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Cancers Apr 2022Hairy cell leukemia (cHCL) patients have, in most cases, a specific clinical and biological presentation with splenomegaly, anemia, leukopenia, neutropenia,...
Hairy cell leukemia (cHCL) patients have, in most cases, a specific clinical and biological presentation with splenomegaly, anemia, leukopenia, neutropenia, monocytopenia and/or thrombocytopenia, identification of hairy cells that express CD103, CD123, CD25, CD11c and identification of the V600E mutation in the B-Raf proto-oncogene () in 90% of cases. Monocytopenia is absent in vHCL and SDRPL patients and the abnormal cells do not express CD25 or CD123 and do not present the mutation. Ten percent of cHCL patients are BRAF and the distinction between cHCL and HCL-like disorders including the variant form of HCL (vHCL) and splenic diffuse red pulp lymphoma (SDRPL) can be challenging. We performed deep sequencing in a large cohort of 84 cHCL and 16 HCL-like disorders to improve insights into the pathogenesis of the diseases. mutations were detected in 76/82 patients of cHCL (93%) and additional mutations were identified in Krüppel-like Factor 2 () in 19 patients (23%) or in 6 patients (7.5%). Some genetic alterations were localized on the cytidine deaminase (AID) consensus motif, suggesting AID-induced mutations. When analyzing sequential samples, a clonal evolution was identified in half of the cHCL patients (6/12 pts). Among the 16 patients with HCL-like disorders, we observed an enrichment of mutations in vHCL/SDRPL (3/5 pts) and genes involved in the epigenetic regulation () (3/5 pts). Furthermore, mutations were associated with a bad prognosis and a shorter time to next treatment (TTNT) and progression-free survival (PFS), independently of the HCL classification.
PubMed: 35454811
DOI: 10.3390/cancers14081904 -
Frontiers in Immunology 2024Micronutrients, such as vitamins and trace minerals, are critical for supporting growth, performance, health and maintaining redox balance. Zinc (Zn), an essential... (Review)
Review
Micronutrients, such as vitamins and trace minerals, are critical for supporting growth, performance, health and maintaining redox balance. Zinc (Zn), an essential micronutrient, aids the functioning of innate and adaptive immune cells. This scoping review aims to assemble and evaluate the evidence available for the role of Zn within calf immunity. Relevant literature was identified within Web of Science, PubMed, and CABI using search terms specific to the major innate and adaptive immune cell populations. There was no evidence that Zn supplementation altered neutrophil, natural killer cell, or T-cell functions. However, there was limited evidence to support Zn supplementation with reduced monocyte numbers, but there was no evidence to associate the monocytopenia with improvements in monocyte function. There is moderate evidence to suggest that Zn supplementation was beneficial for maintaining epithelial barriers of integumental and mucosal surfaces. The evidence supports supplementation above the current industry recommendations for improving immunoglobulin (Ig) production, with the strongest results being observed for IgG and IgM. Moreover, Zn supplementation was associated with reduced proinflammatory cytokine production, which may reduce inflammation-associated hypophagia and warrants further investigation. Furthermore, Zn reduced the duration of clinical signs in animals facing respiratory disease and diarrhea. However, consensus is needed about the optimal dose, route, and Zn formulation most appropriate for supporting immunity. In conclusion, while the literature supports that Zn could enhance calf immunity, there is insufficient evidence to adequately determine the extent to which Zn impacts innate immune cell and T-cell functions. Determination of the immune cell functions susceptible to modification by Zn supplementation is an important knowledge gap for enhancing the understanding of Zn and calf immunity.
Topics: Zinc; Animals; Cattle; Dietary Supplements; Immunity, Innate; Adaptive Immunity
PubMed: 38799472
DOI: 10.3389/fimmu.2024.1387950 -
International Journal of Health Sciences Oct 2016The neoplasm is still a potential threat for breast, Non-Small Cell Lung (NSCL) and cervix cancer patients. Those gradually invade into other body organs, inducing...
BACKGROUND
The neoplasm is still a potential threat for breast, Non-Small Cell Lung (NSCL) and cervix cancer patients. Those gradually invade into other body organs, inducing complex pathological complications. Whereas, the anticancer drugs suppress the bone marrow, resulting serious hematological toxicities. Thus, the monocytic toxicity may the chance of infections, particularly in AID's patients.
OBJECTIVE
We aimed this retrospective study to investigate the monocytopenia induced by vinorelbine following chemotherapy in cancer patients.
PATIENTS AND METHOD
A total 60 adult cancer patients were divided into two groups; Group-1 patients received the treatment of Vinorelbine alone while group 2 patients received Vinorelbine based combination chemotherapy.
