromboprophylaxis during periods of high thrombotic risk.

Evaluation of the therapeutic efficacy of Vitex agnus-castus extract on cisplatin-induced hematotoxicity in female Wistar rats.

Cisplatin (CP) is a preferred drug for cancer treatment but it has dose-dependent side effects. Vitex agnus-castus (VAC) berry extract has antioxidant, free-radical scavenging, and anti-inflammatory activities. This study explored the mitigating effects of VAC extract (VACE) on acute hematotoxicity induced by CP in female Wistar rats. Female Wistar rats (n = 30) were randomly divided into five groups (n = 6/group). The normal control (NC) group received no treatment. The CP control group received CP (7 mg/kg.b.w. ip, single dose) and the drug control group (VACE-650) received VACE (650 mg/kg b.w. oral, daily) for 7 days. Both groups received a single dose of CP (7 mg/kg b.w. ip), followed by 350 and 650 mg/kg.b.w. of VACE daily orally (CPVACE-350 and CPVACE-650 groups, respectively) for 7 days. After a single dose of CP (7 mg/kg b.w.), the red blood cells (RBC), hematocrit (HCT), white blood cells (WBC), and platelets significantly decreased. In the VAC-350 group, the reduction in total WBC count was less than that in the VAC-650 group on the 3rd day. The RBC and HCT values of the VACE groups were better than that of the CP control, but the VACE-350 treatment group showed significant improvement only on the 3rd day. Our findings showed that VACE can mitigate CP-induced damage to peripheral blood cells at lower doses.

Neutrophilia is more predictive than increased white blood cell counts for short-term mortality after liver transplantation in patients with acute-on-chronic liver failure.

Acute-on-chronic liver failure (ACLF) is a life-threatening disease that requires urgent liver transplantation (LT). Accurate identification of high-risk patients is essential for predicting post-LT survival. The chronic liver failure consortium ACLF score is a widely accepted risk-stratification score that includes total white blood cell (WBC) counts as a component. This study aimed to evaluate the predictive value of total and differential WBC counts for short-term mortality following LT in patients with ACLF. A total of 685 patients with ACLF who underwent LT between January 2008 and February 2019 were analyzed. Total and differential WBC counts were examined as a function of the model for end-stage liver disease for sodium (MELD-Na) score. The association between total and differential WBC counts and 90-day post-LT mortality was assessed using multivariable Cox proportional hazards regression analysis. The total WBC counts and neutrophil ratio were higher in patients with ACLF than in those without ACLF. The neutrophil ratio was significantly associated with 90-day post-LT mortality after adjustment (hazard ratio [HR], 1.04; P = 0.001), whereas total WBC counts were not significantly associated with 90-day post-LT mortality in either univariate or multivariate Cox analyses. The neutrophil ratio demonstrated a relatively linear trend with an increasing MELD-Na score and HR for 90-day post-LT mortality, whereas the total WBC counts exhibited a plateaued pattern. Neutrophilia, rather than total WBC counts, is a better prognostic indicator for short-term post-LT mortality in patients with ACLF.

Evaluation of chronic alcoholics on haematological profiles in north central Nigeria

Misuse of alcohol is rapidly becoming a public health issue among society's adolescents and adults. The harmful use of alcohol ranks among the top five risk factors for disease, disability and death throughout the world. This study was conducted to determine selected haematological parameters among chronic alcoholics in Ilorin. A total of 70 participants with chronic alcoholism and 30 control samples were randomly selected to determine the possible haematological risks of the social behaviour with majority of participants being within the age range 18-65 years. The haematological parameters PCV, haemoglobin, red blood cell, platelet, and total white blood cell counts were determined using the Sysmex XN-300 instrument. The count of reticulocytes was done manually. The mean value of the subject RBC was decreased (3.45±1.25) in comparison with (4.75±0.66) of non-alcoholics. The results demonstrate a decrease in the subject's mean reticulocyte value (0.724±0.820) compared to (2.12±0.81) of the control, but the difference was not statistically significant. This study found that abstaining from alcohol consumption has no significant influence on red blood cell markers, however extensive drinking had negative implications on the immune cells. As a result, a clinical history of drinking during haematological examinations, may be beneficial and advised especially if the findings show a decrease in the number of immune cells.

