Peripheral Blood Counts Research Articles

Clinicopathologic Analysis of COVID‐19 Associated Thrombi in the Setting of Large Vessel Occlusion: A Prospective Case–Control Study

Background Acute ischemic stroke secondary to large vessel occlusion is among the most serious complications associated with COVID‐19 infection resulting in worse morbidity and mortality. We sought to study the association between COVID‐19 infection and large vessel occlusion thrombus pathology to better define the etiopathogenesis of this atypical cause of stroke. Methods Thrombi were collected during mechanical thrombectomy and stained using hematoxylin and eosin. Blinded analysis of pathology was prospectively performed by a board‐certified neuropathologist. Red blood cell, fibrin, and white blood cell predominance was ascertained. Concomitant peripheral blood counts and clinical and imaging data were collected and analyzed. All samples underwent performance of reverse transcription polymerase chain reaction for SARS‐CoV2. Results Between January 2020 and February 2022, a total of 952 acute ischemic stroke admissions were seen at the University Medical Center of El Paso, TX. Of these, 195 patients (20.5%) had large vessel occlusions and underwent mechanical thrombectomy and 53 patients had thrombus collected and analyzed. Seven patients (3.6%) tested positive for SARS‐CoV2. COVID‐19 positive patients were more likely to be younger (mean 57.4 years; P =0.07), male (85.7%; P =0.03), and have red blood cell predominant thrombi (85.7%; P =0.03). There was a statistically significant association between peripheral neutrophil count and white blood cell lysis in the overall cohort ( P =0.015), who did not differ according to COVID‐19 status. Conclusion Thrombi retrieved from patients who were COVID‐19 positive and had stroke demonstrated red blood cell predominance. This finding requires further investigation using appropriate immunohistochemical techniques in a larger cohort of patients.

Metronomic capecitabine with rapamycin exerts an immunosuppressive effect by inducing ferroptosis of CD4+ T cells after liver transplantation in rat

Liver transplantation is one of the most effective treatments for hepatocellular carcinoma (HCC). The balance between inhibiting immune rejection and preventing tumor recurrence after liver transplantation is the key to determining the long-term prognosis of patients with HCC after liver transplantation. In our previous study, we found that capecitabine (CAP), an effective drug for the treatment of HCC, could exert an immunosuppressive effect after liver transplantation by inducing T cell ferroptosis. Recent studies have shown that ferroptosis is highly associated with autophagy. In this study, we confirmed that the autophagy inducer rapamycin (RAPA) combined with metronomic capecitabine (mCAP) inhibits glutathione peroxidase 4 (GPX4) and promotes ferroptosis in CD4+ T cells to exert immunosuppressive effects after rat liver transplantation. Compared with RAPA or mCAP alone, the combination of RAPA and mCAP could adequately reduce liver injury in rats with acute rejection after transplantation. The CD4+ T cell counts in peripheral blood, spleen, and transplanted liver of recipient rats significantly decreased, and the oxidative stress level and ferrous ion concentration of CD4+ T cells significantly increased in the combination group. In vitro, the combination of drugs significantly promoted autophagy, decreased GPX4 protein expression, and induced ferroptosis in CD4+ T cells. In conclusion, the autophagy inducer RAPA improved the mCAP-induced ferroptosis in CD4+ T cells. Our results support the concept of ferroptosis as an autophagy-dependent cell death and suggest that the combination of ferroptosis inducers and autophagy inducers is a new research direction for improving immunosuppressive regimens after liver transplantation.

Risk factors for portal vein system thrombosis after partial splenic embolisation in cirrhotic patients with hypersplenism

