Sysmex DI-60 enumerates and classifies leukocytes. Limited research has evaluated the performance of Sysmex DI-60 in abnormal samples, and most focused on leukopenic samples. We evaluate the efficacy of DI-60 in determining white blood cell (WBC) differentials in normal and abnormal samples in different WBC count. Peripheral blood smears (n = 166) were categorised into normal control and disease groups, and further divided into moderate and severe leucocytosis, mild leucocytosis, normal, mild leukopenia, and moderate and severe leukopenia groups based on WBC count. DI-60 preclassification and verification and manual counting results were assessed using Bland-Altman and Passing-Bablok regression analyses. The Kappa test compared the concordance in the abnormal cell detection between DI-60 and manual counting. DI-60 exhibited notable overall sensitivity and specificity for all cells, except basophils. The correlation between the DI-60 preclassification and manual counting was high for segmented neutrophils, band neutrophils, lymphocytes, and blasts, and improved for all cell classes after verification. The mean difference between DI-60 and manual counting for all cell classes was significantly high in moderate and severe leucocytosis (WBC > 30.0 × 109/L) and moderate and severe leukopenia (WBC < 1.5 × 109/L) groups. For blast cells, immature granulocytes, and atypical lymphocytes, the DI-60 verification results were similar to the manual counting results. Plasma cells showed poor agreement. In conclusion, DI-60 demonstrates consistent and reliable analysis of WBC differentials within the range of 1.5-30.0 × 109. Manual counting was indispensable in examining moderate and severe leucocytosis samples, moderate and severe leukopenia samples, and in enumerating of monocytes and plasma cells.

UNASSIGNED: Lorlatinib is a new generation ALK kinase inhibitor. We describe a 52-year-old patient with ALK-positive advanced lung adenocarcinoma who achieved remission after multi-line therapy combined with paraneoplastic leukemoid reaction treated with Lorlatinib.
UNASSIGNED: A 52-year-old male patient was diagnosed with stage IV right lung adenocarcinoma, ALK: (+), previously received oral Crizotinib and Alectinib. Blood routine showed white blood cells abnormally elevated after disease progression, and maximum white blood cell count was 179.14×10^9/L. The patient was enrolled in study entitled \"a phase II, multicenter, open-label, dual-cohort study to evaluate the efficacy and safety of LORLATINIB monotherapy in ALK inhibitor-treated locally advanced or metastatic ALK-positive non-small cell lung cancer patients in China\". With oral Lorlatinib, the white blood cell count decreased from 179.14×10^9/L to normal after two weeks of administration. PFS was 4.5 months. When follow up imaging showed lesions progression, the white blood cell count increased again, diagnosing a paraneoplastic leukemic reaction. OS was 5.2 months.
UNASSIGNED: In this case, fourth-line Lorlatinib treatment is effiective in ALK-positive advanced patient with paraneoplastic leukemoid reaction. ClinicalTrials.gov Identifier: NCT03909971.

BACKGROUND: Comprehensive research on the effects of individual benzene, toluene, ethylbenzene, and xylenes (BTEX) and their mixture measured in blood samples, on cardiovascular diseases (CVD) and related risk factors among the general population is limited.
OBJECTIVE: To investigate the effects of blood individual and mixed BTEX on total CVD and its subtypes, lipid profiles, and white blood cell (WBC) count.
METHODS: Survey-weighted multivariate logistic regression was used to examine the associations between blood individual and mixed BTEX with CVD and its subtypes in 17,007 participants from NHANES 1999-2018. The combined effect of BTEX mixture on CVD was estimated using weighted quantile sum modeling and quantile g-computation. Weighted multivariate linear regression assessed the effects of BTEX on lipid profiles and WBC, including its five-part differential count.
RESULTS: In comparison to the reference quartile of BTEX mixture, individuals in the highest quartile had a significantly increased adjusted odds ratio of CVD risk (1.64, 95 % CI: 1.23 to 2.19, P for trend = 0.008). Positive associations were observed for benzene, toluene, ethylbenzene, and m-/p-xylene, demonstrating a monotonically increasing exposure-response relationship. Mixed BTEX was associated with congestive heart failure (CHF), angina pectoris, and heart attack. Individual benzene, toluene, and ethylbenzene were associated with CHF, while toluene, ethylbenzene, and all xylene isomers were linked to angina pectoris. Benzene, toluene, and o-xylene were associated with heart attack. Both mixed and individual BTEX showed positive associations with triglycerides, cholesterol, low-density lipoprotein, and WBC, including its five-part differential count, but a negative relationship with high-density lipoprotein. Subgroup analyses identified modifying effects of smoking, drinking, exercise, BMI, hypertension, and diabetes on the associations between specific toxicants and CVD risk.
CONCLUSIONS: Exposure to BTEX was associated with cardiovascular diseases and cardiovascular risk factors. These findings emphasize the importance of considering blood BTEX levels when assessing cardiovascular health risks.

