Immature Granulocytes Research Articles

Neutrophil Reactivity Intensity and misclassification of immature granulocytes.

Immature granulocyte percentage (IG%) is an important biomarker for infection control. We observed spurious cases where the IG% was dramatically underestimated on the automated Sysmex XN-series hehmatology analyzer compared with manual differential. These cases were associated with high values of "Neutrophil Reactivity Intensity" (NEUT-RI), which should reflect the metabolic activity of the neutrophils. We conducted a three-stage study to evaluate whether NEUT-RI could be utilized to screen for misclassified IG% results defined as the manual differential estimating a 10 percentage points higher IG% compared with the automated Sysmex differential. First, 124 patient samples were selected for 800-cell manual smear analysis based on their NEUT-RI values and compared with the automatic Sysmex IG% results. Next, 11 098 routine 110-cell manual smear analyses were compared with the corresponding Sysmex IG% results. Finally, during a 19-day period 160 additional patient samples underwent smear based on NEUT-RI values ≥56 fluorescence intensity (FI) to screen for misclassified results beyond our current smear practice. NEUT-RI ≥56 predicted IG% misclassification with 91% sensitivity and 88% specificity, but primarily when the internal Sysmex flag "Abnormal WBC Scattergram" was present. 90.1% of misclassified results were identified by this flag. Beyond our existing smear rules including this flag, NEUT-RI ≥56 FI had a positive predictive value below 1%. Both NEUT-RI and the internal Sysmex flag "Abnormal WBC Scattergram" work well to identify cases of IG% misclassification. However, in our setting NEUT-RI ≥56 FI had no meaningful additional predictive capacity to identify misclassifications beyond our current smear rules.

Risk factors for the in‑hospital and 1‑year mortality of elderly patients hospitalized due to COVID‑19‑related pneumonia.

Coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and a high mortality rate, particularly among elderly patients. Since the beginning of the pandemic, an older age has been recognized as a critical risk factor for disease severity, with increasing mortality rates in each decade of life. This phenomenon may be a consequence of a poor previous health status, with a higher prevalence of pre-existing comorbidities and a higher degree of frailty. The majority of studies on the outcomes and risk factors of elderly patients refer to the first waves of the pandemic and the predictors of in-hospital mortality in these patients. The aim of the present study was to provide a detailed description of the clinical characteristics and management of a cohort of elderly patients (≥65 years of age) who were hospitalized with COVID-19-related pneumonia in all phases of the pandemic, presenting their outcomes, and investigating predictors of in-hospital and out-of-hospital mortality over a period of 1 year in this particularly vulnerable population. A total of 1,124 elderly patients (603 males, 53.7%) with a mean age of 78.51±7.42 years and a median Charlson comorbidity index (CCI) of 5 were included in the study. Of these patients, 104 (9.3%) were hospitalized during the period of prevalence of the original strain Wuhan, 385 (34.3%) were hospitalized during the period of prevalence of the Alpha variant, 221 (19.7%) were hospitalized during the period of prevalence of the Delta variant, and 414 (36.8%) were hospitalized during the period of prevalence of the Omicron variant. Overall, the in-hospital mortality rate was 33.4% (375 patients), and the 1-year mortality rate was 44.7% (502 patients). The majority of patients had not been vaccinated or had not completed full vaccination against severe acute respiratory syndrome coronavirus-2 (843 patients, 75%), given the period of infection. Age, immature granulocytes, lactate dehydrogenase (LDH) levels, ferritin levels, chest X-ray score, as well as the absence of full vaccination, cough and fatigue, were statistically significantly and independently associated with in-hospital mortality, while age, LDH levels, ferritin levels, alanine aminotransferase levels, CCI, chest X-ray score, the absence of cough and fatigue, and a history of dementia were statistically significantly and independently associated with 1-year mortality. On the whole, the present study demonstrates that both the in-hospital mortality and 1-year mortality rates of elderly patients hospitalized due to COVID-19-related pneumonia are high.

THE THERAPEUTIC EFFICACY OF PLASMAPHERESIS FOR SEPSIS WITH MULTIPLE ORGAN FAILURE: A PROPENSITY SCORE-MATCHED ANALYSIS BASED ON THE MIMIC-IV DATABASE.

