The purpose of the study was to investigate baseline inflammatory, hemostatic indicators and new-onset deep vein thrombosis (DVT) with the risk of mortality in COVID-19 inpatients. In this single-center study, a total of 401 COVID-19 patients hospitalized in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were enrolled from December 1, 2022 to January 31, 2023. The basic information, first laboratory examination results, imaging examination, and outcome-related indicators were compared between patients in the moderate and severe subgroups. We found that baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with new-onset DVT and death in severe hospitalized patients with COVID-19. The odds ratio (OR) of baseline D-dimer and baseline ANC with mortality was 1.18 (95% confidence interval [CI], 1.08-1.28; P < .001) and 1.13 (95% CI, 1.06-1.21; P < .001). Baseline ANC was associated with the risk of death in severe hospitalized COVID-19 patients, irrespective of the DVT status. In addition, a significantly higher serum neutrophil activity was observed in severe COVID-19 inpatients with DVT or those deceased during hospital stay. New-onset DVT partially mediated the association between baseline D-dimer (indirect effect: 0.011, estimated mediating proportion: 67.0%), baseline ANC (indirect effect: 0.006, estimated mediating proportion: 48.7%), and mortality in severe hospitalized patients with COVID-19. In summary, baseline D-dimer and baseline absolute neutrophil count (ANC) levels were associated with the mortality in severe hospitalized patients with COVID-19, especially DVT inpatients. New-onset DVT partially mediated the association between baseline D-dimer, baseline ANC, and mortality in severe hospitalized patients with COVID-19.

Normal absolute neutrophil count (ANC) variations, as seen with Duffy-null associated neutrophil count (DANC), are not accounted for in trial eligibility, which may contribute to racial enrollment disparities. We describe ANC eligibility for pediatric oncology phase I/II clinical trials according to primary sponsorship from 2010 to 2023 using ClinicalTrials.gov. Out of 438 trials, 20% were industry-sponsored. Total 17% of trials required ANC ≥1500 cells/μL for enrollment; however, industry-sponsored trials were significantly more likely to require ANC ≥1500 cells/μL than non-industry-sponsored trials (odds ratio 2.53, 95% confidence interval: 1.39-4.62; p < .001). These data suggest laboratory exclusion criteria are one possible mechanism for pediatric clinical trial enrollment disparities.

UNASSIGNED: Neutrophils are the most common cell types in circulation and are considered the first line of defense in the immune system against microorganisms. This study was undertaken to investigate the occurrence of isolated benign neutropenia (IBN) among healthy individuals in the central region of Saudi Arabia.
UNASSIGNED: This retrospective study analyzed complete blood count tests as part of routine checkups for chronic health conditions from April to September 2022. The 10,442 participants were randomly selected and their medical records were reviewed for neutropenia and mean absolute neutrophil counts (ANCs) were calculated. Descriptive analysis was employed to assess the prevalence of IBN across various demographic factors, such as age, gender, and nationality.
UNASSIGNED: The prevalence of IBN in the central region of Saudi Arabia was found to be 2.82% across the entire cohort of participants. The mean ANC among all participants was 4.55 × 109/L. The prevalence of neutropenia was higher in male participants compared with female. Male neutropenic had a lower mean ANC than female; however, the differences were not statistically different (P > 0.05). The prevalence of neutropenia was lower in Saudi participants compared with non-Saudis. While the mean ANC was lower among Saudis as compared with non-Saudi participants. However, the differences were not statistically different (P > 0.05).
UNASSIGNED: This is the first study from the central region of Saudi Arabia that determined the prevalence of chronic benign neutropenia among healthy individuals. The prevalence of IBN was found to be relatively low. Furthermore, neutropenia was more frequent in males than females. Moreover, male neutropenic individuals have a lower ANC.

BACKGROUND: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it is markedly underutilized, particularly in the US Black population, partly because of concern over clozapine-associated low absolute neutrophil count (ANC). People of African descent have a lower normative ANC range than the White population, which is associated with a specific \"ACKR1-null\" (\"Duffy null\") CC genotype (SNP rs2814778) on the ACKR1 gene, termed benign ethnic neutropenia (BEN). The range of ANC variability and safety of clozapine have not been established in people with BEN or examined prospectively in people of African descent.
METHODS: We completed a multisite, 6-month, prospective, open-label clinical trial of clozapine treatment in people of African descent with schizophrenia spectrum disorders for whom clozapine was clinically indicated, with or without the ACKR1-null genotype. We examined clozapine safety and weekly ANC during clozapine treatment and evaluated ANC variability by ACKR1-null genotype, sex, study site, and clozapine dosing using repeated measures analysis of covariance. Genotype was assayed using TaqMan® technology.
RESULTS: We enrolled 274 participants, of whom 227 (82.8 %) completed 6 months of clozapine treatment. There was one case of severe neutropenia (<500 cells/mm3) (0.36 %) over 1467.6 person-months of clozapine exposure. This participant recovered without sequelae after discontinuation of clozapine. Of the 249 participants with known genotypes, 199 (79.9 %) had the ACKR1-null genotype. Neutropenia (<1500 cells/mm3) occurred significantly more often in the ACKR1-null group (33 % [65/199]) than in those with the T allele (6 % (3/50); p < 0.001). Fourteen (5 %) patients discontinued due to adverse events. Rates of infection and fever were low and sialorrhea was the commonest side effect (N = 187, 68 %).
CONCLUSIONS: To our knowledge, this is the largest prospective clozapine trial in people of African descent. Severe neutropenia was rare, despite the high prevalence (80 %) of the ACKR1-null genotype. Our findings suggest that clozapine can be used safely in Black patients including those with BEN.

