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Abstract. Because its secretion is changed in cerebrospinal fluid and peripheral blood, the neuronal polypeptide VGF (nonacronymic) has been discussed as a biomarker for neuropsychiatric disorders. We have shown an enhanced VGF expression by T-cells from Alzheimer’s disease (AD) patients. In this study, we investigated the VGF expression by peripheral monocytes in 38 AD patients, 5 patients with vascular dementia (VD), and 20 neuropsychiatrically healthy individuals using flow cytometry. We determined an enhanced number of VGF-expressing monocytes in VD patients compared to AD patients. VGF+CD14+ monocytes were not correlated with age, body mass index, Mini-Mental State Examination (MMSE), or Q albumin. These preliminary data support findings indicating that VGF might play a role as a peripheral biomarker in VD.

Micromegakaryocytes (MMGKs), a common finding in bone marrow, have been rarely described in peripheral blood (PB). MMGKs are known to occur commonly in PB of patients diagnosed with Chronic Myeloid Leukemia (CML).[1][1] A characteristic of chronic phase of CML, they are considered to be dysplastic

Background and Aims Clostridioides difficile infection (CDI) is associated with a range of outcomes and existing prediction models for death among patients with CDI are imprecise. Peripheral eosinopenia has been proposed as a novel risk factor for death among patients with CDI but has not been incorporated into prediction models. This study aimed to develop and validate a prediction model for death among patients hospitalized with CDI that incorporated peripheral eosinopenia. Methods Eosinopenia was defined as 0 eosinophils/uL on the soonest peripheral blood draw within the 48-hour window of the CDI test (before or after). Adults were eligible for the study if they were hospitalized at any one of three large, unaffiliated hospital networks, tested positive for CDI by stool PCR and received appropriate anti-CDI treatment. Patients were followed for all-cause death for up to 30 days. Results There were 4,518 unique hospitalized adults with CDI included (2,142 derivation cohort and 2,376 validation cohort). All-cause 30-day mortality was 9% and 10% in the cohorts respectively. In the validation cohort, the factors most strongly associated with death were eosinopenia [adjusted OR (aOR) 2.49, 95% CI 1.77-3.50], albumin 1.5 mg/dL (aOR 2.55, 95% CI 1.86-3.49). A six variable clinical prediction model was developed that improved upon existing classification schemes for CDI severity (AUROC of 0.75 vs. 0.68). Conclusions Among adults hospitalized with CDI, peripheral eosinopenia was associated with increased risk of all-cause 30-day mortality. A prediction model incorporating peripheral eosinopenia was developed to improve care for hospitalized patients with CDI through risk stratification.

The effect of chronic graft-versus-host disease (cGVHD) on the risk of nonrelapse mortality (NRM) and relapse has not been specifically studied in older adults, who are increasingly undergoing allogeneic hematopoietic cell transplantation (alloHCT) and surviving long-term to develop cGVHD. In this Center for International Blood and Marrow Transplant Research (CIBMTR) analysis, we tested our hypothesis that the risk of NRM was higher with the development of cGVHD, particularly among older adults (age ≥60 years). We included 4429 adults age ≥40 years who underwent a first HLA-matched peripheral blood stem cell alloHCT for acute myelogenous leukemia or myelodysplastic syndrome between 2008 and 2017. We compared outcomes of 4 groups—older adults (≥60 years) and younger adults (40 to 59 years) with cGVHD and older and younger adults without cGVHD—to determine the effect of older age and cGVHD on various outcomes. We used Cox proportional hazard models to determine the risk of NRM, relapse, and overall survival (OS). We treated cGVHD as a time-dependent covariate. The severity of cGVHD was based on the CIBMTR clinical definitions. cGVHD was significantly associated with a higher risk of NRM and lower risk of relapse regardless of age. The risk of NRM was higher for older adults versus younger adults. Adults who developed cGVHD as a group had longer OS compared with age-matched cohorts without cGVHD. Older adults had worse OS regardless of cGVHD. Among adults with cGVHD, clinically moderate or severe cGVHD was associated with a significantly higher risk of NRM and lower risk of relapse; severe cGVHD was associated with shorter OS, whereas mild to moderate cGVHD was associated with longer OS. Among both younger and older adults, the development of cGVHD was associated with a higher risk of NRM, lower risk of relapse, and longer OS. Older adults had a higher risk of NRM, but the increased risk of NRM associated with cGVHD did not differ based on age. The development of mild to moderate cGVHD offered the most favorable balance between minimizing NRM and decreasing the risk of relapse. The relapse risk was lowest for adults with severe cGVHD, but high NRM resulted in shorter OS. Developing strategies to avoid clinically severe cGVHD is critically important. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Introduction: Accurate platelet count (PLTC) in immune thrombocytopenia is important in order to make therapeutic decisions. The basic method of assessing PLTC is peripheral blood morphology with EDTA or with citrate. The older way of assessing PLTC is measurement under the microscope (FONIO), and the newer way is the fluorescent method. The purpose of this study was to compare PLTC methods, and find the most reliable. Material and methods: PLTC was assessed using five methods in adult patients with previously untreated ITP (EDTA, citrate, FONIO, fluorescent, and immunofluorescent methods). Results: 66 patients were enrolled in the study. The median age was 56 and 56% were men. Median PLTC in EDTA was 69 G/L, in citrate 69 G/L, in fluorescence 69 G/L, in FONIO 90 G/L, and in immunofluorescence 83 G/L. A significant difference in PLTC was observed in comparing EDTA to immunofluorescence (53% ±123%), followed by FONIO (51% ±91%). PLTC from immunofluorescence differed from the fluorescent method by 40% ±78%. Conclusions: The most valuable method for obtaining PLTC is the immunofluorescent method. These findings are especially important in helping to make therapeutic decisions during a challenging time for accessing medical care like a pandemic.

Among the recently described subtypes in childhood B-lymphoblastic leukemia (B-ALL) were DUX4- and PAX5-altered (PAX5alt). By using whole transcriptome RNA sequencing in 377 children with B-ALL from the Malaysia-Singapore ALL 2003 (MS2003) and Malaysia-Singapore ALL 2010 (MS2010) studies, we found that, after hyperdiploid and ETV6-RUNX1, the third and fourth most common subtypes were DUX4 (n = 51; 14%) and PAX5alt (n = 36; 10%). DUX4 also formed the largest genetic subtype among patients with poor day-33 minimal residual disease (MRD; n = 12 of 44). But despite the poor MRD, outcome of DUX4 B-ALL was excellent (5-year cumulative risk of relapse [CIR], 8.9%; 95% confidence interval [CI], 2.8%-19.5% and 5-year overall survival, 97.8%; 95% CI, 85.3%-99.7%). In MS2003, 21% of patients with DUX4 B-ALL had poor peripheral blood response to prednisolone at day 8, higher than other subtypes (8%; P = .03). In MS2010, with vincristine at day 1, no day-8 poor peripheral blood response was observed in the DUX4 subtype (P = .03). The PAX5alt group had an intermediate risk of relapse (5-year CIR, 18.1%) but when IKZF1 was not deleted, outcome was excellent with no relapse among 23 patients. Compared with MS2003, outcome of PAX5alt B-ALL with IKZF1 codeletion was improved by treatment intensification in MS2010 (5-year CIR, 80.0% vs 0%; P = .05). In conclusion, despite its poor initial response, DUX4 B-ALL had a favorable overall outcome, and the prognosis of PAX5alt was strongly dependent on IKZF1 codeletion.