Background: Despite advancements in sepsis treatment, mortality remains high. Plasmapheresis (PE) targeting multiple pathways simultaneously seems to be a potential treatment option, but evidence is insufficient. We aimed to investigate the efficacy of PE for sepsis with multiple organ failure (MOF). Method: Septic patients with MOF were identified from the Medical Information Mart for Intensive Care IV database. Patients who received PE were matched with those receiving conventional therapy via propensity score matching. Regression analyses evaluated the association between PE and outcomes. The Kaplan-Meier (KM) method was used to analyze the survival probability. The generalized additive mixed model investigated early indexes changes' association with treatment modalities and 28-day mortality. Results: Nine hundred six septic patients with MOF were enrolled. After propensity score matching, PE and conventional groups consisted of 60 cases each. Plasmapheresis was associated with a reduced risk of 28-day mortality (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.27-0.94), 1-year mortality (HR, 0.44; 95% CI, 0.26-0.74), and in-hospital mortality (HR, 0.38; 95% CI, 0.20-0.71). The KM curves demonstrated significant differences in survival probability between groups. Compared with the conventional group, the sequential organ failure assessment, norepinephrine dosage, prothrombin time, actate dehydrogenase, total bilirubin, white blood cells, and immature granulocytes in the PE group significantly decreased over time, while platelets, red blood cells, and hemoglobin significantly increased over time. Conclusions: Plasmapheresis demonstrated an association with reduced risks of 28-day, in-hospital and 1-year mortality in septic patients with MOF. Moreover, plasmapheresis might exhibit the potential to improve outcomes by improving organ function, hemodynamics, and restoring several indicators, such as coagulation, anemia, and inflammation.

Applying decision tree algorithms to early differential diagnosis between different clinical forms of acute Lyme borreliosis and tick-borne encephalitis

Background: Tick-borne encephalitis and Lyme borreliosis are the most common natural focal infections in Russia often arising as a mixed infection, which is often clinically difficult to distinguish from a monoinfection at the onset of the disease that is a result of delayed laboratory verification of the diagnosis and it requires further searching for fundamentally new approaches to the issue of early differential diagnosis of tick-borne infections.Aims: is to develop decision tree algorithms for early differential diagnosis between the mono- and mixed forms of acute Lyme borreliosis and tick-borne encephalitis with prevailing febrile syndrome in clinical picture based on clinical and laboratory data.Materials and methods: We retrospectively analyzed 55 clinical and laboratory parameters obtained from 291 hospitalized tick-borne infections patients with or without erythema migrans at the site of ixodid tick bites in the first week of the disease, who were included in the single-center study from 2010 to 2023. In 211 patients without erythema, the analysis was carried out between three classes depending on the diagnosis: the mixed infection of non-erythematous Lyme borreliosis and tick-borne encephalitis, the mono-infection of non-erythematous Lyme borreliosis or the monoinfection of tick-borne encephalitis. The other two classes, which included 80 patients with erythema, had the mixed infection of acute erythematous Lyme borreliosis and tick-borne encephalitis or erythematous Lyme borreliosis monoinfection. Python programming language was applied to develop two decision tree models. Feature importance was assessed for all predictors. Each patient class was randomly divided into training (70%) and testing (30%) datasets. Accuracy evaluation of the models was based on ROC analysis.Results: The decision tree algorithm for early differential diagnosis among the tick-borne infection patients without erythema migrans included the following most important predictors: maximal fever rise, chills, neutrophil-to-monocyte ratio, ESR, absolute number of reactive lymphocytes and immature granulocytes, and percentage of eosinophils. The model for differential diagnosis between the patients with erythema migrans included the following predictors: maximal fever rise, the absolute number of reactive lymphocytes and immature granulocytes, and the percentage of basophils. Both decision tree models showed excellent predictive values based on sensitivity, specificity, precision, accuracy, and F1 scores, as well as areas under the ROC curve, which were higher than 0.90.Conclusions: Based on clinical and laboratory parameters, two decision tree models with high sensitivity have been developed, which can be easily applied in clinical practice for early differential diagnosis of the tick-borne infections with prevailing fever syndrome.