High Fluorescent Cells on Automated Body Fluid Analysis as Discriminator for Malignant Cell Detection

The automated examination of body fluids (BF) serves as a valuable screening tool for the presence of malignant cells in such samples. Malignant cells are identified as high fluorescence cells (HFC) when analyzed using the Sysmex XN-1000 automated analyzer. This study aimed to assess the correlation between HFC cell counts generated by the automated analyzer and manual cytological examination for detecting malignant cells. Additionally, it sought to establish reliable cutoff values for malignant cells since there is a lack of literature on this subject. Conducted at the department of pathology hematology and cytology laboratory in a tertiary care hospital in India from January 2019 to May 2020, this hospital-based comparative study analyzed 120 BF samples, each subjected to cytological evaluation. The mean age of the study population was 52 years, with 70 male and 50 female patients (male-to-female ratio of 1.4:1). The samples consisted of 53 ascitic fluids (44.17%), 46 pleural fluids (38.33%), and 21 cerebrospinal fluids (CSF; 17.50%). Cytopathological examination revealed malignant cells in 50 (41.67%) of the BF samples, with 70 (58.33%) samples classified as nonmalignant. Specifically, among the ascitic fluids, 24 (48%) were malignant, while 29 (41.43%) were nonmalignant. For pleural fluids, 24 (48%) were malignant, and 22 (31.43%) were nonmalignant. In CSF, 2 (4%) samples were malignant, and 19 (27.14%) were nonmalignant. The total white blood cell counts provided by automated hematology analyzers were significantly higher in malignant samples, ranging from a minimum of 100 cells to a maximum of 60,000, with a median count of 800. Nonmalignant samples had white blood cell counts ranging from 2 to 12,000, with a median count of 100. Subgroup analysis for ascitic, pleural, and CSF samples revealed significantly higher median HFC counts in malignant samples. Receiver operating characteristic curve analysis indicated that the HF-BF parameter could effectively distinguish between benign and malignant fluids. For HF#, the area under the curve (AUC) was 0.844, with a sensitivity of 82% and specificity of 81%, while HF% had an AUC of 0.706, with sensitivity and specificity values of 72% and 72.9%, respectively. This study highlights that the HFC count in the BF mode of Sysmex XN-1000 can be a valuable tool for predicting the presence of malignant cells in serous fluids and for selecting samples for further microscopic examination. Based on this study, cutoff values of 15.70/µL for absolute HFC count and 5.05% for relative HFC count can be applied to screen BF samples for malignancy, offering good sensitivity and specificity.

The cost-effectiveness and value of C-reactive protein in the diagnosis and management of neonatal late-onset sepsis in resource-limited settings

Background. Although C-reactive protein (CRP) is used as a biomarker, its value in resource-limited settings for diagnosis andmanagement of late-onset sepsis in neonates has not been reported previously.Objective. To evaluate the value of CRP as a biomarker in identifying late-onset sepsis in symptomatic infants.Method. We performed a retrospective study to evaluate the value of CRP as a biomarker in identifying late-onset sepsis in symptomatic infants. Infants were classified into three groups (blood culture-proven sepsis (n=72), clinical sepsis (n=38) and no sepsis (n=114)). Infants underwent sepsis work-up consisting of complete blood count (CBC), blood culture, urine and cerebrospinal fluid (CSF) culture including CRP measurements.Results. The overall sensitivity and specificity of CRP levels >10 μg/mL was 94.5% and 91.2%, respectively, for the diagnosis of late-onset sepsis. Positive predictive value was 91.2% and negative predictive value was 92.8%. Total white blood cell (WBC) counts had poorsensitivity and specificity compared with CRP. The cost for CRP testing was only 2.5% of the total cost for sepsis work-up in neonates.Conclusion. Our study indicates that CRP has excellent sensitivity and specificity in the diagnosis of late-onset sepsis. In low- and middle-income countries, CRP testing perhaps offers more value compared with W14BC counts

Hematological Indices in Patients With Goiter: A Cross-Sectional Study in a Tertiary Care Hospital in South India.

Introduction A wide range of haematological abnormalities have been observed in patients with goitre. The aim of the study was to evaluate the abnormalities in haematological parameters among patients with goitre in a tertiary care hospital in south India. Methods This was a cross-sectional study carried out in the pathology department of Chengalpattu Medical College from April 1 to June 30, 2019. The lab reports, including the complete blood count (CBC) and serum thyroid profile that included thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) of all the patients with goitre, were retrieved from the laboratory records. Results were tabulated and analysed. Results Out of a total of 200 patients with thyroid dysfunction, 12 (6%) were males and 188 (94%) were females, with the majority (51.5%) of them in the age group of 30-60 years. Serum TSH levels showed a statistically significant association with red cell distribution width (RCDW) (P-value = 0.000), mean corpuscular volume (MCV) (P-value = 0.020), and total white blood cell (WBC) count (P-value = 0.003) among the patients with goiter. There was no significant association between TSH and other parameters like haemoglobin, packed cell volume (PCV), red blood cell (RBC) count, and platelet (PLT) count. Conclusions Red cell distribution width and mean corpuscular volume are useful haematological parameters that will help clinicians in the early diagnosis and proper treatment of haematological abnormalities seen in patients with goitre.