RESULT
The overall comparison of mean monocyte count (×10 per μl) with time showed a significant statistical difference ( value <0.001) for G-I and no significant difference for G-II ( value <0.08). The independent comparison of mean values for two groups at every week confirms the non-significant statistical difference during all of the five weeks ( values 0.551, 0.112, 0.559, 0.372, 0.468 respectively). In addition of that, the comparison of mean values observed before therapy with that of week 4 (after therapy) showed significant difference in G-I ( value <0.001) and non-significant in G-II ( value 0.053).
CONCLUSION
Monocytopenia is induced in both of the chemotherapy protocols allows the clinical oncologists and consultant physicians to select either of the chemotherapy protocol. The therapeutic efficacy should constitute the intervening consideration to treat the breast, cervix and NSCL (Non-Small Cell Lung's) cancers.
PubMed: 27833519
DOI: No ID Found -
Journal of Family Medicine and Primary... May 2022This study explored the role of various laboratory biomarkers on inflammatory indices for predicting disease progression toward severity in COVID-19 patients.
BACKGROUND AND OBJECTIVE
This study explored the role of various laboratory biomarkers on inflammatory indices for predicting disease progression toward severity in COVID-19 patients.
METHODS
This retrospective study was conducted on 1233 adults confirmed for COVID-19. The participants were grouped undermild, moderate, and severe grade disease. Serum bio-inflammatory index (SBII) and systemic inflammatory index (SII) were calculated and correlated with disease severity. The study variables, including clinical details and laboratory variables, were analyzed for impact on the inflammatory indices and severity status using a sequential multiple regression model to determine the predictors for mortality. Receiver operating characteristics defined the cut-off values for severity.
RESULTS
Among the study population, 56.2%, 20.7%, and 23.1% were categorized as mild, moderate, and severe COVID-19 cases. Diabetes with hypertension was the most prevalent comorbid condition. The odds for males to have the severe form of the disease was 1.6 times (95% CI = 1.18-2.18, = 0.002). The median (inter-quartile-range) of SBII was 549 (387.84-741.34) and SII was 2097.6 (1113.9-4153.73) in severe cases. Serum urea, electrolytes, gamma-glutamyl transferase, red-cell distribution width-to-hematocrit ratio, monocytopenia, and eosinopenia exhibited a significant influence on the SpO, SBII, and SII. Both SBII (r = -0.582, < 0.001) and SII (r = -0.52, < 0.001) strongly correlated inversely with SpO values [Figures 3a and 3b]. More than 80% of individuals admitted with severe grade COVID-19 had values of more than 50 percentile of SBII and SII. The sensitivity and specificity of SBII at 343.67 for severity were 81.4% and 70.1%, respectively. SII exhibited 77.2% sensitivity and 70.8% specificity at 998.72.
CONCLUSION
Serial monitoring of the routinely available biomarkers would provide considerable input regarding inflammatory status and severity progression in COVID-19.
PubMed: 35800567
DOI: 10.4103/jfmpc.jfmpc_2014_21 -
Blood Cancer Journal Mar 2017Current prognostic models for myelodysplastic syndromes (MDS), including the Revised International Prognostic Scoring System (IPSS-R), do not account for host immunity....
Current prognostic models for myelodysplastic syndromes (MDS), including the Revised International Prognostic Scoring System (IPSS-R), do not account for host immunity. We retrospectively examined the prognostic relevance of monocytopenia, lymphocytopenia and lymphocyte-to-monocyte ratio (LMR) in a cohort of 889 patients with primary MDS. After a median follow-up of 27 months, 712 (80%) deaths and 116 (13%) leukemic transformation were documented. In univariate analysis, subnormal absolute lymphocyte count (ALC) <0.9 × 10/l; P=0.001), ALC<1.2 × 10/l (P=0.0002), subnormal absolute monocyte count (AMC) <0.3 × 10/l (P=0.0003), LMR (P⩽0.0001) and LMR⩾5 (P=0.03) were all associated with inferior overall survival. In multivariable analysis that included other risk factors, significance was retained for LMR (P=0.02) and became borderline for ALC <1.2 × 10/l (P=0.06). Analysis in the context of IPSS-R resulted in P-values of 0.06 for ALC<1.2 × 10/l, 0.7 for monocytopenia and 0.2 for LMR. Leukemia-free survival was not affected by ALC, AMC or LMR. The observations from the current study suggest a possible detrimental role for altered host immunity in primary MDS, which might partly explain the therapeutic benefit of immune-directed therapy, including the use of immune modulators; however, IPSS-R-independent prognostic value for either ALC or AMC was limited.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Marrow; Female; Humans; Leukocyte Count; Lymphocytes; Lymphopenia; Male; Middle Aged; Monocytes; Myelodysplastic Syndromes; Prognosis; Retrospective Studies; Survival Analysis; Young Adult
PubMed: 28362440
DOI: 10.1038/bcj.2017.30 -
Heliyon Jun 2022In Covid-19, profound systemic inflammatory responses are accompanied by both metabolic risk factors for severity and, separately, metabolic mechanisms have been shown...