To determine risk factors for portal venous system thrombosis (PVST) after partial splenic artery embolisation (PSAE) in cirrhotic patients with hypersplenism. Between March 2014 and February 2022, 428 cirrhotic patients with hypersplenism underwent partial splenic artery embolisation and from these patients 208 were enrolled and 220 were excluded. Medical records of enrolled patients were collected. Computed tomography (CT) images were reviewed by two blinded, independent radiologists. Statistical analyses were performed by using SPSS. Progressive PVST was observed in 18.75% (39/208) of cirrhotic patients after PSAE. No significant differences in peripheral blood counts, liver function biomarkers, and renal function were observed between the patients with progressive PVST and the patients without progressive PVST. The imaging data showed significant differences in PVST, the diameters of the portal, splenic, and superior mesenteric veins between the progressive PVST group and non-progressive PVST group. Univariate and multivariate analysis demonstrated portal vein thrombosis, spleen infarction percentage, and the diameter of the splenic vein were independent risk factors for progressive PVST. Seventeen of 173 (9.83%) patients showed new PVST; the growth of PVST was observed in 62.86% (22/35) of the patients with pre-existing PVST. Spleen infarction percentage and the diameter of the splenic vein were independent risk factors for new PVST after PSAE. The present study demonstrated portal vein thrombosis, spleen infarction percentage, and the diameter of the splenic vein were independent risk factors for PVST after PSAE in cirrhotic patients with hypersplenism.

Effectiveness and safety of Xuebijing injection for patients with coronavirus disease 2019: a systematic review and Metaanalysis.

To evaluate the effectiveness and safety of Xuebijing injection (XBJ) on coronavirus disease 2019 (COVID-19) in patients. Related studies on multiple biological databases and websites were searched up to December 11, 2021 without language and publication time restrictions. Review Manager V.5.3 and Stata 14 software were used for data analysis. Seven studies were finally included. The Metaanalysis showed that compared with the routine treatment alone, XBJ combined with the routine treatment can reduce the 28day mortality ( = 0.3, 95% : 0.12, 0.74), Creactive protein ( = -12.8, 95% : -23.13, 3.46), erythrocyte sedimentation rate ( = -9.32, 95% : -14.66, -3.98) and interleukin-6 (S = -0.6, 95% : -1.04, -0.17) levels and increase the leukocyte ( = 0.73, 95% : 0.42, 1.04) and lymphocyte count ( = 0.18, 95% : 0.07, 0.29) in peripheral blood; additionally, it has no obvious side effects ( = 1.11, 95% : 0.65, 1.9). There was no evidence that the XBJ combined therapy can improve the nucleic acid conversion rate and computed tomography improvement rate of COVID19 patients. Preliminary evidence suggests that XBJ combined with routine treatment seems to be more effective than routine treatment for patients with COVID19. Limited by the number and quality of included papers, this finding still needs further validation by more studies.

Could the Crosstalk Between Myeloid-Derived-Suppressor Cells and Regulatory T Cells Have a Role in Beta-Thalassemia?

Secondary iron overload, alloimmunization, and increased risk of infection are common complications in patients with transfusion-dependent thalassemia (TDT). Regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) play an essential role in preventing excessive immune response. This research aimed to study the interaction between Tregs and MDSCs in TDT patients and to evaluate the association of these cell types with disease severity. This case-control study included 26 patients with TDT and 23 healthy, age- and sex-matched controls. All patients were investigated for complete blood count (CBC), serum ferritin, and flow cytometric analysis of peripheral blood to detect Tregs, MDSCs, and MDSC subsets. A significant increase was observed in the frequencies of Tregs and MDSCs, particularly monocytic MDSCs (MO-MDSCs), in TDT patients compared with controls. The frequencies of these cells showed a direct association with ferritin level and total leukocyte count and an inverse association with hemoglobin level. Furthermore, a positive correlation was observed between Tregs and each of the total MDSCs and MO-MDSCs. Levels of Tregs and MDSCs increased in TDT and may probably have a role in suppressing the active immune systems of TDT patients.

Partial splenic embolization combined with endoscopic therapies and vasoconstrictive drugs reduces rebleeding in cirrhosis patients with acute variceal bleeding and hypersplenism: a multicenter randomized controlled trial.