Computed tomography (CT) is a main contributor to artificial low-dose exposure. Understanding the biological effects induced by CT exposure and their dependency on the characteristics of photon spectra is essential for knowledge-driven risk assessment. In a previous gene expression study, we have identified upregulation of AEN, BAX, DDB2, EDA2R and FDXR after ex vivo exposure with single-energy CT and dual-energy CT (DECT). In this study, we focused on CT-induced changes of DNA methylation. This epigenetic modification of DNA is a central regulator of gene expression and instrumental in preserving genome integrity. Previous studies reported focal hypermethylation and global hypomethylation after exposure with doses above 100 mSv, however, the effect of low dose exposure on DNA methylation is hardly explored. DNA was isolated from peripheral blood of three healthy individuals 6 h after ex vivo exposition to single-energy (80 kV and 150 kV) and DECT (80 kV/Sn150 kV) with a calculated effective dose of 7.0 ± 0.08 mSv. The experimental setting was identical to the one used in our previous gene expression study enabling a direct comparison of gene expression results with changes of DNA methylation identified in this study. DNA methylation was analyzed by high-throughput sequencing of bisulfite-treated DNA targeted methylation sequencing. Unsupervised hierarchical clustering based on DNA methylation profiles of all samples created three distinct clusters. Formation of these three clusters was solely determined by the origin of samples, indicating the absence of prominent irradiation-associated changes of DNA methylation. In line with this observation, inter-individual comparison of non-irradiated samples revealed 1163, 1224 and 4550 significant differentially methylated regions (DMRs), respectively, whereas the pairwise comparison of irradiated and non-irradiated samples failed to identify irradiation-induced DMRs in any of the three probands. This even applied to the genomic regions harboring AEN, BAX, DDB2, EDA2R and FDXR, the five genes known to be upregulated by CT exposure. CT exposure with various photon spectra did not result in detectable changes of DNA methylation. However, minor effects in a subpopulation of irradiated cells cannot be ruled out. Thus, future studies with extended observation intervals are needed to investigate DNA methylation changes that are induced by indirect effects at later points of time or become detectable by clonal expansion of affected cells. Moreover, our data suggest that DNA methylation analysis is less sensitive in detecting immediate effects of low-dose irradiation when compared to gene expression analysis.

Определение клеточной гибели методом проточной цитометрии широко распространено в со-временной диагностике, однако недостаточно изучено применительно к сахарному диабету (СД) 2-го типа.Цель: оценить гибель клеток периферической крови, распределение по клеточному циклу и уровень микроядер методом проточной цитометрии у пациентов с СД 2-го типа при наличии и отсутствии дистальной сенсомоторной нейропатии.Материалы и методы. Обследовано 176 пациентов с СД 2-го типа и 67 относительно здоровых лиц. В обеих группах были определены гибель лейкоцитов периферической крови, клетки с микроядрами и характер распределения клеток по клеточному циклу методом проточной цитометрии. Пациенты с СД 2-го типа были обследованы с целью диагностики диабетической сенсомоторной периферической полинейропатии (ДПНП). Степень тяжести ДПНП оценивалась с помощью общей шкалы неврологических симптомов (Total Symptoms Score — TSS), шкалы нейропатического дисфункционального счета (Neuropathy Disability Score — NDS) и по данным электромиографии. Показатели клеточной гибели в группе пациентов с СД 2-го типа дополнительно анализировались относительно возраста обследуемых, длительности заболевания и степени компенсации. Для анализа использовался пакет программ Statistica 10.Результаты. Обнаружена прямая корреляционная связь между процентом клеток с признаками апоптоза и процентом клеток с микроядрами, что позволяет использовать оба показателя в качестве диагностического критерия единых патологических изменений в организме. Статистически достоверные различия по клеточной гибели обнаружены при сравнении групп с длительностью СД до 10 лет и 10 лет и более. Также обнаружена прямая корреляционная связь между процентом клеток с признаками апоптоза и длительности СД.Выводы. Уровень апоптоза лейкоцитов периферической крови и количество клеток с микроядрами нарастает при увеличении длительности СД 2-го типа независимо от наличия или отсутствия диабетической дистальной полинейропатии, а также компенсации СД, возраста пациента. Определение апоптоза и проведение микроядерного теста лейкоцитов периферической крови могут служить интегральным маркером патологических изменений в организме при СД 2-го типа, но не при диабетической полинейропатии. Распределение клеток периферической крови по клеточному циклу у пациентов с СД 2-го типа существенным образом не зависит от наличия или отсутствия полинейропатии.

BACKGROUND Reduced sensitivity of tuberculosis (TB) interferon-γ release assays (IGRAs) among the elderly has been reported, which is presumably due to diminished immune function. We evaluated the clinical performance of QuantiFERON®-TB Gold plus (QFT-Plus) compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) and T-Spot®.TB (T-SPOT) in the elderly. METHODS Blood samples for all three IGRAs were drawn at the same time from all the participants. Both CD4 and CD8 T-cell counts in patients' peripheral blood were also measured. RESULTS A total of 142 active pulmonary TB patients (median age: 84, interquartile range; 76-89 years) were recruited. The sensitivities of the tested IGRAs (excluding invalid/indeterminate cases) were as follows: QFT-Plus, 93.6%; QFT-GIT, 91.4%; and T-SPOT 68.1%. QFT-Plus displayed significantly higher sensitivity than T-SPOT (p

BACKGROUND: Peripheral blood-based biomarkers (PBB) predicting response, survival and immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate. Thus, we investigated the associations between PBB, the efficacy of ICIs and the incidence of irAEs. METHODS: Patients with advanced NSCLC, who had been treated at Peking Union Medical College Hospital and received ICIs or chemoimmunotherapy from January 2015 to December 2020, were retrospectively identified. PBBs results were retrieved from medical records. Associations with overall response rate, survival, and incidence of irAEs were assessed using Kruskal-Wallis, Kaplan-Meier analysis, Pearson’s chi-squared and Student’s t-tests as required. Cox proportional hazards and logistic regression models were used to determine independent risk factors. Analyses were performed on the whole population (n=103), patients receiving ICIs only (n=32), and patients receiving chemoimmunotherapy (n=71). Changes in pretreatment and on-treatment PBB were also analyzed. RESULTS: Among 103 patients, 38 (36.9%) developed irAEs. Pretreatment absolute lymphocyte count (ALC) was related to an increased risk of irAEs in the whole population [odds ratio (OR), 2.165; 95% confidence interval (CI): 1.040 to 4.509, P=0.039] and patients receiving ICIs only (OR, 6.461; 95% CI: 1.067 to 39.112; P=0.042). A low prognostic nutritional index (PNI ≤45) was associated with worse progression-free survival (PFS) and overall survival (OS) in the whole population, in patients receiving ICIs only, and in patients receiving chemoimmunotherapy. High pretreatment interleukin (IL)-6 was associated with both worse PFS and OS in the whole population (IL-6 >13.80 pg/mL), in patients receiving ICIs only (IL-6 >11.30 pg/mL), and in patients receiving chemoimmunotherapy (IL-6 >11.85 pg/mL). Increase of IL-6 during treatment was associated with inferior OS in the whole population (P

Background: At present, the diagnosis of lymphoproliferative disorders is based on the combination of blood or bone marrow smear morphology and immunophenotyping by flow cytometry. Immunophenotypic testing by flow cytometry technique is available only in big medical centers, which is not always convenient for a patient. Therefore, development of an available method for preliminary diagnosis of lymphoproliferative diseases not requiring special equipment seems relevant.Materials and methods: Peripheral blood mononuclear cells from 17 patients admitted to the hospital with suspicion of a lymphoproliferative disorder, and 17 healthy donors were studied on a cell biochip for determination of proportions of cells positive for various surface CD antigens. The diagnosis was verified by flow cytometry.Results: Compared to healthy controls and patients with T-cell lymphoproliferative disorders (TCLPD), the patients with B-cell lymphoproliferative disorders (BCLPD) had significantly lower proportion of CD7+ cells (medians, 7% and 73% respectively, p=2×10-6 for comparison with healthy controls; median 7% and 93% for comparison with TCLPD, p=0.032). In addition, the patients with BCLPD had higher proportion of peripheral СD19+ mononuclear cells, compared to that in the patients with TCLPD and healthy donors (medians 84% and 13% for comparison between BCLPD and healthy control, p=2×10-5; 84% and 3% for comparison of BCLPD and TCLPD, p=0.033). The patients with B-cell chronic lymphocytic leukemia had significantly higher CD5+ cells in the cell biochip compared to the patients with other BCLPD (medians 72% and 9%, p=0.024). The patients with TCLPD had significantly lower proportion of CD19+ cells than the healthy controls (medians, 3% and 13%, respectively, р=0.042).Conclusion: The study has demonstrated the potential to use the previously developed cell biochip for diagnosis of lymphoproliferative diseases. The biochip makes it possible to sort out white blood cells according to their surface differentiation antigen for their further morphological analysis. The cell biochip allows for the differential diagnosis between BCLPD and TCLPD and determination the lymphocyte clones based on the expression of immunoglobulin light chains.