Postnatal leukocytosis reflects the general condition of inflammatory. Infection and inflammatory reaction have been proven to affect the occurrence of ROP and other visual dysfunction. Infants with a gestational age of < 28 weeks who were less than three days of age and admitted to the hospital between September 2015 and March 2021 were included in the study. Infants with a white blood cell (WBC) count ≥ 30 × 109/L were assigned to the leucocytosis group (n = 82). Gestational age- and weight-matched infants without leucocytosis were included as a control group (n = 85). The incidence and prognosis of ROP in preterm infants were compared between the groups. Receiver operating characteristic (ROC) curves were used to analyse the correlation between the WBC count and severe ROP. Compared to the infants in the control group, those in the leucocytosis group had lower 1-min Apgar scores (p < 0.001); higher C-reactive protein (p < 0.001) and procalcitonin (p < 0.001); and higher incidences of intracranial haemorrhage (p = 0.007), leukomalacia (p = 0.045), sepsis (p = 0.006), bronchopulmonary dysplasia (p = 0.017). The maternal age was higher in the leucocytosis group (p < 0.001). After adjusting for gestational age at 45 weeks, the incidence of severe ROP (p = 0.001) and the requirement for ranibizumab injections (p = 0.004) were higher in the leucocytosis group. The cut-off WBC count was determined to be 19.1 × 109/L, with a sensitivity of 88.6%, a specificity of 77.3%, and an area under the curve of 0.941 (95% confidence interval: 0.904-0.978) for the detection of severe ROP. Leucocytosis may be associated with severe ROP in premature infants.

Lymphomatosis cerebri (LC) is a rare type of primary central nervous system lymphoma with diffuse, nonenhancing infiltrative lesions and is often misdiagnosed. Our study aimed to investigate the clinical characteristics and prognosis of LC through analyzing patients from the literature and our own center, so as to improve early diagnosis and treatment. PubMed, Web of Science and our hospital databases were reviewed, and information on demographic, clinical, pathological, cerebrospinal fluid (CSF), neuroimaging and treatment options was extracted. Univariate survival analysis was conducted by generating survival curves and comparing them using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards regression model to identify the prognostic predictors. A total of 81 patients (median age: 58 years; interquartile range, IQR: 50-66.5 years), 45 males and 36 females, were included. The most common symptoms were cognitive impairment (65.4%) and gait impairment (50.6%). Imaging studies indicated that all 81 patients had supratentorial structure involvement, and 93.8% (76/81) had bilateral hemisphere involvement. There were 53.3% (32/60) patients with CSF pleocytosis and 65% (39/60) patients with increased CSF protein levels. The median time of diagnosis was 4.8 months (IQR: 2.3-6.9 months). Compared with 4 (95% CI: 1.78-6.22) months for all 81 patients, the median OS was 20 (95% CI: 8.24-31.76) months for those who had chemotherapy plus radiotherapy. Multivariate Cox analysis revealed that chemoradiotherapy (HR: 0.12; 95% CI: 0.02-0.68) and higher CSF glucose level (HR: 0.01; 95% CI: 0.00-0.26) were inversely associated with death. The diagnosis of LC should be alerted when neuroimaging with bilateral hemispheric involvement and CSF abnormality with pleocytosis and increased protein. Once the diagnosis is confirmed, the combination of chemotherapy and radiotherapy can be considered if the patient\'s physical condition permits.Journal standard instruction requires an unstructured abstract. Kindly check and confirm.We have checked and confirmed that there is no problem.