This study aimed to compare the efficacy of partial splenic embolization (PSE) combined with endoscopic therapy and endoscopic therapy alone in cirrhosis patients with acute variceal bleeding (AVB) and hypersplenism. Cirrhosis patients with AVB who visited three hospitals from June 2016 to June 2022 were prospectively enrolled and randomly allocated to either the endoscopic therapy combined with PSE group (EP group) or the endoscopic intervention group (E group) in a 1:1 ratio. The primary endpoint of the study was re-bleeding of varices during follow-up, and the secondary endpoints were the recurrence of varices, death, and adverse events. One hundred and fourteen patients were prospectively included, of whom 110 completed the trial. The risk of variceal re-bleeding (19.3% vs. 40.4% (23/57), p = 0.013) and variceal recurrence (28.1% vs. 63.2%, p < 0.001) five years after treatment was significantly lower in the EP group than in the E group, and the EP treatment was the only significant independent risk factor affecting variceal re-bleeding and variceal recurrence in patients. The mortality rate was comparable between the EP and E groups. Peripheral blood counts and liver function all improved significantly in the EP group compared to the E group during the follow-up (p < 0.05). The rates of variceal re-bleeding and recurrence were significantly lower in cirrhosis patients with AVB and hypersplenism after combined endoscopic and PSE treatment compared to those who were provided endoscopic treatment only. The peripheral blood counts and liver function were also improved significantly in EP group (NCT02778425).

Inhaled Maintenance Therapy in the Follow-Up of COPD in Outpatient Respiratory Clinics. Factors Related to Inhaled Corticosteroid Use. EPOCONSUL 2021 Audit

ObjectiveThe aim of this analysis was to describe the patterns of inhaled maintenance therapy according to risk level and to explore the determinants associated with the decision to prescribe inhaled corticosteroids (ICS) in addition to bronchodilator therapy according to risk level as strategy in the follow-up of COPD in daily clinical practice. MethodsEPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021 and January 31, 2022. Results4225 patients from 45 hospitals in Spain were audited. Risk levels were analyzed in 2678 patients. 74.5% of patients were classified as high risk and 25.5% as low risk according to GesEPOC criteria. Factors associated with the prescription of ICS in low-risk COPD were symptoms suggestive of asthma [OR: 6.70 (3.14–14.29), p<0.001], peripheral blood eosinophilia>300mm3 [OR: 2.16 (1.10–4.24), p=0.025], and having a predicted FEV1%<80% [OR: 2.17 (1.15–4.08), p=0.016]. In high-risk COPD, factors associated with triple therapy versus dual bronchodilator therapy were a mMRC dyspnea score of ≥2 [OR: 1.97 (1.41–2.75), p<0.001], symptoms suggestive of asthma [OR: 6.70 (3.14–14.29), p<0.001], and a predicted FEV1%<50% [OR: 3.09 (1.29–7.41), p<0.011]. ConclusionsInhaled therapy in the follow-up of COPD does not always conform to the current guidelines. Few changes in inhaled therapy are made at follow-up visits. The use of ICS is common in COPD patients who meet low-risk criteria in their follow-up and triple therapy in high-risk COPD patients is used as an escalation strategy in patients with high clinical impact. However, a history of exacerbations and eosinophil count in peripheral blood were not factors predicting triple therapy.

Relationship of Ki-67 index in biopsies of metastatic breast cancer tissue and circulating tumor cells (CTCs) at the time of biopsy collection

BackgroundThe proliferation marker Ki-67 is a major pathological feature for the description of the state of disease in breast cancer. It helps to define the molecular subtype and to stratify between therapy regimens in early breast cancer and helps to assess the therapy response. Circulating tumor cells (CTCs) are a negative prognostic biomarker for progression free (PFS) and overall survival (OS) in patients with metastatic breast cancer. Therefore, the CTC count is often described as surrogate for the tumor burden. Both, decrease of Ki-67 and CTC count are considered as evidence for therapy response. The presented work analyzed the correlation between the Ki-67 indices of metastatic tissue biopsies and CTC counts in biopsy time-adjacent peripheral blood samples.Patients and methodsBlood samples from 70 metastatic breast cancer patients were obtained before the start of a new line of systemic therapy. CTCs were enumerated using CellSearch® (Menarini Silicon Biosystems, Bologna, Italy) whereas intact CTCs (iCTCs) and non-intact or apoptotic CTCs (aCTCs) were distinguished using morphologic criteria. The proportion of cells expressing Ki-67 was evaluated using immunohistochemistry on biopsies of metastases obtained concurrently with CTC sampling before the start of a new line of systemic therapy.Results65.7% of patients had a Ki-67 index of > 25%. 28.6% of patients had ≥ 5, 47.1% ≥ 1 iCTCs. 37.1% had ≥ 5, 51.4% ≥ 1 aCTCs. No correlation was shown between Ki-67 index and iCTC and aCTC count (r = 0.05 resp. r = 0.05, Spearman’s correlation index). High CTC-counts did not coincide with high Ki-67 index. High Ki-67, ≥ 5 iCTCs and aCTCs are associated with poor progression free (PFS) and overall survival (OS).ConclusionCTCs and Ki-67 are independent prognostic markers in metastatic breast cancer. High Ki-67 in metastatic tumor tissue is not correlated to high iCTC or aCTC counts in peripheral blood.