Single Cell Analyses Indicate SRSF2 and TET2 Co-Mutation Results in Skewed Haematopoiesis in Myelodysplastic Syndromes

We used single-cell ATAC-seq (scATAC-seq) to study how synchronous SRSF2 and TET2 co-mutations result in skewed myelopoiesis compared with SRSF2 mutation only in subjects with myelodysplastic neoplasms (MDNs). We identified 621 differentially expressed genes in comparing of transcriptome sequencing data of bone marrow mononuclear cells ( p < 0.01; |log2FC| > 2; Figure 1 A). Up-regulated genes in the co-mutation cohort involved those expressed in pluripotent haematopoietic stem cells (HSCs), cytokine receptor interactions and cancer-related signaling pathways ( Figure 1 B). We extended our observation by interrogating data from the GSE58831 public dataset where we identified 18 similar pathways in subjects with SRSF2 and TET2 co-mutations ( Figure 1 C ). We then used scATAC-seq to verify regulatory networks with genes and transcription factors. 49,532 cells had high-quality scATAC-seq profiles and passed stringent quality filtering with a median of 12,858 fragments per cell 39% of which mapped to peaks. 16 cell types were annotated according to cell marker genes and aligned with the public single cell RNA-seq gene expression matrix of haematopoietic cell types ( Figure 1 D-E). Next, we compared transcription factor (TF) and cis-elements active during differentiation of HSC to myelopoiesis betweenthe SRSF2 and TET2 co-mutation and SRSF2 mutation-only cohorts. In the SRSF2 and TET2 co-mutation cohort we found GATA4, RUNX1, SNAI1, REL and JDP2 favour myeloid differentiation and in NF-KB related inflammatory responses. Related gene activity correlated with high activity of inflammatory cytokines such as BCL2A1, EGR1, IL-1β, and NLRP3( Figure 1 F). SRSF2 and TET2 co-mutations result in early clonal dominance at the haematopoietic stem cell stage. 19,836 peaks were accessible in SRSF2 and TET2 co-mutated samples and annotated for putative functions by GREAT ontology enrichment analysis ( Figure 1 G-H). More accessibility peaks in SRSF2 and TET2 co-mutation were restricted to cancer-related process (reactive oxygen species biosynthetic process, regulation of phagocytosis, intrinsic apoptotic signaling pathway, mRNA catabolism) and cytokine related pathways (IL-1 mediated signaling pathway) compared with SRSF2 mutation-only samples. Next, we focused on the IL-1-mediated signaling pathway, a regulator of HSC function. We isolated umbilical cord blood HSCs (CD34+) monitored their expansion in liquid culture with or without (IL-1A or IL-1B (25 ng/ml). HSCs cultured with IL-1A or IL-1B differentiated and expanded significantly faster than untreated HSCs over 7-day period ( Figure 1 I). To directly address the effects of IL-1 on HSC differentiation we used colony formation assays in methylcellulose ± IL-1. Strikingly, IL-1-treated HSCs produced almost exclusively myeloid-committed granulocyte/macrophage (GM)-type colonies containing abundant macrophages (CFU-GM), a higher proportion of immature multi-lineage granulocyte/ erythrocyte /macrophage/megakaryocyte (CFU-GEMM)-type colonies containing mostly immature myeloblasts and a lower proportion of burst-forming unit-erythroid (BFU-E). IL-1-treated HSCs also had decreased re-placing capacity ( Figure 1 J-K). Next, we constructed a SRSF2 P95H single mutation and SRSF2 P95H mutation with TET2 knockout cell lines. We found that co-mutant cells had significantly increased NLRP3 and IL-1β expression in LPS (1 ug/ml) and ATP (5 mM) treated cultures whereas no change was detected IL-1α expression ( Figure 1 L-M). In conclusion, our data preliminary indicate SRSF2 and TET2 co-mutated causes increased NLRP3-mediated IL-1β secretion resulting in skewed differentiation of HSCs in persons with MDNs.

Imatinib resistance in CML and its association with age & gender.