BACKGROUND: Acute myeloid leukemia (AML) and hyperleukocytosis have an unfavorable prognosis, but the impact of hyperleukocytosis on the prognosis of pediatric AML remains uncertain. We investigated the clinical characteristics and prognosis of pediatric AML with hyperleukocytosis, defined as WBC ≥ 50 × 109/L.
METHODS: A total of 132 patients with newly diagnosed childhood AML with hyperleukocytosis were consecutively enrolled at our center from September 2009 to August 2021 to investigate prognostic factors and clinical outcomes.
RESULTS: Hyperleukocytosis occurred in 27.4% of AML patients. Pediatric patients with hyperleukocytosis had similar CR and OS rates to those without hyperleukocytosis, but had a lower EFS rate. In our study, rates of CR1, mortality, relapsed/refractory disease, and HSCT were comparable between AML patients with WBC counts of 50-100 × 109/L and ≥ 100 × 109/L. AML patients with a WBC count of 50-100 × 109/L had a similar 5-year OS rate to patients with a WBC count ≥ 100 × 109/L (74.6% vs. 75.4%, P = 0.921). Among all patients with hyperleukocytosis, the FAB M5 subtype was associated with significantly inferior survival, and the prognosis of CBF-AML was good.
CONCLUSIONS: Pediatric AML patients with hyperleukocytosis have the similar prognosis regardless of whether their WBC count is 50-100 × 109/L or ≥ 100 × 109/L.

UNASSIGNED: The remarkable effect of arsenic trioxide (ATO) was verified, but side effects are generally observed in acute promyelocytic leukemia (APL) patients, especially leukocytosis and hepatotoxicity. Our aims are to study predictors and reduce ATO-induced side effects without inhibiting efficacy.
UNASSIGNED: Sulfhydryl in ATO-treated APL patients was detected by the Spectra Max M5 microplate reader. And patients were divided into high and low sulfhydryl groups according to median sulfhydryl concentration. The onset time of leukocytosis and the peak value of WBC were compared . Correlations between hepatotoxicity indicators and sulfhydryl concentrations were analysed.
UNASSIGNED: The concentration of sulfhydryl before treatment was significantly higher in the high sulfhydryl group. Leukocytosis ((7.0 ± 5.5) vs. (14.6 ± 8.5) day) and the peak value of WBC occurred earlier in the low sulfhydryl group ((10.8 ± 5.9) vs. (19.3 ± 5.5) day) than in the high group, and the peak value was significantly lower in the low sulfhydryl group ((24.04 ± 15.05) × 109/L) than in the high group ((42.95 ± 25.57) × 109/L). The elevated liver enzymes were smaller in the higher sulfhydryl group between time points before treatment and the treatment one week later (ΔALT 66.57 vs. 9.85 U/L, ΔAST 59.52 vs. 17.76 U/L), as between time points before treatment and peak value. There was a negative correlation between sulfhydryl and elevated liver enzymes.
UNASSIGNED: Higher sulfhydryl compounds contribute to ameliorating ATO-induced leukocytosis and hepatotoxicity in APL patients. The low sulfhydryl before treatment can advance the onset of leukocytosis. For patients with higher sulfhydryl in the early stage, close monitoring of liver enzymes is warranted instead of prophylactic applying any hepatoprotective intervention, to maintain ATO efficacy.