Exploring Extended White Blood Cell Parameters for the Evaluation of Sepsis among Patients Admitted to Intensive Care Units.

Sepsis is a major cause of mortality and morbidity in intensive care units. This case-control study aimed to investigate the haematology cell population data and extended inflammatory parameters for sepsis management. The study included three groups of patients: sepsis, non-sepsis, and healthy controls. Patients suspected of having sepsis underwent a Sequential Organ Failure Assessment (SOFA) evaluation and had blood drawn for blood cultures, complete peripheral blood counts (CBC), and measurements of various markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). We observed significant changes in numerous CBC parameters and extended inflammation parameters (EIPs), in addition to significant biochemical analysis markers CRP and IL-6 in sepsis cohorts. Multiple logistic regression analyses showed that combining different CBC parameters and EIPs were effective to profile these patients. Two different models have been developed using white blood cell counts and their extended parameters. Our findings indicate that the absolute counts of white blood cells, and the EIPs which reflect their activation states, are important for the prediction and assessment of sepsis, as the body responds to an insult that triggers an immune response. In an emergency situation, having timely updates on patient conditions becomes crucial for guiding the management process. Identifying trends in these specific patient groups will aid early diagnosis, complementing clinical signs and symptoms, especially as CBC is the most commonly ordered test in a diagnostic workup.

The correlation between peripheral complete blood count parameters and diabetic macular edema in proliferative diabetic retinopathy patients: a cross-sectional study.

Numerous studies have demonstrated that retinal chronic inflammation plays a critical role in the pathogenesis of diabetic macular edema (DME). However, studies about the association between peripheral complete blood count, an inexpensive and easily measurable laboratory index, and DME are limited. The current study was a hospital-based, cross-sectional study. The participants were inpatients with type 2 diabetes who underwent vitrectomy for PDR, and the contralateral eyes in these PDR patients meeting the criteria were included in the study. Central macular thickness (CMT) was measured automatically and the DME was characterized as CMT ≥ 300 μm. A total of 239 PDR participants were enrolled. The average age was 55.46 ± 10.08 years old, and the average CMT was 284.23 ± 122.09 μm. In the fully adjusted model, for CMT, the results revealed a significantly negative association between CMT and both white blood cell (WBC) count and neutrophil count (β = -11.95, 95% CI: -22.08, -1.82; p = 0.0218; β = -14.96, 95% CI: -28.02, -1.90; p = 0.0259, respectively); for DME, the results showed an inverse association between DME and WBC count, monocyte count, and eosinophil count (OR = 0.75, 95% CI: 0.59, 0.95; p = 0.0153; OR = 0.07, 95% CI: 0.00, 0.92; p = 0.0431; OR = 0.03, 95% CI: 0.00, 0.88; p = 0.0420, respectively). In conclusion, our results suggest that WBC and its subtypes in circulation may play an important role in the pathogenesis of DME in PDR patients.