Objective: To evaluate the association of gender and age with the resistance shown to Imatinib in CML with evaluation of WBCC in different age groups. Study Design: Cross Sectional Analytical study. Setting: Islamic International Medical College, Riphah International University, Islamabad, Pakistan. Patients were enrolled from the CML clinic in Holy Family Hospital, Rawalpindi. Period: January 2019 to December 2021. Material & Methods: Sampling technique was non probability consecutive sampling. We included 75 newly diagnosed CML patients, who were taking Imatinib 400 mg. Blood samples of all these patients were analysed at the start of treatment and also after 3 months to determine the complete haematological response (CHR) and patients were labelled as resistant who failed to achieve complete haematological response at this stage according to the Leukemia Net guidelines. Results: Our study demonstrates that 54.7% of the patients were Imatinib responders while 45.3 % patients were Imatinib resistant. Patients who were labelled as responders have shown complete haematological remission at 3 months of treatment. (Platelet Count < 450 x 10 9/L - WBCC < 10 x 10 9/L - Differential without Immature Granulocytes (MC, PMC, MB) and With Less Than 5% Basophils - Non-Palpable Spleen) A chi square test of independence was performed to examine the relation between gender and response and between age groups and response. The relationship between age groups and response is significant with p value of 0.003. While the relationship when determined between gender and response, it was found to be non-significant with p value of 0.08. It was also found out that WBC count in responders is at lowest in second age group and also highest in second age group in case of resistant patients that is age between 31-40 years. Conclusion: Imatinib resistance is common while treating patients with chronic myeloid leukemia. There is significant association with the different age groups and non-significant association with the gender in terms of response to the treatment of Imatinib. It was also found that age also effects the WBC count with Imatinib though it was not significant.

A comparative evaluation of three consecutive artificial intelligence algorithms released by Techcyte for identification of blasts and white blood cells in abnormal peripheral blood films.

Digital pathology artificial intelligence (AI) platforms have the capacity to improve over time through "deep machine learning." We have previously reported on the accuracy of peripheral white blood cell (WBC) differential and blast identification by Techcyte (Techcyte, Inc., Orem, UT, USA), a digital scanner-agnostic web-based system for blood film reporting. The aim of the current study was to compare AI protocols released over time to assess improvement in cell identification. WBC differentials were performed using Techcyte's online AI software on the same 124 digitized abnormal peripheral blood films (including 64 acute and 22 chronic leukaemias) in 2019 (AI1), 2020 (AI2), and 2022 (AI3), with no reassignment by a morphologist at any time point. AI results were correlated to the "gold standard" of manual microscopy, and comparison of Lin's concordance coefficients (LCC) and sensitivity and specificity of blast identification were used to determine the superior AI version. AI correlations (r) with manual microscopy for individual cell types ranged from 0.50-0.90 (AI1), 0.66-0.86 (AI2) and 0.71-0.91 (AI3). AI3 concordance with manual microscopy was significantly improved compared to AI1 for identification of neutrophils (LCC AI3 = 0.86 vs. AI1 = 0.77, p = 0.03), total granulocytes (LCC AI3 = 0.92 vs. AI1 = 0.82, p = 0.0008), immature granulocytes (LCC AI3 = 0.67 vs. AI1 = 0.38, p = 0.0014), and promyelocytes (LCC AI3 = 0.53 vs. AI1 = 0.16, p = 0.0008). Sensitivity for blast identification (n = 65 slides) improved from 97% (AI1), to 98% (AI2), to 100% (AI3), while blast specificity decreased from 24% (AI1), to 14% (AI2) to 12% (AI3). Techcyte AI has shown significant improvement in cell identification over time and maintains high sensitivity for blast identification in malignant films.

Geriatrik Pnömoni Ciddiyeti ve Mortalite Sonuçlarında İmmatür Granülositler ve Çekirdekli Eritrositlerin Prognostik Önemi

Aim: The progression of pneumonia in the senior-age population can be catastrophic. Biomarkers capable of assessing the severity of pneumonia play a pivotal role in prognosis. We conducted an evaluation of the kinetics of immature granulocytes (IG) and nucleated red blood cells (NRBC) as potential indicators of the severity of geriatric pneumonia.
 Materials & Methods: In this retrospective cross-sectional study, patients diagnosed with pneumonia were categorized using two prominent severity scoring systems, CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, age >65) and PSI (Pneumonia severity index). Additionally, the patients' discharge status and infection process markers were noted.
 Results: A total of 80 patients were included in the evaluation, with a mean age of 72.23 ± 7.26. Excluding the mortality rate of 49% when including oncology patients, the overall mortality rate was 26%. The deceased patients had longer hospitalization durations, higher CURB-65 and PSI category classifications, and elevated NRBC results. In CURB-65-based categorization, there was an increase only in NRBC levels associated with disease severity, whereas, in PSI-based categorization, there was an increase in both NRBC and IG levels. No statistical difference was observed in NRBC and IG levels when excluding oncology patients from the analysis.
 Conclusion: In geriatric pneumonia cases, the dynamics of NRBC appear to be more crucial in indicating disease severity compared to IG. However, this opportunity seems to be missed or compromised in patients with oncological comorbidities.