Background. To enhance the antitumor immune response, new promising methods of immunotherapy are being developed. They consist in the blockade and activation of immune check-point molecules, in particular, the blockade of the Lag‐3 molecule (lymphocyte-activation gene 3) and the activation of the GITR receptor (Glucocorticoid induced TNF receptor). In the studies of combined use with PD-1 blockers, encouraging results were obtained, which makes the assessment of the expression of Lag-3 and GITR on immunocompetent cells of peripheral blood (PB) and tumor tissue necessary for the personalization of such treatment and understanding of the mechanisms of the antitumor immune response. Materials and methods. The study included peripheral blood samples and surgical material from 39 breast cancer patients being treated at the Blokhin National Medical Research Center of Oncology. The subpopulation composition and expression of PD-1, Lag-3, and GITR molecules were evaluated by flow cytometry. Results. The analysis of the main populations of PB lymphocytes showed that in patients with breast cancer, the content of NKT-lymphocytes was increased, and the proportions of lymphocytes expressing CD11b and CD25 markers were increased compared to the donor group. It was revealed that the tumor tissue is dominated by T-cells, an increase in the proportion of which occurs due to a reduced content of NK-lymphocytes and B-lymphocytes. The structure of Tumor-infiltrating lymphocytes (TILs) is dominated by subpopulations with immunosuppressive activity, which is indicated by a decrease in the content of CD11b+, CD25+ and perforin-positive cells, increased expression of Lag-3 and PD-1. For PB and tumor tissue, the average degree of dependence of Lag-3 expression on the content of PD-1+ lymphocytes was shown. There is an increase in the content of immunosuppressive subpopulations with high PD-1 values in PB and TILs. The direct dependence of the number of perforin-containing lymphocytes and CD11b expression on the GITR content in the PB was established, but it is not typical for breast cancer tissue. Conclusion. Since the blockade of the Lag-3 molecule by monoclonal antibodies can enhance the effect of anti-PD-1 therapy in cancer patients, it is necessary to evaluate the expression and co-expression of these two markers. A high content of GITR-positive lymphocytes in the tumor tissue, on the one hand, and a decrease in the proportion of effector subpopulations of lymphocytes, on the other, indicates the influence of the tumor microenvironment on the functioning of GITR-mediated activation of the immune response. Further investigation of GITR expression and functional activity is required to understand the nature of this contradiction.

Due to the evolving use of haploidentical donor grafts in hematopoietic cell transplantation, there is increased need to better understand the risks and benefits of using bone marrow versus peripheral blood grafts, as well as how specific pre-transplantation conditioning regimens impact patient safety and treatment outcomes. We performed a retrospective analysis of 38 patients at two centers who underwent haploidentical hematopoietic cell transplantation using fludarabine plus melphalan-based conditioning regimens with post-transplant cyclophosphamide and peripheral blood donor grafts. We observed an unexpectedly high rate of early non-relapse mortality and severe cytokine release syndrome. The poor outcomes with 1-year overall survival of 34%, disease-free survival of 29%, and non-relapse mortality of 34% motivate us to reconsider the appropriateness of the combination of fludarabine and melphalan conditioning with T-cell replete peripheral blood grafts in the setting of haploidentical hematopoietic cell transplant with post-transplant cyclophosphamide.

The action of checkpoint inhibitors is based on activation of T cell antitumor immunity, and, therefore, the search for markers of lymphocyte functional activity before starting the therapy is highly relevant. Determination of the PD-L1 expression in tumor tissues reflects immunosuppressive activity of malignant cells, and it is used as a predictive marker in clinical practice. The ratio of neutrophils to lymphocytes in tumor tissue and in peripheral blood can also indicate the activity of adaptive immunity and correlates with the efficacy of therapy. It has been shown that a high level of interleukin 1 beta in the tumor microenvironment is associated with immunosuppression of lymphocytes and, possibly, reflects the activity of the tumor microenvironment. The aim of this work is to study the relationship between tumor expression of PD-L1, the concentration of serum interleukin-1 beta and the ratio of neutrophils and lymphocytes in peripheral blood.Before starting therapy with checkpoint inhibitors in patients with various solid tumors (n = 50), the serum level of interleukin-1 beta was determined by ELISA (ELISA-Best, Novosibirsk, Russia), expression of PD-L1 in the tumor by immunohistochemical method, complete blood count was performed using cytometry. Statistical analysis was performed in GraphPad Prism 6 (Graph Pad Software, USA) using the statistical methods of Fisher, Mann-Whitney, and Spearman.The average value of the index of the ratio of neutrophils and lymphocytes (NLR) in peripheral blood was 2.65± 0.21 (95% CI 2.22-3.07). The index value of more than 3.5 was found in 18% (9/50) of patients. The mean value of the PD-L1 expression level was 23.02±4.52% (95% CI 13.86-32.18). Expression of PD-L1 in tumor tissue was detected in 60.1% (25/40) of patients, among whom an increased expression of more than 50% was detected in 20.0% (5/25) of cases. A positive weak correlation was found between the concentration of interleukin 1 beta and the number of leukocytes (r = 0.34; p = 0.019) and index (r = 0.32; p = 0.029). The level of PD-L1 expression in tumor tissue also had a weak positive correlation with the serum interleukin 1 beta concentration (r = 0.33; p = 0.037) and the neutrophil-lymphocyte ratio (r = 0.33; p = 0.034). In the group of patients with PD-L1 expression > 5%, the mean value of the concentration of interleukin 1 beta was 1.65±0.62 pg/ml, and the mean value of the index was 4.26±0.94 х 10 9/l, which exceeds the values groups with undetectable PD-L1, but the differences were not statistically significant.The obtained result may indicate the influence of the immunosuppressive properties of the tumor on the state of the patient's immunity. Comprehensive determination of tumor PD-L1 expression, serum interleukin 1 beta concentration and the ratio of neutrophils and lymphocytes in peripheral blood can be used as an assessment of the patient's immune status before starting treatment with checkpoint inhibitors.

Las queratosis actínicas son lesiones cutáneas preneoplásicas frecuentes causadas por una exposición crónica a las radiaciones solares. La obtención de modelos animales que contribuyan a comprender los mecanismos implicados en esta patología y a evaluar nuevas terapias farmacológicas resulta de gran interés para la comunidad científica. Se desarrolló un biomodelo de queratosis actínica en ratones Balb/c, empleando como inductor la radiación UVA. Se aplicaron dos esquemas de irradiación: Grupo I, expuesto a tres sesiones diarias de radiación de 2 h y Grupo II, dos sesiones diarias de 4 h, con igual tiempo de receso entre sesiones y durante un período de 14 días. Se evaluaron parámetros macroscópicos y microscópicos, y la frecuencia de aparición de micronúcleos en sangre periférica. Los animales correspondientes al Grupo I no mostraron lesiones mascroscópicas y microscópicamente evidenciaron una leve acantosis con ausencia de displasia; mientras que en los animales del Grupo II se observaron lesiones macroscópicas que se correlacionan histopatológicamente con la presencia de una queratosis actínica. La frecuencia de micronúcleos obtenida en el Grupo II fue significativamente superior a la formación de micronúcleos espontáneos en el Grupo Control. El biomodelo experimental de queratosis actínica obtenido reproduce el efecto de las radiaciones ultravioletas sobre la piel. Actinic keratoses are frequent preneoplastic skin lesions caused by chronic exposure to solar radiation. Obtaining animal models that contribute to understanding the mechanisms involved in this pathology and evaluating new pharmacological therapies is of great interest to the scientific community. A biomodel of actinic keratosis was developed in Balb/c mice, using UVA radiation as an inducer. Two irradiation schemes were applied: Group I, exposed to three daily radiation sessions of 2 h and Group II, two daily sessions of 4 h, with the same break time between sessions and for a period of 14 days. Macroscopic and microscopic parameters were evaluated, as well as the frequency of appearance of micronuclei in peripheral blood. The animals corresponding to Group I did not show mascroscopic lesions and microscopically they showed a slight acanthosis with the absence of dysplasia; while in Group II animals macroscopic lesions were observed that histopathologically correlate with the presence of an actinic keratosis. The frequency of micronuclei obtained in Group II was significantly higher than the formation of spontaneous micronuclei in the Control Group. The experimental biomodel of actinic keratosis obtained reproduces the effect of ultraviolet radiation on the skin. Ciencias Experimentales