Association between blood eosinophil count and Duchenne muscular dystrophy severity and prognosis: a retrospective cohort study

BackgroundDuchenne muscular dystrophy (DMD) is a rare hereditary muscular disease. The role of eosinophils in DMD has not been clarified. This study aims to evaluate the association between peripheral blood eosinophil count and severity and prognosis of DMD.MethodsA retrospective cohort study was performed for 145 DMD patients between January 2012 and December 2020. Clinical data of 150 healthy children were collected as a control group. Logistic regression and Cox regression analyses were used to explore the influences of eosinophil count on DMD severity and prognosis.ResultsEosinophil count in DMD group was lower than the control group (Z = 2.163, P = 0.031). It was negatively correlated with Vignos scale score, Spearman correlation coefficient was p = 0.245, P = 0.040 (at admission),p = 0.137, P = 0.032 (at follow-up); was a protective factor for high Vignos scale score at admission [odds ratio (OR) = 0.038, 95%CI: 0.002–0.752, P = 0.032] and follow-up (OR = 0.033,95%CI: 0.001–0.121, P = 0.039). The Cox regression analysis indicated that elevated eosinophil count was correlated with better therapeutic efficacy for DMD patients [hazard ratio (HR) = 2.218, 95%CI: 1.154–3.924, P = 0.016].ConclusionEosinophil count in peripheral blood was correlated with the severity of DMD. It could indicate the therapeutic efficacy and prognosis of DMD patients to a certain extent. Eosinophils may be a potentially valuable biomarker or therapeutic target for DMD.

Application and clinical significance of intercellular proximity labeling technique in chronic myelogenous leukemia

Objective: This study aimed to explore the application of interaction-dependent fucosyl-biotinylation (FucoID), a chemical biology-based proximity labeling technique, in capturing tumor antigen-specific T cells and its clinical value in chronic myelogenous leukemia (CML) . Methods: Flow cytometry and fluorescence microscopy were employed to evaluate the experimental parameters for FucoID in CML. Peripheral blood samples were obtained from 14 newly diagnosed CML patients in the chronic phase. These samples underwent flow cytometry-based sorting and were subsequently labeled with FucoID to facilitate the isolation of tumor cells and T cells, followed by the immunophenotypic identification of tumor antigen-specific T cells. Finally, the diagnostic and therapeutic potential of FucoID in CML was assessed. Results: Initially, the experimental parameters for FucoID in CML were established. The proportion of CD3(+) T cells in patients was (8.96±6.47) %, exhibiting a marked decrease compared with that in healthy individuals at (38.89±22.62) %. The proportion of tumor-specific antigen-reactive T cells was (3.34±4.49) %, which demonstrated interpatient variability. In addition, the proportion of tumor-specific antigen-active T cells in CD4(+) T cells was (3.95±1.72) %, which was generally lower than the proportion in CD8(+) T cells at (5.68±2.18) %. Compared with those in tumor-specific antigen-nonreactive T cells, CCR7(-)CD45RA(-) effector memory T cells and CCR7(-)CD45RA(+) effector T cells were highly enriched in tumor-specific antigen-reactive T cells. Moreover, the intensity of tumor immune reactivity in patients exhibited a significant correlation with white blood cell count (WBC) and hemoglobin (HGB) levels in peripheral blood, while no such correlation was observed with other clinical baseline characteristics. Conclusion: The combination of FucoID and flow cytometry enables the rapid identification and isolation of tumor antigen-specific T cells in CML. The successful application of this method in CML and the implications of our findings suggest its potential clinical value in the field of hematologic malignancies.

Number of natural killer cells and cytokine levels in peripheral blood at various degrees of severity

This study aims to investigate NK cell number and cytokines level in various degrees of severity in COVID-19 cases. A total of 63 COVID-19 patient aged &gt;18 y were divided into mild-moderate and severe-critical groups. Patient characteristics and peripheral blood count were obtained from medical records. NK cells number, levels of IFN-?, IL-10, and IL-12 in peripheral blood were examined by means of flow cytometry. The severe-critical group had leukocytosis, neutrophilia, lymphopenia, higher Neutrophil Lymphocyte Ratio, lower NK cell number and higher level of IL-10. In severe-critical group, those aged &gt;60 years had higher IL-10. In both groups, patients with diabetes comorbidities had a higher number of NK cells (p&lt;0.05). NK cell number and IL-10 in peripheral blood have potential as a predictor of severe COVID-19 patients.

