Total White Blood Cell Count Research Articles

Unilateral Periorbital Necrotizing Fasciitis – A Case Report

IntroductionPeriorbital necrotizing fasciitis is rare due to the excellent blood supply to the area, but nevertheless can sometimes lead to death. Knowledge of the symptoms of the disease enables rapid diagnosis, which reduces the possibility of serious complications of the disease and its mortality. To date, few publications describing the disease entity have been presented.Patient descriptionA 70-year-old male patient was admitted to the hospital with necrotizing fasciitis of the left upper eyelid region, diagnosed on the basis of fulminant development of necrosis and a positive bacteriological test for S. pyogenes.ResultsContrast-enhanced computed tomography showed the presence of a pathological inflammatory infiltrate within the eyelid of the left eye and subcutaneous tissue at the preseptal level of the orbit and left cheek. Blood tests showed leukocytosis (total white blood cell count of 17.33 x 109/ L with 87.1% neutrophils) and elevated C reactive protein parameters (240.64 mg/ L). Empirical intravenous antibiotic therapy was administered: 1 g of amoxicillin with 200 mg of clavulanic acid every 8 hours, 500 mg of metronidazole every 8 hours, and ciprofloxacin into the left and right conjunctival sacs 3 mg/ml every 6 hours. Surgical debridement of upper eyelid necrosis was performed on the second day of hospitalization.ConclusionsThe peculiar anatomical structure of the periocular region promotes the dynamic development of necrotizing fasciitis. The close proximity of the central nervous system and the eyeball threatens irreversible consequences, including loss of vision or death. Early appropriate targeted treatment can effectively stop the development of the disease and prevent severe complications.

Association Between Highly-Sensitive C- Reactive Protein and Neutrophil to Lymphocyte Ratio as Markers of Inflammation Among Adult Nigerians with Essential Hypertension

Background: Hypertension is a medical condition with global public health importance that is associated with significant morbidity and mortality in both developed and developing countries. It is important to identify readily available parameters that may indicate the level of inflammation that is associated with hypertension. Objective: To assess the relationship between highly-sensitive C-Reactive Protein (hs-CRP) and neutrophil-to-lymphocyte ratio (NLR) in hypertensive adults. Methods: Three hundred and sixty adults comprising 240 hypertensive and 120 healthy normotensive subjects (control) were studied. The full blood count (FBC) and highly-sensitive C-Reactive Protein (hs-CRP) levels were determined using standard methods. Results: The mean values of Total White Blood Cells count (WBC) (p = 0.03), absolute neutrophil count (p = 0.03), absolute lymphocyte count (p = 0.01), NLR (p = 0.001) and hs-CRP (p <0.001) in the hypertensive subjects were significantly higher than in the normotensive subjects. The mean values also differed significantly with increasing severity of hypertension. There was a significant but weak positive correlation between NLR and hs-CRP (r = 0.248, p <0.001). The Areas Under the Curve (AUC) of the Receiver Operating Characteristic (ROC) of NLR and hs-CRP (p = 0.01) were 0.68 and 0.639 respectively. Conclusion: NLR is closely associated with hs- CRP among hypertensive subjects. Therefore, NLR may be utilised routinely instead of hs-CRP as a screening test for inflammation in essential hypertension.

Immune and oxidative stress biomarkers in pediatric psychosis and psychosis-risk: Meta-analyses and systematic review

ObjectiveWhile genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and adolescents. MethodsWe conducted a systematic review to identify immune and redox biomarker studies in children and adolescents (mean age ≤ 18 years old) across the psychosis spectrum: from psychotic like experiences, which are common in children, to threshold psychotic disorders like schizophrenia. We conducted meta-analyses when at least three studies measured the same biomarker. ResultsThe systematic review includes 38 pediatric psychosis studies. The meta-analyses found that youth with threshold psychotic disorders had higher neutrophil/lymphocyte ratio (Hedge’s g = 0.40, 95 % CI 0.17 – 0.64), tumor necrosis factor (Hedge’s g = 0.38, 95 % CI 0.06 – 0.69), C-reactive protein (Hedge’s g = 0.38, 95 % CI 0.05 – 0.70), interleukin-6 (Hedge’s g = 0.35; 95 % CI 0.11 – 0.64), and total white blood cell count (Hedge’s g = 0.29, 95 % CI 0.12 – 0.46) compared to youth without psychosis. Other immune and oxidative stress meta-analytic findings were very heterogeneous. ConclusionResults from several studies are consistent with the hypothesis that signals often classified as “proinflammatory” are elevated in threshold pediatric psychotic disorders. Data are less clear for immune markers in subthreshold psychosis and redox markers across the subthreshold and threshold psychosis spectrum. Immune and redox biomarker intervention studies are lacking, and research investigating interventions targeting the immune system in threshold pediatric psychosis is especially warranted.