Higher number of monocytes and neutrophils may correlate with active tuberculosis (TB) in children. However, the few paediatric studies available are limited by the small numbers of children with TB disease or infection included.
We calculated the monocyte-to-lymphocyte-ratio (MLR), neutrophil-to-lymphocyte-ratio (NLR) and neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) in children with active TB, latent TB infection (LTBI), other infectious and non-infectious conditions and healthy children evaluated in two referral centres in Rome.
Overall, 649 children were included (41.8% females, mean age of 5.74 years). MLR, NLR and NMLR values were always significantly higher in patients with TB compared with the other groups (p < 0.001). Considering the entire population with the outcome of TB diagnosis, NMLR, with a cut-off of 1.2, had a sensitivity of 63% and a specificity of 76% (AUC: 0.71 [0.64-0.78]); NLR, with a cut-off of 1.5, had a sensitivity of 61% and a specificity of 79% (AUC: 0.72 [0.65-0.79]); MLR, considering a cut-off of 0.2, was less sensitive (56%) but more specific (82%) with a similar AUC (0.72 [0.65-0.79]).
Our study provides further evidence that MLR, NLR and NMLR can serve as first level diagnostics to support the clinical suspicion of TB in children.

BACKGROUND: Patients with multiple comorbidities who have coronavirus disease 2019 (COVID-19) have high morbidity and mortality. Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to have an enhanced effect on coronavirus in an earlier study.
METHODS: We conducted this comparative observational study to evaluate the effects of COVID-19 disease on G6PD deficiency based on the hematologic parameters, COVID-19-related hospitalizations, and mortality in the state of Qatar between January 2020 and May 2020 at four designated COVID-19 facilities. We identified 41 patients with G6PD deficiency who had documented COVID-19 infection. We compared the results with 241 patients with COVID-19 infection who tested negative for G6PD deficiency.: Results: Comparing the COVID-19 positive G6PD deficient with COVID-19 positive G6PD normal activity showed that G6PD normal group had higher white blood cell count (WBC), absolute neutrophil count (ANC), lymphocytes, eosinophils, and monocytes counts versus the G6PD deficient group (p < 0.001).
CONCLUSIONS: When compared with COVID-19 patients with normal G6PD, patients with COVID-19 infection and G6PD deficiency had lower total WBC, ANC, lymphocyte, monocyte, and eosinophil counts. However, no evidence of increased hemolysis, thrombosis, morbidity, or mortality was observed in COVID-19 patients with G6PD deficiency.