Osteopetrosis is a genetic condition of the skeleton characterized by increased bone density caused by osteoclast formation and function defects. Osteopetrosis is inherited in the form of autosomal dominant and autosomal recessive manner. We report autosomal recessive osteopetrosis (ARO; OMIM 611490) in a Chinese case with a history of scarce leukocytosis, vision and hearing loss, frequent seizures, and severe intellectual and motor disability. Whole-exome sequencing (WES) followed by Sanger sequencing revealed novel compound heterozygous mutations in the chloride channel 7 (CLCN7) gene [c.982-1G > C and c.1208G > A (p. Arg403Gln)] in the affected individual, and subsequent familial segregation showed that each parent had transmitted a mutation. Our results confirmed that mutations in the CLCN7 gene caused ARO in a Chinese family. Additionally, our study expanded the clinical and allelic spectrum of the CLCN7 gene and enhanced the applications of WES technology in determining the etiology of prenatal diagnoses in fetuses with ultrasound anomalies.

Neutropenia is a noteworthy side effect of clozapine, which might warrant this drugs\' discontinuance for safety. Studies have revealed that the risk of neutropenia increases with concurrent administration of valproate, but the evidence was limited. Conversely, lithium may have an ameliorating effect on clozapine-induced neutropenia. This study explored the effects of valproate and lithium on white blood cell counts in patients treated with clozapine.
We retrospectively investigated the electronic medical records from one tertiary psychiatric hospital in Taiwan and enrolled patients discharged between January 1, 2006, and December 31, 2017, with clozapine prescriptions. We scrutinized their demographic data, medications, and hematological results at discharge and during follow-up outpatient clinic visits over the subsequent 3 years. Patients were classified into four groups: clozapine only (CLO), clozapine and valproate (CLO + VAL), clozapine and lithium (CLO + Li), and clozapine, valproate, and lithium (CLO + VAL + Li). We also identified hematological events (neutropenia or leukocytosis) of these patients during outpatient follow-ups.
Of the included 1084 patients, 55(5.1%) developed neutropenia. Concurrent valproate use (odds ratio [OR] = 3.49) and older age (p = .007) were identified as risk factors. Moreover, 453 (41.79%) patients developed leukocytosis. Younger age; male sex; and concurrent use of lithium (OR = 3.39, p < .001), clozapine daily dosage, and benzodiazepines were the risk factors for leukocytosis.
Concurrent valproate use and older age are associated with the development of neutropenia in patients treated with clozapine. Concurrent lithium usage, younger age, male sex, and concurrent benzodiazepine use might be related to leukocytosis.

Published data regarding efficacy of intrauterine perfusion of recombinant human granulocyte colony-stimulating factor for patients with unexplained recurrent spontaneous abortion (URSA) is inconclusive. This study aims at evaluating the efficacy and safety of G-CSF in URSA.
Electronic databases were searched including Cochrane Library, PubMed, Embase, China Biology Medicine disc, China Science and Technology Journal Database, Wanfang Database and China National Knowledge Infrastructure Database (last search was performed on Sep 10th, 2022). A systematic review and meta-analysis was conducted with R-language software. Combined relative risk (RRs), and 95% confidence intervals (CIs) were calculated to estimate efficacy and safety.
Compared with placebo, the efficacy of G-CSF in the treatment of URSA patients was significant in conception rate (RR=1.34, 95%CI: 1.03-1.74, P = 0.028), and was none of significance in live birth rate (RR=1.35, 95%CI: 0.99-1.84, P = 0.06). Subgroup analysis showed that the ovulation-period-medication was the protective factor for conception rate, while \"Ethnicity Asian\" and \"ovulation-period medication\" were the protective factors for live birth rate. When it comes to the safety of rhG-CSF on URSA, meta-analysis showed that rhG-CSF had no significant effect on the incidence of adverse events (AEs) (RR=1.13, 95% CI: 0.89-1.43, P = 0.322), and subgroup analysis showed that the incidence of AEs in each subgroup did not increase significantly (P > 0.05).
Based on our meta-analysis, intrauterine perfusion of rhG-CSF in ovulation period is an effective and safe way to improve conception rate in URSA.