The Effects of Hyperglycaemia on the Chemotherapy of Diminazene aceturate in Trypanosoma brucei-infected Dogs

The effects of hyperglycaemia on the outcome of treatment with diminazene aceturate in dogs infected with Trypanosoma brucei was evaluated using the following parameters; parasitaemia, packed cell volume, red blood cell count, haemoglobin concentration, total white blood cell count and differential counts, survivability, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total protein, and cholesterol. A total of 12 Nigerian local dogs, of both sexes were used in this study. They were randomly, assigned into four groups of three dogs each. Group A was uninfected non hyperglycaemic non treated, group B infected non hyperglycaemic treated, group C infected hyperglycaemic non treated and group D infected hyperglycaemic treated. No mortality was recorded in group A, while groups B, C and D survived 33%, 100% and 67% mortalities respectively. There was total clearance of the parasites in the treated groups (B and D) on days 18 and 20 post infection (PI) respectively (days 6 and 8 post treatment). However, there was a relapse of infection in group D on day 22 PI (day 11 PT) and no relapse occurred in group B. Infections caused a significant decrease (p<0.05) in all the red cell parameters (PCV, Hb concentrations and RBC counts) in group C, but no significant (P>0.05) decrease was observed in groups C and D. The mean AST and ALT of group D were significantly (P<0.05) higher than the other groups, while the mean ALP of groups A and D did not show any significant (P>0.05) difference, but were significantly (P<0.05) lower than groups C and B. The mean total protein of group A was significantly (P<0.05) higher than the infected groups, while the infected groups C, B and D did not show any significant (P>0.05) difference. It was concluded from the study that, hyperglycaemic resulted in diminished effectiveness of diminazene aceturate in Nigerian local breeds of dogs

Mean platelet volume and total white blood cells as diagnostic biomarkers for acute appendicitis at Omdurman military hospital: a cross-sectional study − 2021

BackgroundAcute appendicitis (AA) is among the most common nontraumatic indications for emergent abdominal surgical procedures. However, accurately diagnosing all cases can be challenging, physical examination, biochemical markers, and imaging techniques can sometimes be insufficient. This study aimed to (a) compare the mean platelet volume (MPV) and total white blood cell count (TWBCs) in patients with or without histological evidence of an inflamed appendix and (b) determine the positive predictive value, negative predictive value, sensitivity, and specificity of both MPV and TWBCs as diagnostic biomarkers in the diagnosis of AA. We conducted this research at Omdurman Military Hospital, focusing on patients who presented with symptoms suggestive of AA.Materials and methodsAn analytical cross-sectional study conducted at Omdurman Military Hospital from December 2020 - December 2021. The study population was patients who presented to our emergency department with symptoms and signs suggestive of AA. Participants were patients operated on as cases of AA. Data variables included sociodemographic characteristics, clinical presentations, intraoperative appendix macroscopic findings, preoperative MPV and total white blood cell count (TWBCs), and postoperative histopathological findings.ResultsA total of 106 patients were included in this study, with 75 (68.2%) males; half were 10–19 years old. Sixty-three patients (57.3%) had low (< 7.5 fL) MPV, whereas 47 (42.7%) had normal values. Comparing MPV to total white blood cells (TWBCs) revealed that MPV was more sensitive (84.6%) and specific (90%) than TWBCs during the first 24 h of inflammation. However, the TWBCs were more sensitive (97.2%) but less specific (94.7% vs. 100%) after 24 h of onset.ConclusionIn this study, MPV was lower in patients with AA, while there was an increase in TWBCs. The high sensitivity and specificity of TWBCs and MPV indicated that they form a promising diagnostic marker for AA.