An Observational Study Comparing the Effects of Chloroquine and Artemisinin-Based Combination Therapy on Hematological Recovery in Patients With Plasmodium vivax Malaria.

Introduction Malaria, a common parasitic disease in tropical regions, produces hematological changes in patients. In the present study, we compare hematologic recovery between the chloroquine and artemether-lumefantrine treatment groups of patients with Plasmodium vivax malaria. Methodology This was a cross-sectional observational study comparing hematological parameters, including total and differential white blood cell counts, and platelet counts between two patient groups: one group with 48 patients receiving chloroquine, and the other with 47 patients receiving the artemether-lumefantrine combination. Both groups received primaquine to combat the hypnozoite stage. Results The rate of platelet count recovery was significantly faster in patients treated with the artemether-lumefantrine combination (p-value 0.002). Rates of recovery of the total white blood cell count and neutrophil count were faster with the artemether-lumefantrine combination, while the recovery of the lymphocyte count was faster in patients treated with chloroquine. However, these changes were statistically insignificant (p-values = 0.69, 0.42, and 0.65, respectively). Conclusion Based on hematological recovery, artemisinin combination therapy may be preferred over treatment with chloroquine in cases of P. vivax malaria. However, factors such as the adverse effect profile, cost-effectiveness, and chloroquine resistance need to be considered for the practical applicability of the same.

Macrocyclic lactone based tri-model therapy to treat humpsore in cattle under humid tropical island ecosystem

Humpsore is a chronic parasitic dermatitis in bovine species; induces severe economic losses to the dairy farmers. Various therapeutic methodologies were tried to treat humpsore in the past; however, they were partially effective against humpsore. Therefore, the present study was designed to assess the effect of tri-model therapy [macrocyclic lactone; Ivermectin, a piperazine derivative; diethylcarbamazine citrate (DECC) and an herbal ointment; Himax™] on treatment of humpsore in Andaman and Nicobar islands. Thirty‐six cattle (n=36 affected) were selected and divided into Gr 1: control (infected without treatment; n=18) and Gr 2: treatment group (infected with treatment; ivermectin, DECC and Himax, n=18) in South Andaman district. In Gr 2, treatment to the ailing animals was given for 45 days. Physiological profiles, hematological profiles, biochemical profiles [total protein, TP; albumin, AL; globulin, GL; creatinine, CR; glucose, GLU; total cholesterol, CHO and urea, URE], liver functional enzymes [aspartate aminotransferase, AST; alanine aminotransferase, ALT and alkaline phosphatase, ALP], mineral profiles, oxidative stress profiles [total antioxidant capacity, TAC; superoxide dismutase, SOD; catalase, CAT and malondialdehyde, MDA] and cortisol were estimated on day 30 of post treatment. Lesion was significantly reduced in day 15 of post‐treatment and completely healed on day 45 of post‐treatment in Gr 2. Physiological profiles, liver functional enzymes, urea, total white blood cell count, differential cell counts, MDA and cortisol were reduced significantly and blood profiles, biochemical profiles, mineral profiles and antioxidant profiles were increased significantly in tri-model therapy treated animals. Therefore, it can be concluded that tri‐model therapy is suitable to treat humpsore in dairy animals.