Peripheral Blood Absolute Lymphocyte Count as a Predictor of Cytomegalovirus Infection in Kidney Transplant Recipients

Cytomegalovirus viremia and infection have been reported to increase the risks for acute graft rejection and mortality in kidney transplant recipients. Previous studies demonstrated that a lower absolute lymphocyte count in peripheral blood is associated with cytomegalovirus infection. The aim of this study was to investigate whether absolute lymphocyte count could predict cytomegalovirus infection in kidney transplant recipients. From January 2010 to October 2021, 48 living kidney transplant recipients in whom both donor and recipient were positive for immunoglobulin G of cytomegalovirus were included in this retrospective study. The primary outcome was defined as cytomegalovirus infection occurring ≥28 days after kidney transplantation. All recipients were followed for 1 year after kidney transplantation. The diagnostic accuracy of absolute lymphocyte count on day 28 post-transplantation for cytomegalovirus infection was analyzed using receiver operating characteristic curves. A Cox proportional hazards model was used to calculate hazard ratios for the incidence of cytomegalovirus infection. There were 13 patients (27%) with cytomegalovirus infection. The sensitivity and specificity for cytomegalovirus infection were 62% and 71%, respectively; the negative predictive value was 83% when an absolute lymphocyte count of 1100 cells/μL on day 28 post-transplantation was used as the cutoff. The incidence of cytomegalovirus infection was significantly higher when the absolute lymphocyte count was <1100 cells/μL on day 28 post-transplantation (hazard ratio, 3.32; 95% CI, 1.08-10.2). Absolute lymphocyte count is an inexpensive and easy test that can effectively predict cytomegalovirus infection. Further validation is needed to confirm its utility.

Association of Myelofibrosis Phenotypes with Clinical Manifestations, Molecular Profiles, and Treatments.

Myelofibrosis (MF) presents an array of clinical manifestations and molecular profiles. The two distinct phenotypes- myeloproliferative and myelodepletive or cytopenic- are situated at the two poles of the disease spectrum and are largely defined by different degrees of cytopenias, splenomegaly, and distinct molecular profiles. The myeloproliferative phenotype is characterized by normal/higher peripheral blood counts or mildly decreased hemoglobin, progressive splenomegaly, and constitutional symptoms. The myeloproliferative phenotype is typically associated with secondary MF, higher JAK2 V617F burden, fewer mutations, and superior overall survival (OS). The myelodepletive phenotype is usually associated with primary MF, ≥2 cytopenias, modest splenomegaly, lower JAK2 V617F burden, higher fibrosis, greater genomic complexity, and inferior OS. Cytopenias are associated with mutations in epigenetic regulators/splicing factors, clonal evolution, disease progression, and shorter OS. Clinical variables, in conjunction with the molecular profiles, inform integrated prognostication and disease management. Ruxolitinib/fedratinib and pacritinib/momelotinib may be more suitable to treat patients with the myeloproliferative and myelodepletive phenotypes, respectively. Appreciation of MF heterogeneity and two distinct phenotypes, the different clinical manifestations and molecular profiles associated with each phenotype alongside the growing treatment expertise, the development of non-myelosuppressive JAK inhibitors, and integrated prognostication are leading to a new era in patient management. Physicians can increasingly tailor personalized treatments that will address the unique unmet needs of MF patients, including those presenting with the myelodepletive phenotype, to elicit optimal outcomes and extended OS across the disease spectrum.

The genetic polymorphisms of immune-related genes contribute to the susceptibility and survival of lymphoma.