Utility of immature granulocyte count in differentiating between pyelonephritis and cystitis in pediatric patients

Aims: Immature granulocyte (IG) is an easily accessible and inexpensive test that can be measured in hemogram parameters without additional analysis. It can be used in differentiation because of its practical applicability. This study aimed to investigate the role of IG count and inflammation-related complete blood count (CBC) parameters in differentiating between cystitis (CYS) and pyelonephritis (PYL) in pediatric patients.
 Methods: This retrospective cross-sectional study analyzed data from 79 pediatric patients (40 with PYL and 39 with CYS) who presented at a hospital pediatric outpatient clinic between January 2020 - February 2021. In addition to clinical symptoms and signs, laboratory and urinalysis results were evaluated. Laboratory analyses focused on IG count, IG percentage, and all hemogram parameters. 
 Results: No significant demographic differences were observed between the PYL and CYS groups (p>0.05). IG counts, and C-reactive protein levels significantly differed between the two conditions (p

Performance of the new MC-80 automated digital cell morphology analyser in detection of normal and abnormal blood cells: Comparison with the CellaVision DM9600.

Mindray MC-80 is an automated system for digital imaging of white blood cells (WBCs) and their pre-classification. The objective of this work is to analyse its performance comparing it with the CellaVision® DM9600. A total of 445 samples were used, 194 normal and 251 abnormal: acute leukaemia (100), myelodysplastic syndromes/myeloproliferative neoplasms (33), lymphoid neoplasms (50), plasma cell neoplasms (14), infections (49) and thrombocytopenia (5). WBC pre-classification values with the MC-80 and DM9600 were compared with (1) the microscope, (2) Mindray BC-6800Plus differentials in only normal samples, and (3) confirmed or reclassified images (post-classification). Pearson's correlation, Lin's concordance, Passing-Bablok regression, and Bland-Altman plots were used. Sensitivity, specificity, positive (PPV) and negative (NPV) predictive values for abnormal cells using the MC-80 were calculated. The PPV and NPV were above 98% and 99%, for normal samples. For immature granulocytes (IG), NPV and PPV were 100% and 74.2%. When comparing the WBC differentials using the MC-80, the microscope and the BC-6800Plus, no differences were found except for basophils and IG. Our results showed good agreement between the pre- and post-classification of normal WBC, including IG, quantified by high correlation and concordance values (0.91-1). Sensitivity and specificity for blasts were 0.984 and 0.640. The MC-80 detected abnormal lymphocytes in 30% of the smears from patients with lymphoid neoplasm. Plasma cell identification was better using the DM9600. The sensitivity and specificity for erythroblast detection were 1 and 0.890. We found that the MC-80 shows high performance for WBC differentials for both normal samples and patients with haematological diseases.

Can immature granulocyte (IG), an inflammatory marker, be used in the differential diagnosis of epilepsy and non-epileptic psychogenic seizure?

Can immature granulocyte (IG), an inflammatory marker, be used in the differential diagnosis of epilepsy and non-epileptic psychogenic seizure?

Human CD34+-derived complete plasmacytoid and conventional dendritic cell vaccine effectively induces antigen-specific CD8+ T cell and NK cell responses in vitro and in vivo

Allogeneic stem cell transplantation (alloSCT) can be curative for hemato-oncology patients due to effective graft-versus-tumor immunity. However, relapse remains the major cause of treatment failure, emphasizing the need for adjuvant immunotherapies. In this regard, post-transplantation dendritic cell (DC) vaccination is a highly interesting strategy to boost graft-versus-tumor responses. Previously, we developed a clinically applicable protocol for simultaneous large-scale generation of end-stage blood DC subsets from donor-derived CD34+ stem cells, including conventional type 1 and 2 DCs (cDC1s and cDC2s), and plasmacytoid DCs (pDCs). In addition, the total cultured end-product (DC-complete vaccine), also contains non-end-stage-DCs (i.e. non-DCs). In this study, we aimed to dissect the phenotypic identity of these non-DCs and their potential immune modulatory functions on the potency of cDCs and pDCs in stimulating tumor-reactive CD8+ T and NK cell responses, in order to obtain rationale for clinical translation of our DC-complete vaccine. The non-DC compartment was heterogeneous and comprised of myeloid progenitors and (immature) granulocyte- and monocyte-like cells. Importantly, non-DCs potentiated toll-like receptor-induced DC maturation, as reflected by increased expression of co-stimulatory molecules and enhanced cDC-derived IL-12 and pDC-derived IFN-α production. Additionally, antigen-specific CD8+ T cells effectively expanded upon DC-complete vaccination in vitro and in vivo. This effect was strongly augmented by non-DCs in an antigen-independent manner. Moreover, non-DCs did not impair in vitro DC-mediated NK cell activation, degranulation nor cytotoxicity. Notably, in vivo i.p. DC-complete vaccination activated i.v. injected NK cells. Together, these data demonstrate that the non-DC compartment potentiates DC-mediated activation and expansion of antigen-specific CD8+ T cells and do not impair NK cell responses in vitro and in vivo. This underscores the rationale for further clinical translation of our CD34+-derived DC-complete vaccine in hemato-oncology patients post alloSCT.