Very-low-calorie ketogenic diet vs hypocaloric balanced diet in the prevention of high-frequency episodic migraine: the EMIKETO randomized, controlled trial

BackgroundMigraine is the second world’s cause of disability. Among non-pharmacological treatments, nutritional intervention, particularly ketogenic diet, represents one of the most promising approaches.MethodsThis a prospective, single center, randomized, controlled study aimed at evaluating the efficacy of a very low-calorie ketogenic diet (VLCKD) compared to a hypocaloric balanced diet (HBD) in migraine prophylaxis in patients affected by high-frequency episodic migraine (HFEM) with a Body Mass Index (BMI) > 27 kg/m2. Fifty-seven patients were randomly assigned to a VLCKD (group 1) or HBD (group 2). Group 1 patients followed a VLCKD for 8 weeks, followed by a low calorie diet (LCD, weeks 9–12), and a HBD (weeks 13–24), whereas group 2 patients followed a HBD from week 0 to 24. Anthropometric indexes, urine and blood chemistry were assessed at enrollment, baseline, weeks 4, 8, 12, and 24. Migraine characteristics were evaluated at baseline, weeks 8, 12 and 24. Change in monthly migraine days (MMDs) at weeks 5–8 compared to baseline was the primary endpoint. Secondary endpoints encompassed changes in visual analogue scale (VAS), Headache Impact Test-6 (HIT-6) and Short Form Health Survey-36 (SF-36) scores. We also studied effects on circulating lymphocytes and markers of inflammation, changes in plasma aldosterone and renin levels before and after VLCKD or HBD treatment.ResultsReduction from baseline in MMDs was greater in VLCKD compared to HBD group at week 8 (p = 0.008), at week 12 (p = 0.007), when ketosis had been interrupted by carbohydrates reintroduction, and at week 24 (p = 0.042), when all patients were following the same dietary regimen. Quality of life scores (SF-36) were improved in VLCKD group at week 8 and 12, and were also improved in HBD group, but only at week 12. Weight-loss was significantly higher in VLCKD group at week 8 (p = 0.002) and week 12 (p = 0.020). At the end of the study weight loss was maintained in VLCKD group whereas a slight weight regain was observed in HBD group. Inflammatory indexes, namely C reactive protein (CRP), neutrophil to lymphocyte ratio (NLR) and total white blood cell count (WBC) were significantly reduced (p < 0.05) in VLCKD group at week 12. Aldosterone plasma level were significantly increased in both groups at week 8, particularly in VLCKD group. However, electrolytes and renin plasma levels were never altered throughout the study in both groups.ConclusionsVLCKD is more effective than HBD in reducing MMD in patients with HFEM and represents an effective prophylaxis in patients with overweight/obesity.Trial registration ClinicalTrials.gov identifier: NCT04360148.

COMPARISON OF HEMATOLOGIC DIFFERENCES WITH LITHIUM HEPARIN AND DIPOTASSIUM ETHYLENEDIAMINETETRAACETIC ACID IN EUROPEAN STARLINGS (STURNUS VULGARIS).

Preservation of blood through use of anticoagulants allows delayed assessment of hematologic health and is commonly employed in veterinary health assessments. The two most common anticoagulants are lithium heparin (LH) and dipotassium ethylenediaminetetraacetic acid (EDTA), and their effects can vary widely between species. The hematologic effects of these anticoagulants on blood from European starlings (Sturnus vulgaris) have not been established, and these birds could serve as models for passerine species both in managed collections and in the wild. Blood was drawn from 45 European starlings and immediately divided into either LH or EDTA microtainers. For each sample, packed cell volume (PCV), total solids (TS), and complete blood counts were performed. There were no significant differences between EDTA and LH anticoagulated blood for PCV, white blood cell count (WBC) slide estimates, WBC determined by Leukopet, absolute heterophils, absolute lymphocytes, absolute monocytes, absolute eosinophils, or absolute basophils. Blood anticoagulated with EDTA had higher total solids than blood mixed with LH. For both anticoagulants, Leukopet-measured total WBC were consistently higher than blood film estimates. There were no subjective morphologic differences for WBC and no hemolysis observed in the samples. Thrombocyte clumping was prominent for LH blood samples and minimal for EDTA samples. These results reveal that LH and EDTA are both suitable anticoagulants for use in European starlings, and EDTA may be superior for diagnostic purposes or for qualitative evaluation of thrombocyte quantity.

Shift Work is Associated with an Elevated White Blood Cell Count: A Systematic Review and Meta-Analysis.