Though immunological abnormalities have been proven involved in the pathogenesis of lymphoma, the underlying mechanism remains unclear. We investigated 25 single nucleotide polymorphisms (SNPs) of 21 immune-related genes and explored their roles in lymphoma. The genotyping assay of the selected SNPs was used by the Massarray platform. Logistic regression and Cox proportional hazards models were used to analyze the associations of SNPs and the susceptibility of lymphoma or clinical characteristics of lymphoma patients. In addition, Least Absolute Shrinkage and Selection Operator regression was used to further analyze the relationships with the survival of lymphoma patients and candidate SNPs, and the significant difference between genotypes was verified by the expression of RNA. By comparing 245 lymphoma patients with 213 healthy controls, we found eight important SNPs related to the susceptibility of lymphoma, which were involved in JAK-STAT, NF-κB and other functional pathways. We further analyzed the relationships between SNPs and clinical characteristics. Our results showed that both IL6R (rs2228145) and STAT5B (rs6503691) significantly contributed to the Ann Arbor stages of lymphoma. And the STAT3 (rs744166), IL2 (rs2069762), IL10 (rs1800871), and PARP1 (rs907187) manifested a significant relationship with the peripheral blood counts in lymphoma patients. More importantly, the IFNG (rs2069718) and IL12A (rs6887695) were associated with the overall survival (OS) of lymphoma patients remarkably, and the adverse effects of GC genotypes could not be offset by Bonferroni correction for multiple comparison in rs6887695 especially. Moreover, we determined that the mRNA expression levels of IFNG and IL12A were significantly decreased in patients with shorter-OS genotypes. We used multiple methods of analysis to predict the correlations between lymphoma susceptibility, clinical characteristics or OS with SNPs. Our findings reveal that immune-related genetic polymorphisms contribute to the prognosis and treatment of lymphoma, which may serve as promising predictive targets.

Correlation between hyperbilirubinemia risk and immune cell mitochondria parameters in neonates with jaundice.

To explore the correlation between mitochondria parameters of immune cells and hyperbilirubinemia risk in hospitalized neonates with jaundice. This retrospective study included jaundiced neonates born between September 2020 and March 2022 at Shaoxing Keqiao Women & Children's Hospital. The neonates were divided into low, intermediate-low, intermediate-high, and high-risk groups according to the hyperbilirubinemia risk. The purpose parameters including percentage, absolute count, mitochondrial mass (MM), and single-cell MM (SCMM) of peripheral blood T lymphocytes detected by flow cytometry were collected. Finally, 162 neonates with jaundice (47, 41, 39, and 35 with low, intermediate-low, intermediate-high, and high-risk) were included. CD3+ SCMM was significantly higher in the high-risk group compared with the low and intermediate-low-risk groups (both P < 0.0083), CD4+ SCMM was significantly higher in the high-risk group compared with the three other groups (all P < 0.0083), and CD8+ SCMM was significantly higher in the intermediate-low and high-risk groups compared with the low-risk group (both P < 0.0083). CD3+ (r = 0.34, P < 0.001) and CD4+ (r = 0.20, P = 0.010) SCMM positively correlated with bilirubin levels. The mitochondrial SCMM parameters differed significantly among jaundiced neonates with different hyperbilirubinemia risks. CD3+ and CD4+ T cell SCMM values were positively correlated with the serum bilirubin levels, and might correlated with hyperbilirubinemia risk.

Clinical features, laboratory characteristics, and outcome of ETP and TCRA/D aberrations in pediatric patients with T-acute lymphoblastic leukemia

BackgroundT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy with few accepted prognostic factors that limit the efficiency of therapy. The aim of the current study was to assess the clinical and laboratory features of T-cell receptor (TCR) aberrations and early T-cell precursor (ETP) subtype as well as their outcome to therapy.MethodsSixty-three newly diagnosed pediatric T-ALL patients were assessed for the ETP status using immunophenotyping. Screening of TCRA/D aberrations was done by fluorescent in situ hybridization (FISH). The data were correlated to the patients’ clinical features, response to treatment, and survival rates.ResultsSeven patients (11%) had ETP-ALL. The ETP-ALL patients were older (P = 0.013), presented with lower white blood cell (WBC) count (P = 0.001) and lower percentage of peripheral blood (PB) blast cells (P = 0.037), more likely to have hyperdiploid karyotype (P = 0.009), and had been associated with TCRA/D gene amplification (P = 0.014) compared to other T-ALL patients. Of note, the same associations had been significantly observed in patients with TCRA/D gene amplification. Patients with TCRA/D amplification frequently coincided with TCRβ aberrations (P = 0.025). TCR-β aberrations were significantly associated with negative MRD at the end of induction compared to TCR-β-negative patients. There was a nonsignificant trend of ETP-positive cases to have lower overall survival (OS) (P = 0.06). Patients with TCR aberrations had no significant differences regarding disease-free survival (DFS) or OS rates compared to those with normal TCR.ConclusionETP-ALL patients tend to have increased mortalities. There was no significant impact of TCR aberrations on the survival rates of the patients.