Paired-like homeobox 2B (PHOX2B) is a highly sensitive and specific biomarker for diagnosing neuroblastoma, as well as detecting minimal residual disease in neuroblastoma. The clinical significance...

Recent investigations suggested that deregulated levels of Circular RNAs (circRNAs) could be associated with type 2 diabetes mellitus (T2DM) pathogenesis. Accordingly, this study aimed to determine the expression levels of circulating CircHIPK3, CDR1as and their correlation with biochemical parameters in patients with T2DM, pre-diabetes and control subjects. The expression of circRNAs in peripheral blood was determined using QRT-PCR in 70 patients with T2DM, 60 pre-diabetes and in 69 age and sex matched healthy controls. Moreover, bioinformatics tools were applied to explore and predict the potential interactions between circRNAs and other non-coding RNAs (ncRNAs). Our analysis revealed that the expression level of CircHIPK3 was significantly elevated in T2DM patients compared to healthy participants (P

Background The amounts of circulating cell-free DNA (cfDNA) and circulating-tumor DNA (ctDNA) present in peripheral blood liquid biopsies can vary due to preanalytic/analytic variables. In this study, we examined the impact of patient age, sex, stage, and tumor type on cfDNA yield, ctDNA fraction, and estimated ctDNA quantity from a large cohort of clinical liquid biopsy samples. Methods We performed a retrospective analysis of 12 139 consecutive samples received for liquid biopsy (FoundationOne® Liquid) clinical testing. Results Significant differences in both cfDNA yield and estimated ctDNA quantity were observed based on the underlying tumor type that initiated the liquid biopsy analysis and the stage of the patient (P Conclusions In this study, we show that ctDNA quantity varied significantly based on patient age, sex, stage, and tumor type, which could offer an explanation as to why certain liquid biopsy specimens are more likely to fail sequencing or provide clinically meaningful results. In addition, this could affect future clinical decisions on the blood sample volumes required to allow successful liquid biopsy testing.

Key Points Candidate discovery of translational feasibility for noninvasive measurement of miRNA from plasma vesicles as a biomarker for AML patients.Preclinical validation of miR-1246 (candidate among 15 miRNA) as a potential minimally invasive AML biomarker for early monitoring of MRD., Recurrent disease remains the principal cause for treatment failure in acute myeloid leukemia (AML) across age groups. Reliable biomarkers of AML relapse risk and disease burden have been problematic, as symptoms appear late and current monitoring relies on invasive and cost-ineffective serial bone marrow (BM) surveillance. In this report, we discover a set of unique microRNA (miRNA) that circulates in AML-derived vesicles in the peripheral blood ahead of the general dissemination of leukemic blasts and symptomatic BM failure. Next-generation sequencing of extracellular vesicle-contained small RNA in 12 AML patients and 12 controls allowed us to identify a panel of differentially incorporated miRNA. Proof-of-concept studies using a murine model and patient-derived xenografts demonstrate the feasibility of developing miR-1246, as a potential minimally invasive AML biomarker.

Preservation of the brain is important to reducing recurrent seizures and other neurological sequelae after status epilepticus (SE). Medical ozone (MedO3) shows antioxidant, anti-inflammatory and anti-apoptotic properties in the human body. In this study, it was aimed to understand the neuroprotective potential of MedO3 in the acute period after SE. Mature rats of Wistar Albino were used for the study. Group design O3 + SE: SE induced after MedO3, O3: MedO3 alone was given, SE: SE only induced, SE + O3; MedO3 given after SE, C: control and S: sham control group. SE was induced with lithium-pilocarpine experimental model and evaluated on the Racine scale. Peripheral blood samples and brain tissue samples were taken before decapitation. Histopathological evaluation of the hippocampus of the rats given medical O3 before and after SE were studied. The highest peripheral blood oxidative stress index (OSI) was found in SE group. The OSI level in O3 + SE and SE + O3 was significantly higher than SE/C/S. Gene expressions of TNF-α and IL-1β mRNA were significantly higher in SE compared to other groups. Histopathologically; eosinophilia, cellular shrinkage and interstitial oedema were detected in the most severe SE and to a lesser extent in O3 + SE/ SE + O3. MedO3 reduced SE-induced oxidative damage, neuroinflammation and neuronal injury and contributed positively to neuroprotection.

Objective: To investigate the factors related to the prognosis of Neuromyelitis Optica Spectrum Disorder (NMOSD) in cerebrospinal fluid and peripheral blood examination. Methods: In this study, we enrolled 111 patients who were admitted to the First Affiliated Hospital of Zhengzhou University between January 2016 and January 2018 and diagnosed with NMOSD. The patients were divided into the relapse group (n = 48) and remission group (n = 67). Before treatment, all the patients underwent a routine Cerebrospinal Fluid (CSF) and peripheral blood test on the second morning of admission. The association between laboratory data and disease prognosis was evaluated. Results: The immunoglobulin G (IgG) level in the serum showed a strong correlation with the relapse of patients, especially in the aquaporin-4-Antibody (AQP4-Ab) positive group (p2 = 0.053, p=0.015). Conclusion: The serum IgG level and NLR of first-attack patients were correlated with the prognosis of NMOSD.

Allogeneic stem cell transplantation (SCT) offers a potential cure for some hematological malignancies. For those patients without a family donor, unrelated donor (MUD) registries serve for identifying the best donor. In the present study, we aimed to give a cross-sectional report of our registry's activity and experience as the first established national MUD registry in the country. The study is retrospective and covers the period of 2016 to 2019. A total of 1855 donor searches were performed, and 642 were included in the study. All data were electronically obtained from the institutional database system. All SCTs were either 10/10 or 9/10 HLA matched and originated from an international registry. The most preferred stem cell source was peripheral blood (70.2%). A quarter of transplants were performed using bone marrow, and cord blood was used with a rate of 1.4%. The pandemic-related problems were similar for the other two national registries. During the pandemic, 71 of 432 patients who were searched for donors underwent stem cell transplant(SCT). The low number was related mostly with postponing of SCTs and/also difficulties in continuing of volunteering and in achievement of stem cells from international registry. During the Covid19 pandemic, the SCT activity of centers decreased according to the national, and international guidelines. The study revealed an organized, and multidirectional capacity of the registry and also the adaptation to unpredicted conditions such as pandemic. On the other hand, there is a need for more effective strategies for donor recruitment and retention programme.