The white blood cell (WBC) count increases significantly in reaction to infections and certain chronic diseases. Shift employment increases the risk for chronic low-grade inflammation and the progression of several chronic diseases. The objective of this study was to systematically evaluate the evidence from studies on total and differential WBC counts in shift employees. A literature search was performed in PubMed®, Web of Science, and Scopus databases using keywords for research published before March 1, 2022. A meta-analysis was conducted for total and differential WBC counts using a random-effects approach. A total of 25 studies covering a sample of 37,708 day and shift employees were included in this review. The studies represented America, Europe, East Asia, and Middle East. A significant increase in the total counts (×109/L) of WBC [mean difference (MD) = 0.43; 95% confidence interval (CI): 0.34-0.52; P < 0.001], lymphocytes (MD = 0.16; 95% CI: 0.02-0.30; P = 0.02), monocytes (MD = 0.04; 95% CI: 0-0.07; P = 0.03), and eosinophils (MD = 0.01; 95% CI: 0-0.01; P = 0.03) was observed in shift workers compared to the day counterparts. However, neutrophils and basophils were not significantly different between the groups. Shift work significantly increases the total and differential blood counts in peripheral circulation. Therefore, total and differential WBC counts represent a relatively inexpensive biomarker for diagnostics and prognostics of diseases in shift workers.

Unraveling Leukocyte Profile Shifts and Platelet Dynamics Following Leukoreduced Packed Red Cell Transfusions in Very Low Birth Weight Preterm Neonates.

Background Packed red blood cell (PRBC) transfusions are routine in neonatal care and the most common blood product administered to sick neonates. However, their impact on leukocyte and platelet profiles in very low birth weight (VLBW) preterm infants remains largely unexplored.This study examines leukocyte profile shifts and platelet dynamics following leukoreduced PRBC transfusions in VLBW preterm infants, offering insights to improve neonatal care and reduce unnecessary interventions. Methods The study utilized a retrospective cohort design within a single center, focusing on VLBW preterm infants who received PRBC transfusions at a level 3 NICU between January 2014 and June 2019. Data collection encompassed white blood cell (WBC) and platelet count measurements taken 24 hours before and up to 72 hours after PRBC transfusion. Neonates lacking complete blood count (CBC) data within the 72-hour post-transfusion window were excluded. A subgroup analysis distinguished the outcome between the initial PRBC transfusion and subsequent ones. The statistical significance of pre- and post-transfusion laboratory data was determined using the Wilcoxon signed ranks test and paired T-test. Results A cohort of 108 VLBW preterm infants who underwent a total of 402 PRBC transfusions was included in the analysis. The subjects exhibited a mean gestational age of 27.2 ± 2.5 weeks and a mean birth weight of 913 ± 264 grams. Analysis of pre- and post-transfusion data revealed no significant differences in total white blood cell count (WBC), absolute neutrophil count (ANC), absolute monocyte count (AMC), absolute eosinophil count, and absolute lymphocyte count. Notably, the platelet count was significantly decreased in the post-transfusion group (p < 0.001). In a subset analysis limited to the first-time transfusions among the 108 infants, a statistically significant increase was observed in total WBC, AMC, and ANC following transfusion. Conclusions The findings of this study highlight that PRBC transfusions can prompt an increase in neutrophils, monocytes, and eosinophils, coupled with a decline in platelet counts, all within a 72-hour window post-transfusion. Notably, these changes were predominantly discernible after the initial transfusion, with subsequent transfusions demonstrating consistency, except for the observed platelet count reduction. Recognizing these patterns could prove instrumental in averting undue investigations for suspected sepsis, particularly following the initial transfusion event. However, further in-depth investigations are necessary to uncover the underlying factors responsible for the shifts in leukocyte and platelet profiles triggered by PRBC transfusions.

Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Effect of periodic exposure to formaldehyde in the anatomy laboratory on some haematological indices in male Wistar rats

Background: The effect of periodic exposure to formaldehyde on some haematological indices in male Wistar rat was studied.&#x0D; Materials and Methods: The Wistar rats were divided into three groups A,B and C with 5 animals in each group. Group A served as control with nil exposure while groups B and C were the test groups with 5 months exposure on non-dissection days and dissection days respectively. Formaldehyde air level was measured both at experimental and control sites. Some haematological parameters measured include Red blood cell count, Haemoglobin concentration, White blood cell count: total and differential, and platelet count. Statistical analysis was done using Graph Pad Prism version 5.0. Results were presented as Mean ± SEM. Analysis of Variance was used to compare the means of test and control values while post hoc test was done using Student Newman Keul’s test and a P-value of less than 0.05 was considered as statistically significant.&#x0D; Results: Results revealed significant increase in formaldehyde air level in the dissection hall. There was significant increase in total white blood cell count when compared with control while red blood cell count, haemoglobin concentration and platelet count were not significant.&#x0D; Conclusion: It was therefore concluded that periodic exposure to formaldehyde in the Anatomy laboratory may have no effect on most haematological indices in Wistar rats although the white blood cells may be affected.