Systematic Evaluation of Hematologic Parameters and Blood Smear Findings in Patients With SARS-CoV-2 vs Other Viral Respiratory Infections.

We evaluated and compared the peripheral blood findings in patients with acute COVID-19 vs other viral respiratory infections. We retrospectively reviewed peripheral blood counts and smear morphology in patients with a positive viral respiratory panel (VRP) or SARS-CoV-2 test. A total of 97 peripheral blood samples (COVID-19 infection, 53; VRP positive, 44) from 50 patients (mean [SD] age, 45.8 [20.8] years; females 52%) were reviewed. There were no statistically significant differences in the demographic characteristics between the 2 groups. The most common peripheral blood abnormalities were anemia, thrombocytopenia, absolute lymphopenia, and reactive lymphocytes. The following peripheral blood findings were significantly associated with other viral respiratory infections compared with COVID-19 infection: low red blood cell count, low hematocrit, high mean corpuscular volume, thrombocytopenia, low mean platelet volume, high red cell distribution width, band neutrophilia, and toxic granulation in neutrophils. Our study showed that there are several peripheral blood count and morphologic abnormalities seen in patients with COVID-19, but most of these findings lack specificity as they are also seen in the other viral respiratory infections.

Association of myeloid-derived suppressor cells with hematopoietic recovery after high-dose chemotherapy in multiple myeloma

Myeloid-derived suppressor cells (MDSCs) play an important role in the immune response regulation in many pathologies, primarily in malignant tumors, but their role in the hematopoietic stem cell engraftment and the hematopoietic recovery after high-dose chemotherapy and autologous stem cell transplantation remains practically unexplored. This study is aimed at studying the correlation between the number of MDSC subpopulations and blood parameters at the stage of hematopoietic recovery after high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with multiple myeloma (MM). Circulating MDSCs were assessed at the stage of leukopenia recovery (absolute leukocyte count in peripheral blood (PB) &gt; 1 x 109/L) by flow cytometry. The number of transplanted CD34+CD45+ hematopoietic stem cells was 4.38 x 106/kg (IQR (3.1—5.6) x 106/kg). The duration of recovery from leukopenia varied from 8 to 18 days (Me 12 days). The number of MDSCs at the engraftment was not associated with the number of CD34+ cells/kg in the graft. The relative number of monocytic MDSCs (M-MDSCs, CD14+HLA-DRlow/-) directly correlated with the number of monocytes at the stage of recovery from leukopenia (R = 0.417, p = 0.002). Granulocytic MDSCs (PMN-MDSCs, Lin-HLA-DR-CD33+CD66b+) were characterized by an inverse correlation with the number of monocytes (R = -0.493, p = 0.0003) while the association with the absolute number of neutrophils was weak (R = 0.273, p = 0.048). The number of lymphocytes at the stage of recovery from leukopenia had an inverse correlation with PMN-MDSCs (R = -0.347, p = 0.014) and did not correlate with M-MDSCs. When analyzing the duration of leukopenia, an inverse correlation with this indicator was revealed for the percentage and absolute number of M-MDSCs (R = -0.347, p = 0.018 and R = -0.469, p = 0.0008, respectively). Multiple regression analysis showed dependence of the lymphopenia duration on the proportion of circulating M-MDSCs (p = 0.014) and the number of transplanted CD34+ cells/kg (p = 0.032). According to the data of multivariate analysis of variance, the number of transplanted CD34+ cells/kg and the number of M-MDSCs were significant factors for the duration of leukopenia. At the same time, such clinical parameters as the depth of response and minimal residual disease status before high-dose chemotherapy and hematopoietic stem cell transplantation, as well as the MM stage, did not affect the duration of hematopoietic recovery. Thus, the obtained results indicate the association of a higher number of M-MDSCs with a shorter duration of leukopenia after high-dose chemotherapy with autologous stem cell transplantation and indicate a positive role of M-MDSCs in hematopoietic recovery in the early post-transplant period in patients with MM.