Objective: To evaluate the performance of Nucleated RBC (NRBC) Count using a fully automated haematology analyzer versus manual counting. Study Design: Cross-Sectional Study. Place and Duration of Study: Department of Hematology, Armed Forces Institute of Pathology, from Sep 2019-Jun 2020. Methodology: Routine fresh whole blood samples were run on Sysmex XN-3000 automated haematology analyzer and 384 samples with results of ≥0.1% Nucleated red blood cells were included in this study. Manual NRBC counting was carried out twice on Leishman-stained peripheral blood smears from all 384 samples. Comparison between manual and automated nucleated red blood cell counting methods was statistically analyzed through linear regression analysis & coefficient correlation. The degree of agreement between two methods was analyzed through Bland-Altman plot. Finally, concordance between the two methods was also analyzed at 5 different ranges of nucleated red blood cells. Results: Linear regression analysis revealed a (r2) value of 0.97. Regression equation was calculated as XN = 0.76MC ± 1.28, with 95% limits of agreement between ± 40.42% and -24.47%. A mean bias of 7.97% was demonstrated through Bland-Altman plot. Concordance analysis revealed a concordance rate of 93.74% (360/384). Nucleated red blood cell counting between two methods were more concordant when nucleated red blood cell counts were

Introduction Immune cells and molecules are considered as clinical biomarkers and potential targets for immunotherapy. Analyses of the composition of peripheral blood cells hold promise for providing a basis for diagnosing and prognosis lung cancer. In this study, we assessed correlations between immune cell subset profiles in peripheral blood and disease prognosis in patients with lung cancer. Methods One hundred and thirteen patients with lung cancer and 99 age‐matched healthy people were enrolled in this study. The percentage and cell count of monocytes, neutrophils, T cells, B cells, natural killer (NK), and NKT cells in peripheral blood were analyzed by flow cytometry or peripheral blood analyzer. Serum cytokines and colony‐stimulating factors were detected by enzyme‐linked immunosorbent assay (ELISA). Results A reduction in antitumor NK cells (p, One hundred and thirteen patients with lung cancer and 99 age‐matched healthy people were enrolled for analysis of immune cell profiles, cytokines, and colony‐stimulating factors in peripheral blood. Monocyte and neutrophil counts were higher in lung cancer patients with histories of smoking, drinking, and liver metastasis. Serum levels of granulocyte colony‐stimulating factor (G‐CSF) and granulocyte‐macrophage colony‐stimulating factor were higher in lung cancer patients, and G‐CSF levels positively correlated with disease severity.

Management of testicular germ cell tumor (GCT) patients is based on clinical determinants, mainly CT scan and serum tumor markers (alpha-fetoprotein, beta subunit of HCG and LDH). Treatment decisions are usually straightforward for patients with clear evidence of metastatic disease, confirmed either by imaging tests or by unequivocal elevated tumor markers. However, there are several clinical scenarios where the assessment of metastatic disease is complicated by the limited specificity of the current imaging tests and serum tumor markers. These include patients with clinical stage IIA GCT with negative tumor markers and patients with post-chemotherapy residual disease where, in absence of clear indicators of GCT, decision making and patient treatment allocation become challenging. Therefore, more accurate biomarkers are critical to reduce the risk of under-or over-treatment and to always deliver the most optimal therapy. The objectives of this narrative review are to review the available publications about micro-RNAs in GCT s and their potential clinical applications. Two clusters of micro-RNAs, miR-371a-3p and miR-302/367, specifically expressed by both seminoma and non-seminoma GCT and easily detectable in the peripheral blood, have demonstrated to be promising in this endeavor. Large prospective trials are ongoing to define the operating characteristics of these biomarkers and their clinical utility to improve GCT patient management and reduce the error rate deriving from clinical uncertainty, therefore reducing the risk of sub-optimal treatments.

Abnormal thyroid hormone (TH) function has been observed in all components of metabolic syndrome (MetS), but the mechanisms remain unclear. Altered genomic methylation status is closely related to MetS. Our aim was to determine whether methylation regulation in TH function–related genes is involved in MetS. In a small strictly selected cohort, low TH function was observed in MetS group, as well as lower THRB promoter methylation levels in peripheral blood leukocytes in a genome-wide methylation screening by Illumina 450K beadchip. The results of beadchip assay were then confirmed by Sequenom MassARRAY. Low THRB promoter methylation levels and low TH function in MetS were confirmed in another big-size validation cohort. Lower methylation levels were associated with higher THRB expression in peripheral blood leukocytes, and altered THRB promoter methylation status influenced its promoter activity and expression. In the MetS rat models constructed by high fat and high fructose diet, lower TH function was also observed, as well as lower Thrb promoter methylation levels. Furthermore, systematic inflammation observed in MetS was found to induce decreased THRB promoter methylation levels as well as corresponding THRB expression. Additionally, oral treatment with a physiological T3 dose mitigated hypertension and insulin resistance and partially alleviated hepatic steatosis and adipocyte hypertrophy in MetS rats. Low methylation levels of THRB promoter in peripheral blood leukocytes induced by systematic inflammation were involved in low TH function in MetS, whereas low TH function deteriorates MetS. This might serve as a novel therapeutic target of MetS.

Introduction This study is to investigate the effect of late-onset hemorrhagic cystitis (LOHC) on progression-free survival (PFS) of patients after haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). Methods This retrospective study enrolled 74 patients with hematological malignancies treated with a myeloablative conditioning regimen and haplo-PBSCT. The effect of LOHC on PFS was studied in terms of HC occurrence, grade, disease type, duration, onset time, gender, and age. Results There were 28 patients with LOHC, and no case was with early-onset HC. The cumulative incidence of LOHC was 37.8% (95% CI: 26.9–48.7%). The 2-year expected PFS of 74 patients and 34 AML patients was not significantly different between LOHC patients and patients without HC (P > 0.05). Among 27 ALL patients, the 2-year expected PFS of LOHC patients was 75%, significantly higher than patients without HC (54.2%) (P < 0.05). The 2-year expected PFSs of patients with mild LOHC and severe LOHC were 69.8 and 77.8%, respectively (P > 0.05). Similarly, the onset time, duration, age, and gender of LOHC patients did not show significant effects on PFS (P > 0.05). Conclusions After haplo-PBSCT, LOHC has a significant effect on the PFS of ALL patients. The HC grade, duration, onset time, gender, and age have no significant effect on PFS.

PurposeEosinopenia has been described in COVID-19. With this study, we aim to study the peripheral blood eosinophil counts in COVID-19 patients and to investigate whether there is an association between the peripheral blood eosinophil counts and disease severity of COVID-19.MethodsWe revised the electronical medical records of confirmed COVID-19 patients with polymerase chain reaction (PCR) assays in the Groene Hart Ziekenhuis, Gouda, The Netherlands. We divided patients in mild, moderate and severe groups based on clinical severity of COVID-19. Clinical severity was based on the therapy needed and the outcome of patients. We compared clinical characteristics, laboratory results and outcome between the three groups.ResultsOf the 230 patients included in this study, the mild, moderate and severe groups consisted of 16.5%, 45.7% and 37.8% of the included patients, respectively. The mean age was 68 years (IQR 57–78). 63% of patients were male. A significant decrease in the peripheral eosinophil counts was found corresponding to the increase of COVID-19 severity. In the mild, moderate and severe groups, the percentage of patients with eosinopenia was 73.7%, 86.7% and 94.3%, respectively (pvalue 0.002).ConclusionEosinopenia is significantly more frequent present in patients with a severe COVID-19.