Risk factors for a differentiation syndrome in patients with acute promyelocytic leukemia

Differentiation syndrome (DS) is a severe complication of acute promyelocytic leukemia and its treatment, which is one of the causes of high early mortality. the similarity of clinical manifestations of DS and other complications that may develop during acute promyelocytic leukemia therapy makes it difficult to diagnose ds. at the same time, untimely initiation of DS therapy with glucocorticosteroids can lead to the patient’s death. The only generally accepted risk factor for ds is initial leukocytosis. Specific markers confirming ds have not yet been found. A number of studies show that in patients with diagnosed DS, the expression of CD56, CD54, CD2, CD15, CD13, markers of immature granulocytes, β2-integrins was more often found on blast cells. exposure to tretinoin increased the expression of chemokine receptors, chemokines, and cytokines by blast cells and vascular endothelium. The influence exerted by atypical promyelocytes, due to their biological characteristics, on the coagulation system suggests an association between hemostasis state and ds development. However, the value of the above markers as predictors or signs of DS still needs to be tested, especially when it comes to non-chemotherapeutic treatment of acute promyelocytic leukemia with arsenic trioxide.

EVALUATION AND DIAGNOSTIC EFFECTIVENESS OF HEMOGRAM, BIOCHEMISTRY AND INFLAMMATORY MARKERS (IMMATURE GRANULOCYTE, PROCALCITONIN, CRP, NLR, PLR) IN PATIENTS WITH SEPSIS

Aim
 This study aimed to reveal the contributions of hemogram values and inflammatory markers involved in the pathology and progression of sepsis, and other biochemical markers such as C-reactive protein, procalcitonin, delta neutrophil index (immature granulocyte), calcium and zinc levels to the diagnosis of sepsis, and the relationship of these markers with each other.
 Material and Method
 This is a descriptive epidemiological study. Patients aged 18 years and over who were diagnosed with sepsis in the Emergency Department and Internal Diseases Service of Kahramanmaraş Sütçü Imam University Medical Faculty Hospital between 11.10.2022 - 11.06.2023 were prospectively included in the study.
 Results
 In our study, it was found that leukocyte, neutrophil, neutrophil lymphocyte ratio, platelet lymphocyte ratio, immature granulocyte, copper, phosphorus, blood glucose, C-reactive protein and procalcitonin values were high in patients with sepsis. The levels of albumin, calcium, zinc and lymphocyte were found to be low. 
 Conclusion
 The use of biomarkers in sepsis has increasingly become important in diagnosing, following treatment, determining prognosis and predicting mortality. The biomarkers examined in this study are believed to be a reference for future studies on their use in the diagnosis, treatment and prognosis follow-up of sepsis.

Developing the POTOMAC Model: A Novel Prediction Model to Study the Impact of Lymphopenia Kinetics on Survival Outcomes in Head and Neck Cancer Via an Ensemble Tree-Based Machine Learning Approach.