Introduction The COVID-19 pandemic gained ground in India, starting from a few cases and spreading to the whole country; eventually becoming the second-most affected country worldwide. Here, we present the clinical and laboratory profile and the risk factors associated with mortality in COVID-19. The study comes from Kerala, a region that reported the first case in India. Kerala has the second-highest case burden in the country but also has managed to keep the case fatality rate down below the national average. Methodology This is a single-center retrospective cross-sectional study on 391 laboratory-confirmed COVID-19 positive inpatients between September 2020 and October 2020. Hematological parameters, coagulation parameters, liver function tests (LFT), and renal function tests (RFT) results were collected and compared among survivors and non-survivors to identify predictive biomarkers of mortality. Results The mean age of all patients was 53.2 years (SD 17.0). On bivariate analyses, the mean values of total leukocyte count (TLC), absolute neutrophil count (ANC), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP), ferritin, lactate dehydrogenase (LDH), D-dimer at admission, prothrombin time international normalized ratio (PT INR), blood urea nitrogen (BUN), and creatinine were significantly higher in non-survivors than in survivors: mean (SD) 11.9 (7.6) vs 7.5 (4.2) (x109/L), 10.5 (7.4) vs 5.3 (4.1) (x109/L), 11.6 (13.5) vs 3.4 (3.5), 185 (117) vs 48 (85) (mg/L), 829.4 (551.2) vs 323.6 (374.1) (ng/ml), 905.5 (589.1) vs 485.1 (353.9) (U/L), 4.01 (3.53) vs 1.29 (2.08) (µg/ml), 1.21 (0.42) vs 0.99 (0.18), 105.1 (91.4) vs 33.6 (31.0) (mg/dl), 3.6 (4.1) vs 1.1 (1.6) (mg/dl), respectively, p < 0.001. Absolute lymphocyte count, serum albumin, and albumin/globulin (A/G) ratio were lower in non-survivors than in survivors (mean (SD) 1.3 (1.0) vs 2.0 (0.9) (x109/L), p < 0.001; 3.0 (0.7) vs 3.8 (2.1) (g/dl), p 0.005; 0.9 (0.3) vs 1.2 (0.4), p < 0.001). Multivariate analysis identified ANC, D-dimer at admission, CRP, and BUN as independent prognostic factors associated with mortality. Conclusion Several accessible tests like TLC, ANC, NLR, and BUN can be used in low-resource settings to assess severity in patients with COVID-19. In addition, ANC, D-dimer at admission, CRP, and BUN can be used as independent predictors of in-patient mortality in COVID-19 patients in hospital settings.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, pegfilgrastim) is a long-acting derivative of recombinant human granulocyte colony-stimulating factor with limited renal clearance and a longer half-life. It is used for the prevention of febrile neutropenia, owing to its capacity to promote neutrophil recovery. In this study, the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of 2 formulations of PEG-rhG-CSF were evaluated in healthy Chinese subjects. Twenty-four male subjects who received a single dose of subcutaneous PEG-rhG-CSF 100 µg/kg were randomized to either treatment A (3 mg/mL) or treatment B (1 mg/mL). Noncompartmental pharmacokinetic parameters of PEG-rhG-CSF were derived from serum concentration-time data. In addition, absolute neutrophil count (ANC) as a pharmacodynamic maker, immunogenicity through antidrug antibody testing, and safety were evaluated. The mean area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-t ) and the mean maximum concentration (Cmax ) of PEG-rhG-CSF after treatment A were 5070 ng·h/mL and 125 ng/mL, respectively; these values were comparable to those measured after treatment B (5340 ng·h/mL and 123 ng/mL, respectively). The mean value of area under the △ANC (baseline-adjusted ANC)-time curve and the maximum △ANC values were 4380 × 109  h/L and 33.1 × 109 /L, respectively, in the treatment A group, and 5170 × 109  h/L and 38.6 × 109 /L, respectively, in the treatment B group. The pharmacokinetic and pharmacodynamic profiles were similar for the 2 PEG-rhG-CSF formulations following a single dose of 100 µg/kg. The safety and immunogenicity profiles were also similar, with no significant differences. The dose adjustment of PEG-rhG-CSF was not considered necessary for formulation transformation.

BACKGROUND: Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment. Infections such as febrile neutropenia (FN) are sensitive to the duration of neutropenia as well as the depth of absolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte colony stimulating factor (G-CSF), can stimulate the function of mature neutrophils. Pegfilgrastim, a long-acting form of filgrastim, has been shown to reduce FN to a greater extent compared to filgrastim. G-CSF agents have been recommended for prophylactic administration with chemotherapy. Apotex developed a proposed pegfilgrastim biosimilar. This study was conducted to confirm that no clinically meaningful efficacy or safety differences exist between Apotex\'s proposed biosimilar and its reference product.
METHODS: 589 breast cancer patients were randomized and dosed with the proposed pegfilgrastim biosimilar, US-licensed pegfilgrastim reference product, or EU-approved pegfilgrastim reference product. The primary endpoint assessed was the duration of severe neutropenia (DSN) and secondary endpoints included rate of FN and ANC nadir.
RESULTS: Data showed that the mean DSN, the primary endpoint measured, was comparable across all three treatments. The As Treated arm had a 95% confidence interval within the equivalence range for the proposed pegfilgrastim biosimilar with the US-licensed and EU-approved pegfilgrastim reference products. Secondary endpoints, which included depth and peak of ANC nadir, time to ANC recovery post-nadir and rates of FN, also showed similarity between the three different treatment groups. The adverse event incidence was similar across treatment arms and there were no unexpected safety events.
CONCLUSIONS: Overall, these results show that the proposed pegfilgrastim biosimilar is similar to Amgen\'s US-licensed and EU-approved pegfilgrastim reference products with regard to the clinical efficacy and safety endpoints assessed.Trial registration EMA: European Union Clinical Trials Register: (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002678-21) Eudract # 2011-002678-21 Registered: 01/10/2012.

BACKGROUND: The prognostic relevance of a high blood neutrophil-to-lymphocyte ratio (NLR) has been reported in many cancers, although, to our knowledge, not investigated in patients with Merkel cell carcinoma (MCC) to date.
OBJECTIVE: We assessed whether the NLR at baseline was associated with specific survival and recurrence-free survival in MCC.
METHODS: We retrospectively included MCC cases between 1999 and 2015 and collected clinical data, blood cell count at baseline, and outcome. A Cox model was used to identify factors associated with recurrence and death from MCC.
RESULTS: Among the 75 patients included in the study, a high NLR at baseline (NLR ≥4) was associated with death from MCC in univariate (hazard ratio 2.76, 95% confidence interval 1.15-6.62, P = .023) and multivariate (hazard ratio 3.30, 95% confidence interval 1.21-9.01, P = .020) analysis, but not with recurrence.
CONCLUSIONS: Because of the retrospective design, we excluded patients with missing data and not all confounding factors that may influence the NLR were available.
CONCLUSIONS: A high NLR at baseline was independently associated with specific mortality in patients with MCC. The NLR seems to constitute an easily available and inexpensive prognostic biomarker at baseline.