Introduction Coronavirus disease 2019 (COVID‐19) caused by SARS‐CoV2 can present from mild flu‐like symptoms to acute respiratory distress syndrome. There is multi‐organ involvement; particularly, hematopoietic system can be associated with morphological changes in blood cells of COVID‐19 patients. Method We conducted a cross‐sectional study on a cohort of 50 COVID‐19 patients, confirmed on RT‐PCR with documented cycle threshold (Ct) value. Peripheral blood sample of these patients was collected and examined for complete blood counts (CBC) on automated haematological analyser as well as Leishman‐stained blood smears to look for morphological changes in blood cells. Morphological changes were evaluated with reference to clinical severity and Ct value. Additionally, association between Ct value and clinical severity was also performed. Statistical tests were performed, and P value

Objective: This study aims to determine diagnostic accuracy of peripheral blood smear and automated haematology analyzer and to determine frequency of different types of anemia diagnosed by peripheral blood smear and automated hematology analyzer. Study Design: Cross Sectional study. Setting: Department of Pathology, Rawal Institute of Health Sciences, Islamabad. Period: November 2015 to April 2016. Material & Methods: Sample size of 149 suspected anemia patients was calculated using WHO calculator with 95% confidence interval. Research approval was taken from hospital ethical board. Patients were approached through non probability consecutive sampling method. Both peripheral blood smear examination and automated haematology analysis of each sample was performed. Diagnostic accuracy and frequency of anemia types was measured. Data analysis was done with the help of SPSS version 25. Chi-square and fissure exact test and ROC curve analysis was applied and significant (p

The article presents data on the relevance of differential diagnosis of acute respiratory diseases and pneumonia in military personnel. The results of studying the cytomorphological changes in the pool of neutrophils in the servicemen with acute respiratory infections (ARI) and atypical pneumonia (AP) were obtained during Anti-Terrorist Operation/Joint Forces Operation. These results showed the possibility of using cytomorphological changes of peripheral blood neutrophils as additional criteria for the differential diagnosis of AP and ARI in the first days of the disease. Moreover, only changes in the content of neutrophil pools, in particular for AP, can serve as additional diagnostic criteria in the differential diagnosis of AP and ARI, because in contrast to ARI, it is an increase in the relative content of hyposegmented neutrophils to 1/3 of the population or more. The obtained results can be used in the comprehensive development of additional criteria for the differential diagnosis of acute respiratory diseases and atypical pneumonia in the first days of the disease., В статье приведены данные об актуальности дифференциальной диагностики острых респираторных заболеваний (ОРЗ), пневмоний у военнослужащих. Представлены результаты изучения цитоморфологических изменений пула нейтрофилов у военнослужащих с острыми респираторными заболеваниями и атипичной пневмонией (АП) во время проведения АТО/ООС. Полученные результаты показали возможность использования цитоморфологических изменений нейтрофилов периферической крови в качестве дополнительных критериев для дифференциальной диагностики ПА и ОРЗ в первые дни заболевания. При этом, в качестве дополнительных диагностических критериев при дифференциальной диагностике АП и ОРЗ, могут использоваться только показатели содержания измененных клеток в пуле нейтрофилов, в частности для АП, в отличие от ОРЗ, это увеличение относительного содержания гипосегментированных нейтрофилов до 1/3 пула и более. Полученные результаты могут быть использованы в комплексной разработке дополнительных критериев дифференциальной диагностики острых респираторных заболеваний и атипичной пневмонии в первые дни болезни., У статті наведені дані щодо актуальності диференціальної діагностики гострих респіраторних захворювань (ГРЗ), пневмоній у військовослужбовців. Подані результати вивчення цитоморфологічних змін пулу нейтрофілів у військовослужбовців із гострими респіраторними захворюваннями й атиповою пневмонією (АП) під час проведення АТО/ООС. Отримані результати показали можливість використання цитоморфологічних змін нейтрофілів периферичної крові як додаткових критеріїв для диференціальної діагностики АП та ГРЗ у перші дні захворювання. Причому як додаткові діагностичні критерії при диференціальній діагностиці АП і ГРЗ можуть слугувати лише показники вмісту змінених клітин в пулах нейтрофілів, зокрема для АП, оскільки на відміну від ГРЗ це є збільшенням відносного вмісту гіпосегментованих нейтрофілів до 1/3 пулу або більше. Отримані результати можуть бути використані в комплексній розробці додаткових критеріїв диференціальної діагностики гострих респіраторних захворювань та атипової пневмонії в перші дні захворювання.

Kimura’s disease (KD) is currently considered a rare chronic inflammatory disease of unknown etiology. It is more common in the Asian population, especially in young and middle-aged men, and can involve the lymph nodes, salivary glands, and subcutaneous tissues. It has been reported in adults and children, and is often accompanied by elevated peripheral blood eosinophils and elevated serum immunoglobulin E (IgE). Herein, we report a case of KD in a 46-year-old man with bilateral masses behind the ears since childhood that had gradually enlarged over 40 years. The patient’s peripheral blood eosinophils were elevated, and interestingly, homocysteine levels were also elevated. After surgical resection of the bilateral posterior auricular masses, follow-up over 5 years indicated good recovery and no signs of recurrence.

Objectives Prognostically relevant chromosomal abnormalities in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) are routinely identified by fluorescence in situ hybridization (FISH) on peripheral blood or bone marrow specimens. We studied the prevalence of chromosomal abnormalities on extramedullary tissues involved by CLL/SLL and evaluated their association with prominent proliferation centers (PPCs). Methods FISH for recurrent abnormalities in CLL/SLL was performed on formalin-fixed, paraffin-embedded biopsy sections. PPCs were identified on H&E-stained sections. Available FISH results on peripheral blood or bone marrow specimens were also reviewed. Results Recurrent FISH abnormalities were detected in 69% of 320 CLL/SLL biopsy specimens studied, including +12 (35%), 13q– (24%), 11q– (15%), 17p– (6%), 6q– (2%), and IGH/BCL2 (0.9%). Forty-three patients had abnormal blood or bone marrow FISH analyses, of whom 7 (16%) had discordant +12 and/or 13q–, and 3 (7%) had discordant 17p– or 11q–. Morphology was positive (17%), negative (78%), or equivocal (6%) for PPCs on 247 evaluable biopsy specimens, a finding not significantly associated with FISH results (P = .7). Conclusions Trisomy 12 is overrepresented in tumoral CLL/SLL involvement, compared with the known predominance of 13q– in blood. Discrepancies between leukemic and tissue FISH findings are occasionally encountered. FISH results do not correlate with the presence of PPCs.

Introduction Developing prognostic markers can be useful for clinical decision‐making. Peripheral blood (PB) examination is simple and basic that can be performed in any facility. We aimed to investigate whether PB examination can predict prognosis in coronavirus disease (COVID‐19). Methods Complete blood count (CBC) and PB cell morphology were examined in 38 healthy controls (HCs) and 40 patients with COVID‐19. Patients with COVID‐19, including 26 mild and 14 severe cases, were hospitalized in Juntendo University Hospital (Tokyo, Japan) between April 1 and August 6, 2020. PB examinations were performed using Sysmex XN‐3000 automated hematology analyzer and Sysmex DI‐60 employing the convolutional neural network‐based automatic image‐recognition system. Results Compared with mild cases, severe cases showed a significantly higher incidence of anemia, lymphopenia, and leukocytosis (P

Non-small cell lung cancer (NSCLC) is a malignant cancer worldwide. Long non-coding RNAs (lncRNAs) have emerged as key players in the development and progression of NSCLC, and may be potential biomarkers of NSCLC. Here, we investigated the clinical significance of lncRNA oxidative stress responsive serine rich 1 antisense RNA 1 (OSER1-AS1) in peripheral blood of patients with NSCLC. OSER1-AS1 in peripheral blood of patients with lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and healthy subjects was detected, and the clinical diagnostic efficacy was analyzed. The correlation between OSER1-AS1 expression and clinicopathological features in patients with LUSC and LUAD was analyzed. The downstream mechanism of OSER1-AS1 was explored. The area under the ROC curve of lncRNA OSER1-AS1 and miR-1298-5p/CHSY3 in LUSC and LUAD was compared using the MedCalc analysis. OSER1-AS1 was low in peripheral blood of patients with LUSC and LUAD. The area under the ROC curve for predicting LUSC was 0.800. The area under the ROC curve for predicting LUAD was 0.728. In LUSC and LUAD, OSER1-AS1 deficiency was associated with tumor node metastasis stage, lymph node metastasis, distal metastasis, and poor prognosis. miR-1298-5p was highly expressed, while chondroitin sulfate synthase 3 (CHSY3) was lowly expressed in patients with LUSC and LUAD. miR-1298-5p had target relations with OSER1-AS1 and CHSY3. lncRNA OSER1-AS1 had a higher diagnostic value in patients with NSCLC than miR-1298-5p and CHSY3. Overall, low expression of OSER1-AS1 in peripheral blood of NSCLC patients has high clinical significance, which provides a certain reference value for NSCLC early diagnosis.