Lymphopenia is associated with poor survival outcomes in head and neck squamous cell carcinoma (HNSCC), yet there is no consensus on whether we should limit lymphopenia risks during treatment. To fully elucidate the prognostic role of baseline versus treatment-related lymphopenia, a robust analysis is necessary to investigate the relative importance of various lymphopenia metrics (LMs) in predicting survival outcomes. In this prospective cohort study, 363 patients were eligible for analysis (patients with newly diagnosed, nonmetastatic HNSCC treated with neck radiation with or without chemotherapy in 2015-2019). Data were acquired on 28 covariates: seven baseline, five disease, seven treatment, and nine LMs, including static and time-varying features for absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio, and immature granulocytes (IGs). IGs were included, given their hypothesized role in inhibiting lymphocyte function. Overall, there were 4.0% missing data. Median follow-up was 2.9 years. We developed a model (POTOMAC) to predict survival outcomes using a random survival forest (RSF) procedure. RSF uses an ensemble approach to reduce the risk of overfitting and provides internal validation of the model using data that are not used in model development. The ability to predict survival risk was assessed using the AUC for the predicted risk score. POTOMAC predicted 2-year survival with AUCs at 0.78 for overall survival (primary end point) and 0.73 for progression-free survival (secondary end point). Top modifiable risk factors included radiation dose and max ALC decrease. Top baseline risk factors included age, Charlson Comorbidity Index, Karnofsky Performance Score, and baseline IGs. Top-ranking LMs had superior prognostic performance when compared with human papillomavirus status, chemotherapy type, and dose (up to 2, 8, and 65 times higher in variable importance score). POTOMAC provides important insights into potential approaches to reduce mortality in patients with HNSCC treated by chemoradiation but needs to be validated in future studies.

Early Detection of Blood Culture Positivity in Pediatric Cardiac Surgery Patients Using Immature Granulocyte Percentage and Absolute Count

Early Detection of Blood Culture Positivity in Pediatric Cardiac Surgery Patients Using Immature Granulocyte Percentage and Absolute Count

The Value of Immature Granulocyte and Immature Granulocyte/Total Granulocyte Ratio in Predicting the Need for Surgical Treatment in Patients Diagnosed with Intestinal Ileus in the Emergency Department

Background/Aims: Although many biomarkers that can predict the need for surgical treatment of patients with intestinal ileus have been investigated, effective, inexpensive, and fast-resulting biomarkers have not been determined. In our study, showing the value of immature granulocyte (IG) and immature granulocyte/total granulocyte (IG/TG) ratio in predicting the need for surgical treatment in patients diagnosed with intestinal ileus in the emergency department was aimed. Methods: Our study was carried out as a prospective cohort between 23.11.2021 and 07.04.2022. Patients aged 18 years and older who applied to the emergency department and were diagnosed with intestinal ileus after clinical, laboratory and radiological evaluation were included in the study. Demographic characteristics, comorbidities, treatments, laboratory tests and IG, IG/TG results of the patients were recorded. The patients were divided into two groups as those who underwent surgical treatment and those who did not, and comparisons were made. p value <0.05 was considered statistically significant. Results: A total of 78 patients were included in the study. 46.2% (n=36) of the patients were female and the median age was 65 years. While surgery was performed in 41% (n=32) of the patients, 59% (n=46) were followed up with medical treatment. IG number and IG/TG ratio were found to be higher in patients who underwent surgical intervention than in those who underwent medical treatment, and these differences were statistically significant (p<0.05). In receiver-operating characteristic (ROC) analysis AUC: 0.658 was found for IG number. With the best cut-off value of 0.03, the sensitivity was found to be 56.3% specificity: 71.7%; and the AUC value for IG/TG: 0.627 (95% CI; 0.500-0.753), and when the best cut-off value was taken as 0.2, the sensitivity for this value was 59.4%, and the specificity was 63%. Conclusion: In this study, in which we examined the IG numbers and IG/TG ratios in patients with intestinal ileus, although we showed that these parameters were higher in patients who needed surgical treatment, upon the analysis done, we believe that it is not a clinically significant marker.

Artificial intelligence and the blood film: Performance of the MC-80 digital morphology analyzer in samples with neoplastic and reactive cell types.