Does the provision of live black soldier fly and yellow mealworm larvae improve Muscovy duck welfare?

BackgroundThe provision of environmental enrichments to Muscovy ducks could reduce the expression of the aggressive behaviors. The aim of the present study was to evaluate the effects of black soldier fly (BSF) and yellow mealworm (YM) live larva provision on Muscovy duck performance, excreta corticosterone metabolites (ECM), behavior, and blood parameters.MethodsA total of 126 3-day-old female Muscovy ducklings were allotted to 18 pens (6 replicates/treatment, 7 birds/pen) and assigned to 3 experimental treatments: a control group fed commercial feed, and two experimental treatments fed commercial feed plus the 5% (based on the expected daily feed intake, as fed basis) of BSF and YM live larvae (BSF and YM groups, respectively). A two-phase feeding program was applied: starter (from 3 to 31 days of age) and grower-finisher (from 32 to 55 days of age). The live weight, average daily gain, average daily feed intake, and feed conversion ratio were calculated. Larva consumption times were collected, and video recordings were performed during 3 periods (P) each day: the hour before (P1), during (P2), and after (P3) the larva administration. ECM were evaluated at 3, 31, and 55-day-old. Finally, the total red and white blood cell counts, serum proteins, lipids, and liver and renal function serum enzymes were evaluated on 12 birds/treatment.ResultsThe experimental treatment did not affect the growth performance of the birds (P > 0.05). Larva consumption times were always similar between the two insect species, except at 14–18 days of age, were BSF larvae were consumed faster than YM larvae (P < 0.001). The birds showed less walking activity during P2, and preening behavior increased in YM birds during P3. The C birds increased the attack behavior over the weeks (P < 0.05). During weeks 1–3 the YM group reduced the attack frequency (P1 > P3; P < 0.05). Finally, the provision of live BSF and YM larvae significantly reduced the ECM at 55 days of age and the heterophil to lymphocyte ratio (P < 0.05).ConclusionsLive BSF and YM larva supplementation in Muscovy duck improves duck welfare, without impairing birds’ growth performance.

Exploring the multifaceted effects of Ammi visnaga: subchronic toxicity, antioxidant capacity, immunomodulatory, and anti-inflammatory activities

ABSTRACT Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.

Evaluate the hematologic parameters, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with autoimmune hypothyroidism from Amara City, Southern Iraq

Abstract Background: Thyroid diseases are affecting 3%–5% of the women general population. Autoimmune thyroid diseases such as Graves’ disease (GD) and Hashimoto’s disease were detected to be the commonest disorders affecting thyroid function. Objectives: This study is a case–control study that aimed to estimate the effect of HT on hematological parameters. Materials and Methods: A total of 100 persons (50 HT patients and 50 euthyroid groups) of both sexes aged between 15 and 50 years were included in this study during the period April 2021–April 2022. Samples of venous blood (5 mL) were obtained from the study participants and used for the estimation of serum thyroid-stimulating hormone (TSH), FT3, and FT4 levels, as well as anti-thyroid peroxidase (TPO), anti-thyroglobulin (TG) concentration, as well as hematologic parameters. Results: The results of this study showed that HT patients had significantly higher levels of TSH as well as thyroid autoantibodies (anti-TPO and anti-TG) and significantly lower levels of FT3 and FT4. A considerable decrease was found in the hematocrit, hemoglobin, and mean corpuscular volume among HT patients, whereas no significant differences were found between the HT patients and the euthyroid group in total red blood cell count, total white blood cell count, neutrophils, lymphocytes, monocytes, basophils, platelet counts, MPV, mean distribution width, plateletcrit, and PLCR. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) values were significantly higher in the HT patients compared with the euthyroid group. Conclusions: The current study concluded that Hashimoto’s thyroiditis is associated with significant elevation in the serum concentrations of anti-TPO and anti-TG antibodies, high TSH levels, and decreased FT3 and FT4 levels. Hashimoto’s disease resulted in a significant decrease in the hemoglobin concentration; hence, patients with HT could be at risk to have anemia. Also, HT was associated with elevated NLR and PLR values; therefore, NLR and PLR ratios could be used as routine, inexpensive, easily accessible markers at the clinical course or the severity of autoimmune diseases that progress with chronic inflammation.

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&amp;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 &amp;lt; 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 &gt;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.