Extra medullary relapse (EMR) is the major concern of treatment failure in acute lymphoblastic leukemia (ALL). Hence, their early detection may improve prognosis. Aim of the study is to identify risk factors and outcome of EMR patients with and without concurrent medullary relapse. We retrospectively analyzed 113 patients of ALL who presented with EMR in a tertiary cancer care hospital. Patients were divided into two groups; Group 1, combined EMR (with medullary relapse) and Group 2, isolated EMR (without medullary relapse). Clinical characteristics including total leukocyte count (TLC) & peripheral blood blast percentage during presentation, phenotype, initial central nervous system (CNS) involvement and BCR-ABL translocation were analyzed to identify risk factors for EMR. Incidence of EMR in our study was 15.7% (113/720 patients). Two year incidence of combined EMR and isolated EMR was 10.1% and 5.5% respectively. CNS, followed by testis was common sites of EMR. TLC >50x109/L and peripheral blood blast percentage >50% at presentation was common in Group 1. BCR-ABL translocation was frequent in Group 2 and in adults compared to children (p=0.027). While Group 1 patients presented with leukocytosis (TLC >10X109/L), Group 2 patients presented with leukopenia (TLC 50X109/L and BCR-ABL translocation were identified as risk factors for combined EMR (p=0.004) and for in adults with isolated EMR (p=0.001) respectively.

Oral cancers are the seventh most common cancer globally. While progresses in oral cancer treatment has been made, not all patients respond to these therapies in the same way. To overcome this difficulty, numerous studies have been devoted to identifying biomarkers, which enable early identification of patients who may benefit from a particular treatment modality or at risk for poor prognosis. Biomarkers are protein molecules, gene expression, DNA variants, or metabolites that are derived from tumors, adjacent normal tissue or bodily fluids, which can be acquired prior to treatment and during follow-up, thus extending their use to the evaluation of cancer progression and prediction of treatment outcome. In this review, we employed a basic significance level (< 0.05) as the minimal requirement for candidate biomarkers. Effect sizes of the biomarkers in terms of odds ratio, hazard ratio and area under the receiver operating characteristic curves were subsequently used to evaluate the potential of their clinical use. We identified the CCND1 from the tumor, human papillomavirus, HSP70, and IL-17 from the peripheral blood, and high density of CD45RO+ tumor-infiltrating lymphocytes as the clinically relevant biomarkers for oral cancers.

Aim. To identify the factors influencing the development of postoperative atrial fibrillation (POAF).Methods. The study included 100 patients with indications for cardiac surgery, aged 53 to 82 years (mean age 67.2±17 years). The group included patients who had no history of AF before surgery. Cardiac surgery in the group was presented in 63 patients by coronary artery bypass grafting, and in 37 – by intervention on the heart valves. All respondents were divided into 2 groups: the first included 39 people (39%) who had AF paroxysms lasting more than 30 seconds in the early postoperative period, with a peak at 1–2 days, in 13 (33.3%) cases of AF relapsed. The second group of patients was represented by 61 patients (61%) without cardiac arrhythmias after surgery.Results. The dependence of the development of POAF on age, the concentration of C-reactive protein in the peripheral blood taken on the day of cardiac surgery, the longitudinal size of the left atrium before surgery was revealed.Conclusion. It was found out that a number of factors such as age, preoperative left atrium size, C-reactive protein level in the first days after surgery suggest the development of POAF. The use of the predictors obtained can make it possible to develop an effective strategy for the prevention of POAF.

The malattia leventinese is an autosomal dominant inherited disease whose symptoms appear between the second and fourth decades of life. It is characterized by the appearance of drusen located between the retinal pigment epithelium and the Bruch membrane. It is usually associated with low vision and may progress to blindness. The pathogenic variant p.Arg345Trp in the EFEMP1 gene has been associated with this disease. We characterized clinically and molecularly a family with malattia leventinese using a comprehensive approach that involved ophthalmologists, pediatricians, and geneticists. This approach is of great importance since the phenotype of this disease is often confused with acular degeneration. All family members underwent ophthalmological evaluation and DNA extraction from a peripheral blood sample. All exons of the EFEMP1 gene were amplified and sequenced. The pathogenic variant p.Arg345Trp was identified in affected individuals in this family. This is the first report of malattia leventinese in a family with the p.Arg345Trp pathogenic variant in Colombia. The molecular diagnosis of retinal dystrophies is essential to differentiate this type of pathology.La malattia leventinese es una enfermedad hereditaria autosómica dominante, cuyos síntomas se inician entre la segunda y la cuarta décadas de la vida. Se caracteriza por la aparición de drusas localizadas entre el epitelio pigmentario de la retina y la membrana de Bruch; suele reducir la visión drásticamente y progresar a ceguera. La variante patogénica p.Arg345Trp en el gen EFEMP1 se ha asociado con esta enfermedad. Se presenta aquí la caracterización clínica y molecular de una familia con malattia leventinese mediante un manejo integral que involucró a oftalmólogos, pediatras y genetistas, lo que es de gran importancia, ya que el fenotipo de esta enfermedad suele confundirse con la degeneración macular. A todos los individuos de la familia se les hizo la evaluación oftalmológica con imágenes diagnósticas de retina y extracción de ADN a partir de una muestra de sangre periférica. Todos los exones del gen EFEMP1 se amplificaron y secuenciaron. La variante patogénica p.Arg345Trp se identificó en los individuos afectados. Este es el primer reporte de malattia leventinese en una familia con la variante patogénica p.Arg345Trp en Colombia. El diagnóstico molecular de las distrofias retinianas es fundamental para diferenciar este tipo de enfermedades.

BACKGROUND Owing to its simplicity, speed, small incision, and low cost, peripheral blood collection is widely used in routine blood testing. However, there are certain differences between the detection results of peripheral and venous blood specimens. This investigation and analysis aimed to investigate and analyze the status and opinions of laboratory physicians on the application of peripheral blood for routine blood testing. METHODS A questionnaire was used to investigate and analyze the current status of laboratory physicians with regards to routine peripheral blood testing. The content of the questionnaire included the following aspects: the proportion of peripheral blood specimens, the difficulty of detecting peripheral blood, factors affecting the results of peripheral blood specimens, the proportion of the simultaneous detection of blood test and C-reactive protein (CRP), as well as the proportion and ideals of hypersensitive CRP (hs-CRP), which included a total of 10 re-examination rules. RESULTS Laboratory physicians from 410 hospitals participated in the investigation. The proportion of routine blood tests using peripheral blood specimens in the laboratory departments of tertiary hospitals was low (P=0.006). Difficulties in routine blood tests with peripheral blood specimens were dominated by insufficient blood volume (67.8%). The factors affecting the results of routine blood tests with peripheral blood specimens were dominated by the mixing method (86.6%). When abnormal results were determined by routine blood tests using peripheral blood specimens, they were retested most commonly by making slide smears (82.4%) or re-examined using the remaining peripheral blood (66.1%). The same rules for re-examination of peripheral and venous blood were applied in most medical institutions (86.1%). When the platelet count decreased in routine blood tests using peripheral blood samples, the most common measures included sample agglutination checks (88.5%), instrument alarm message checks (82.4%), and making slide smears for re-examination (73.6%). More laboratory physicians expected blood analyzers to be integrated instruments that could provide both routine blood and hs-CRP testing (80.5%). CONCLUSIONS There are numerous difficulties in routine blood testing using peripheral blood, and thus, more convenient and accurate blood analysis instruments should be developed.