Implementing artificial intelligence-based instruments in hematology laboratories requires evidence of efficiency in classifying pathological cells. In two-Universities, we assessed the performance of the Mindray® MC-80 for hematology patients with frequent leukemic and dysplastic cells. The Mindray MC-80® locates and pre-classifies cells in blood films. In a two-university study, four films were prepared from 591 samples, two each for the analyser MC-80 and the microscope reference method, using reagents from two different manufacturers. We used Microsoft Excel® statistics for imprecision and distributional inaccuracy and a matrix table model (H20-A2 CLSI standard) for sensitivity, specificity and predictive value for atypical cells. The results indicate minimal within-run imprecision (ICSH method) and good intra-method consistency even on duplicate analysis of 413 samples with a high incidence of hematological abnormalities (r = 0.942 or more, except for basophils, r = 0.841, and reactive lymphocytes, r = 0.847). Distributional inaccuracy was also very low compared to the microscope reference, with a pass rate higher than 80% for pathological cells (except 75.1% for reactive lymphocytes). The primary causes of discrepancy were bizarre shapes of dysplastic neutrophils and inconsistent nomenclature for lymphoma cells. Sensitivity for critical samples containing cells typically absent in circulating blood (immature or malignant) was 98.8% for immature granulocytes, 83.8% for all types of neoplastic cells, 93.6% for reactive lymphocytes and 97.5% for nucleated red blood cells. The negative predictive values of MC-80 were 98.8% for immature granulocytes, 88.4% for the different types of neoplastic cells, 97.8% for reactive lymphocytes, and 96.9% for nucleated red blood cells. Our study highlights the outstanding diagnostic performance of this artificial intelligence-based blood film analyzer for hematology patients with circulating abnormal cells. We appreciated the morphological harmonization of cells observed on the screen and those seen in the microscope.

Leukocyte Parameters and Immune Proteins Evolution during Prevention of Immune Insufficiency with an Extract of Moringa oleifera in Wistar Rats

Immunosuppression is a particular pathology reflecting a weakening of immune system and constituting a factor of exposure to other diseases. It is therefore both a disease and a risk factor. The aim of this work was to prevent a possible immune deficiency by using Moringa oleifera leaf extract. Forty eigth albino rats including 24 males and 24 females divided into 12 group weighing between 107g and 140g were used. Different doses of the leaves aqueous extract of Moringa oleifera respectively 200 mg/kg bw, 400 mg/kg bw, 800 mg/kg bw and 1600 mg/kg bw were compared with controls subjected to distilled water and 50 mg/kg bw of Levamisole for 14 days. At the end of this 14-day treatment, immunosuppression was achieved by intraperitoneal administration of 5 mg/kg bw of dexamethasone in all rats divided into groups for three days twice a day. Then a two-week observation was made to assess changes of the different immune cells after administration of dexamethasone. During the experiment, five samples were taken on day 1, day 14, day 17, day 21 and day 28. These different samples allowed the determination of hematological and immune proteins parameters. The obtained results showed an improvement in the immune status on day 14 with a highly significant increase (p<0,001) in white blood cells, a non-significant increase in neutrophils, lymphocytes, monocytes and immature granulocytes unlike the control subjected to distilled water. The administration of dexamethasone on day 17, total leukocytes in rats of group V and VI decreased in significantly. Contrarily controls and doses of 200 and 400 mg/kg bw. From day 21 to day 28, the levels of the various immune cells increased significantly. In conclusion, 800 mg/kg bw and 1600 mg/kg bw of aqueous extract have a good profile to prevent possible immune deficiency.

Evaluation of Intestinal Microbiota in Children With Sickle Cell Disease.

Sickle cell disease (SCD) is a chronic hemolytic anemia that may be life-threatening due to multisystemic effects. Identification of the factors which affect the pathophysiology of the disease is important in reducing mortality and morbidity. This study aimed to determine gut microbial diversity in children and adolescents with SCA compared with healthy volunteers and to evaluate the clinical impact of microbiota. The study included 34 children and young adolescents with SCD and 41 healthy volunteer participants. The microbiome was assessed by 16S rRNA sequencing in stool samples. Laboratory parameters of all participants, such as complete blood count and C-reactive protein values and clinical characteristics of SCD patients, were determined and compared, as well as clinical conditions of the patients, such as vascular occlusive crisis and/or acute chest syndrome, frequency of transfusions, intake of penicillin, hydroxyurea, and chelation therapy were recorded. White blood cell count, hemoglobin, immature granulocyte and C-reactive protein levels were significantly higher in the patient group ( P <0.05). Microbiota analysis revealed 3 different clusters among subjects; controls and 2 clusters in the SCD patients (patient G1 and G2 groups). Bacteroides spp. were more prevalent, while Dialester spp. and Prevotella spp. were less prevalent in SCD compared with controls ( t =2.142, P <0.05). Patient G2 (n=9) had a higher prevalence of Bacteroides and a lower prevalence of Prevotella than patient G1 (n=25). In our study, there was a difference between SCD patients and the control group, while 2 different microbiota profiles were encountered in SCD patients. This difference between the microbiota of the patients was not found to affect the clinical picture (such as vascular occlusive crisis, acute chest syndrome).