BACKGROUND
In Covid-19, profound systemic inflammatory responses are accompanied by both metabolic risk factors for severity and, separately, metabolic mechanisms have been shown to underly disease progression. It is unknown whether this reflects similar situations in sepsis or is a unique characteristic of Covid-19.
AIMS
Define the immunometabolic signature of Covid-19.
METHODS
65 patients with Covid-19,19 patients with sepsis and 14 healthy controls were recruited and sampled for plasma, serum and peripheral blood mononuclear cells (PBMCs) through 10 days of critical illness. Metabotyping was performed using the Biocrates p180 kit and multiplex cytokine profiling undertaken. PBMCs underwent phenotyping by flow cytometry. Immune and metabolic readouts were integrated and underwent pathway analysis.
RESULTS
Phopsphatidylcholines (PC) are reduced in Covid-19 but greater than in sepsis. Compared to controls, tryptophan is reduced in Covid-19 and inversely correlated with the severity of the disease and IFN-ɣ concentrations, conversely the kyneurine and kyneurine/tryptophan ratio increased in the most severe cases. These metabolic changes were consistent through 2 pandemic waves in our centre. PD-L1 expression in CD8+ T cells, Tregs and CD14+ monocytes was increased in Covid-19 compared to controls.
CONCLUSIONS
In our cohort, Covid-19 is associated with monocytopenia, increased CD14+ and Treg PD-L1 expression correlating with IFN-ɣ plasma concentration and disease severity (SOFA score). The latter is also associated with metabolic derangements of Tryptophan, LPC 16:0 and PCs. Lipid metabolism, in particular phosphatidylcholines and lysophosphatidylcolines, seems strictly linked to immune response in Covid-19. Our results support the hypothesis that IFN-ɣ -PD-L1 axis might be involved in the cytokine release syndrome typical of severe Covid-19 and the phenomenon persisted through multiple pandemic waves despite use of immunomodulation.
PubMed: 35774516
DOI: 10.1016/j.heliyon.2022.e09733 -
Blood Jul 2016Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2...
Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin(-)Sca-1(+)Kit(+) cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte-related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation.
Topics: Animals; Cell Differentiation; Dendritic Cells; GATA2 Transcription Factor; GATA3 Transcription Factor; Hepatocyte Nuclear Factor 1-alpha; Mice; Mice, Knockout; Myeloid Cells; T-Lymphocytes
PubMed: 27259979
DOI: 10.1182/blood-2016-02-698118 -
Acta Informatica Medica : AIM : Journal... Mar 2023Coronavirus disease 2019 (COVID-19) can cause a wide clinical spectrum, ranging from asymptomatic to severe disease with a high mortality rate. In view of the current...
BACKGROUND
Coronavirus disease 2019 (COVID-19) can cause a wide clinical spectrum, ranging from asymptomatic to severe disease with a high mortality rate. In view of the current pandemic and the increasing influx of patients into healthcare facilities, there is a need to identify simple and reliable tools for stratifying patients.
OBJECTIVE
Study aimed to analyze whether hemogram-derived ratios (HDRs) can be used to identify patients with a risk of developing a severe clinical form and admission to hospital.
METHODS
This cross-sectional and observational study included 500 patients with a confirmed diagnosis of COVID-19. Data on clinical features and laboratory parameters were collected from medical records and 13 HDRs were calculated and analyzed. Descriptive and inferential statistics were included in the analysis.
RESULTS
Of the 500 patients, 43.8% had a severe form of the disease. Lymphocytopenia, monocytopenia, higher C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were found in severe patients ( < 0.05). Significantly higher neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-platelet ratio (NPR), neutrophil-to-lymphocyte-to-platelet ratio (NLPR) and CRP-to-lymphocyte ratio (CRP/Ly) values were found in severe patients ( < 0.001). In addition, they have statistically significant prognostic potential ( < 0.001). The area under the curve (AUC) for CRP/Ly, dNLR, NLPR, NLR, and NPR were 0.693, 0.619, 0.619, 0.616, and 0.603, respectively. The sensitivity and specificity were 65.7% and 65.6% for CRP/Ly, 51.6% and 70.8 for dNLR, 61.6% and 57.3% for NLPR, 40.6% and 80.4% for NLR, and 48.8% and 69.1% for NPR.