Objectives This study was to investigate the polymorphism and distribution of alleles of HLA‐B*27 in patients with ankylosing spondylitis (AS) in Han population of southeastern China. Methods A total of 89 peripheral blood samples from southeastern Chinese Han patients with AS that diagnosed according to Modified New York criteria were subtyped using the high‐resolution PCR‐SSP.Exon 2‐3 of HLA‐B*27 gene was amplified and sequenced to further confirm the HLA‐B*27 subtype. Results The frequency of HLA‐B*27 was 99.87% in AS patients. Three subtypes, HLA‐B*2704, HLA‐B*2705, and HLA‐B*2706 were identified. The frequencies for these three alleles were HLA‐B*2704 in 84/88 (95.46%), HLA‐B*2705 in 3/88(3.41%), and HLA‐B*2706 in 1/88 (1.13%) of the HLA‐B*27 positive patients, respectively. Conclusions Our study shows that HLA‐B*2704 has an overwhelming frequency in southeastern Chinese Han AS patients. A combined analysis including previous studies of HLA‐B*27‐subtype distributions in Chinese Han populations showed that HLA‐B*2704 may originate from the southern Han and then migrate and spread to the northern areas, and HLA‐B*2705 show the opposite result.

The article analyses the results of changes in pulse rate, central aortic and peripheral blood pressure recorded at 79 northern higher educational institution teachers (31 men and 48 women) who underwent laboratory-confirmed coronavirus infection (COVID-19 +) during their teleworking period and at 116 teachers (55 men and 61 women) without a coronavirus infection history or with negative laboratory-confirmed results for the presence of M and G antibodies to SARS-CoV-2 (COVID-19˗). A comparative analysis of the studied parameters in the Post-COVID-19 period has been carried out with the focus on age and sex differences. The median (Me) age of teachers who have had COVID-19 is 53 years old for men, and for women it is 47 years old;the data of those who have not had the disease are 35 and 38 respectively. The statistical data among male teachers who have undergone COVID-19 are the following: 29.0% were young, 58.1% were middle-aged, and 12.9% were elderly people;the records among female teachers are 43.8%, 35.4%, and 13.1%. respectively. It was stated that changes after COVID-19 in Central Aortic Systolic Pressure (CASP), Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) as well as in heart rate depended on the patients’ age and the presence of hypertension in them. Among the teachers who underwent COVID-19, 32.9% were with hypertension. It was revealed that after COVID-19, the teachers who had not had hypertension before the diagnosis of COVID-19 was made, had some decrease in their heart rate, CASP and SBP;in teachers with hypertension diagnosed prior to COVID-19 with Post-COVID-19 syndrome, an increase in their cSBP, SBP and heart rate was revealed. A statistical analysis with the use of “Statistica” 13.3 program was carried out. To identify differences in quantitative indicators (Me [Q25, Q75]) the Mann-Whitney criterion (U) was used, to identify differences in qualitative indicators the χ2 test was used. © 2021, Science and Innovation Center Publishing House. All rights reserved.

The neutrophil-to-lymphocyte ratio (NLR), red blood cell distribution width (RDW), platelet count (PLT), and mean platelet volume (MPV)/platelet ratio (MPR) are commonly known inflammatory markers measured by a routine peripheral blood test that have been studied in patients with febrile seizures (FS) and may be useful for the classification of FS types. The aim of this study was to investigate the relationship between FS and inflammatory markers including MPR, RDW, and NLR and also to determine the diagnostic ability of these parameters to identify FS by comparing patients with and without FS, and by comparing patients with FS to their FS types (simple febrile seizure or complex febrile seizure [SFS or CFS]). The study included a total of 537 children aged 6 to 60 months who presented to the emergency service with FS. The FS group was divided into two subgroups based on the type of seizure, SFS, and CFS. MPR, NLR, and RDW predicted a 1.7 (odds ratio [OR], 95% confidence interval [CI]: 1.19–2.45), 1.94 (OR, 95% CI: 1.35–2.79), and 1.8 (OR, 95% CI: 1.25–2.59) times higher risk of FS, respectively. NLR and RDW predicted a 2.64 (OR, 95% CI: 1.17–4.85) and 2.34 (OR, 95% CI: 1.14–4.44) times higher risk of recurrent SFS, respectively. In patients with CFS, NLR ≥ 1.806 had a 3.64 times (OR, 95% CI: 1.83–7.21) and RDW ≥14.55 had a 3.34 times (OR, 95% CI: 1.67–6.65) higher risk of recurrent FS. The results indicated that MPV, NLR, and RDW differentiated not only SFS from CFS but also FS from fever without seizure. The increase in RDW and NLR values and their diagnostic values in patients with recurrent FS and the diagnostic value of these parameters in predicting CFS suggest that NLR and RDW could be effective, practical, and discriminative predictors of FS.

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524–9.048), 1.261 (IQR, 0.817–2.000), and 1.00 (IQR, 0.726–1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U = 234.0; P

BACKGROUND In the evaluation of patients with non-Hodgkin lymphoma (NHL), determination of bone marrow involvement is an integral part of staging work up. Peripheral blood counts and examination of blood smears are also done in patients with lymphoma as part of pre-treatment investigations. METHODS A cross sectional study of 78 patients with a prior histopathological diagnosis of NHL was conducted. Peripheral blood counts were performed on an automated haematology analyser to look for various cytopenias. Peripheral blood smears and bone marrow aspirate (BMA) / imprint smears were examined in detail for atypical lymphoid cells. Bone marrow trephine biopsies of these patients were studied to assess the NHL involvement and the various patterns of involvement. Adjuvant immunohistochemistry (IHC) was performed in bone marrow biopsies with scant cellularity or crush artefact to discern the marrow involvement. RESULTS Bone marrow trephine biopsy showed involvement by lymphoma in 65.4 % cases. The incidence of involvement was higher in B-cell lymphomas, especially in low grade types. The predominant pattern of involvement was interstitial pattern (41.2 %). Discordant histology between bone marrow and the primary anatomic site was found in 7.8 % of the cases, which was seen more in diffuse large B-cell lymphomas. Majority of the patients with bone marrow infiltration by NHL had anaemia (84.3 %). Bicytopenia and pancytopenia were also observed. On peripheral blood smear examination atypical lymphoid cells were present in 23 % cases. CONCLUSIONS Bone marrow examination is an important aspect in the diagnosis of NHL, because of its both prognostic and therapeutic implications. Hence, the presence of atypical lymphoid cells and other changes in the peripheral blood should be detected in these patients. KEYWORDS Non-Hodgkin Lymphoma, Bone Marrow Biopsy, Bone Marrow Aspirate / Imprint, Peripheral Blood Smear, Atypical Lymphoid Cells

Background The prevention and prognosis of the onset or recurrence of acute myocardial infarction (AMI) is a difficult problem in contemporary research. Methods In this study, peripheral blood samples were collected from seven patients with AMI and nine healthy adults, and exosome microRNAs (miRNAs) were extracted. The miRNA differential expression profiles of serum exosomes in patients with AMI were obtained by using the next-generation sequencing technology combined with bioinformatics analysis. Reverse-transcriptase polymerase chain reaction (RT-PCR) was used to verify the primary screening of differential exosome miRNAs to reveal the possible mechanism of their action on AMI. Results Compared with healthy individuals, 544 miRNAs were upregulated and 518 miRNAs were downregulated in AMI patients preoperatively. Among these miRNAs, we selected miR-6718 and miR-4329 for qPCR verification. The expression of miR6718 and miR-4329 in patients with myocardial infarction was significantly lower than that in normal controls.

Purpose Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic lung disease of unknown cause with a variable course. Acute exacerbations of IPF (AE-IPF) is sudden accelerations of the disease or a superimposed idiopathic acute injury significantly reducing lung function. To examine the serum concentrations of Progranulin (PGRN) and activin A in patients with AE-IPF in a pilot study. Methods Twenty-one patients with AE-IPF were compared with 23 patients with stable IPF as a control group. Serum PGRN and activin A levels, arterial blood gas measurements, and lung function were determined in these two groups. Results Peripheral blood PGRN and activin A levels in patients with AE-IPF were 83.7 + 10.0 and 14.2 ± 1.7 ng/ml (mean + SD), respectively; higher than those in the control group 61.0 + 5.8 and 5.8 + 1.0 (p r = − 0.857 (p r = − 0.757 (p Conclusion Progranulin (PGRN) and activin A may be involved in the pathogenesis of AE-IPF. They may be possible markers of disease activity in AE-IPF.