CONCLUSION
The results of the study suggest that NLR, dNLR, CRP/Ly, NPR, and NLPR can be considered as potentially useful markers for stratifying patients with a severe form of the disease. HDRs derived from routine blood tests results should be included in common laboratory practice since they are readily available, easy to calculate, and inexpensive.
PubMed: 37038490
DOI: 10.5455/aim.2023.31.41-47 -
PloS One 2016Granulomas are a collection of immune cells considered to be protective in infectious diseases. The in vitro generation of granulomas is an interesting substitution to...
Granulomas are a collection of immune cells considered to be protective in infectious diseases. The in vitro generation of granulomas is an interesting substitution to invasive approaches of granuloma study. The monitoring of immune response through the determination of in vitro granuloma formation in patients with severe sepsis may be critical to individualize treatments. We compared the in vitro generation of granulomas by co-culturing circulating mononuclear cells from 19 patients with severe sepsis, 9 patients cured from Q fever and 12 healthy subjects as controls, and Sepharose beads coated either with BCG or Coxiella burnetii extracts to analyze both immune and innate granulomas, respectively. We showed that the great majority of patients with severe sepsis were unable to form granulomas in response to BCG and C. burnetii extracts whereas more than 80% of healthy controls and patients cured from Q fever formed granulomas. We also found that monocytopenia and defective production of tumor necrosis factor were associated with reduced formation of granulomas in patients with severe sepsis even if TNF did not seem to be involved in the defective granuloma formation. Taken together, these results suggest that the deficiency of granuloma formation may be a measurement of altered recruitment and activation of monocytes and lymphocytes in patients with severe sepsis.
Topics: Aged; Case-Control Studies; Cytokines; Female; Granuloma; Humans; Lymphocytes; Male; Middle Aged; Monocytes; Q Fever; Sepsis
PubMed: 27441846
DOI: 10.1371/journal.pone.0158528 -
Acta Veterinaria Scandinavica Mar 2021In cows with acute toxic mastitis (ATM), the leukogram aids in the assessment of the severity of disease. The goal of our study was to compare the leukogram of 158 cows...
BACKGROUND
In cows with acute toxic mastitis (ATM), the leukogram aids in the assessment of the severity of disease. The goal of our study was to compare the leukogram of 158 cows with ATM (cases) and 168 clinically healthy cows (controls). We hypothesised that the leukograms of surviving and non-surviving cows differ and that there are variables of the leukogram with sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM. The cows were examined clinically and underwent haematological and biochemical examination of blood and bacteriological culture of milk samples.
RESULTS
All cows with ATM had a poor appetite or anorexia, and 34 cows (21.5%) were recumbent. A single quarter was affected in 119 cows (75.3%), two quarters in 37 cows (23.4%) and three quarters in two cows (1.3%). Bacteriological culture showed Gram-negative pathogens in 100 cows (63.3%), Gram-positive in 15 (9.5%) and yeast in 4 (2.5%). The median total leukocyte count of cases was 4300 cells/µL (interquartile range = 2300-8200/µL), which was significantly lower than 8000 cells/µL (6525-9300/µL) in controls. Except for band neutrophils and metamyelocytes, the counts of all components of the leukogram were lower in cases compared with controls. Significantly more cows with ATM had leukopenia (60.1 vs. 4.1%) or leukocytosis (10.1 vs. 3.0%) than controls. Diseased cows had significantly lower segmented neutrophil counts than controls (860 vs. 2598 cells/µL), and 69.5 and 17.3%, respectively, had counts below the reference interval. Cases had increased band (77.3%) and metamyelocyte (25.0%) counts compared with controls (0.6 and 0%, respectively). In diseased cows, eosinopenia occurred in 66.4% (controls, 1.8%), monocytopenia in 40.6% (4.2%) and lymphopenia in 60.2% (1.8%). Twenty-one diseased cows (16.4%) had a regenerative and 57 (44.5%) had a degenerative left shift. The median neutrophil-to-lymphocyte ratio was 0.97 in diseased cows and 0.63 in controls. Toxic changes in neutrophils including cytoplasmic basophilia and vacuolisation were seen in 101 (91.8%) of 110 blood smears of diseased cows. The leukogram of the surviving and non-surviving cows did not differ significantly, and the hypothesis was rejected.
CONCLUSIONS
ATM results in severe changes in the leukogram particularly leukopenia, lymphopenia, and degenerative left shift. The hypothesis that the leukograms of surviving and non-surviving cows differ was rejected. The leukogram has not sufficient prognostic potential to be used in the decision to treat or not to treat a cow with ATM.
Topics: Animals; Cattle; Dairying; Female; Leukocyte Count; Mastitis, Bovine; Predictive Value of Tests
PubMed: 33712040
DOI: 10.1186/s13028-021-00576-0