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Cancer Management and Research 2023Platelet distribution width (PDW) is a marker of platelet anisocytosis that increases with platelet activation. The clinical implications of PDW in HCC are not...
BACKGROUND
Platelet distribution width (PDW) is a marker of platelet anisocytosis that increases with platelet activation. The clinical implications of PDW in HCC are not well-defined. This study aimed to determine whether PDW could predict recurrence in patients with HCC after resection.
METHODS
Between January and December 2008, 471 patients with HCC were recruited retrospectively. The clinicopathological characteristics of patients with HCC were analyzed based on the relationship between the two PDW groups. Kaplan-Meier curves and multivariate Cox regression analyses were used to evaluate the relationship between PDW and disease-free survival (DFS). A novel nomogram was developed based on the identified independent risk factors. Its accuracy was evaluated using a calibration curve and concordance index. The predictive value was evaluated using a receiver operating characteristic (ROC) curve.
RESULTS
PDW was significantly associated with direct bilirubin, total bilirubin, urea, and prothrombin time. Patients with PDW ≥ 17.1 were a significantly shorter DFS than those with PDW < 17.1 (17.98% vs 49.83%, < 0.001). Multivariate analysis determined that alpha-fetoprotein (AFP), carcinoembryonic antigen, microvascular invasion (MVI), tumor size, and tumor number were the independent variables associated with DFS. Patients with PDW ≥ 17.1 had a hazard ratio of 1.381 (95% confidence interval: 1.069-1.783, = 0.014) for DFS. AFP, PDW, MVI, tumor size, and tumor number were identified as preoperative independent risk factors for DFS and used to establish the nomogram. Calibration curve analysis revealed that the standard curve fitted well with the predicted curve. ROC curve analysis demonstrated the high efficiency of the nomogram.
CONCLUSION
Increased PDW may predict recurrence-free survival in patients with HCC. Our nomogram model also performed well in predicting patient prognoses.
PubMed: 37337478
DOI: 10.2147/CMAR.S408548 -
Hematology, Transfusion and Cell Therapy 2022The myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular...
INTRODUCTION
The myelodysplastic syndrome (MDS) represents a group of hematopoietic neoplasms that is characterized by clonal hematopoiesis, cytopenia and abnormal cellular maturation. Red cell distribution width (RDW) refers to the variation degree of erythrocyte size and it is a reflection of anisocytosis. Higher values have been linked to adverse outcomes, such as increased mortality, vascular events, kidney and liver disease and demonstrated to harbor poor prognosis in solid and hematological malignancies. The RDW value can be used as a contributing parameter for MDS diagnosis, as well as its prognosis. In this study, we essentially aimed to demonstrate the correlation between the RDW and MDS prognostic indexes.
MATERIALS AND METHODS
Ninety-four MDS patients at the Aydın Adnan Menderes University Hematology Division were included in the study. The correlations between the RDW and laboratory values (either lactate dehydrogenase, albumin, globulin or ferritin) and the RDW prognostic scoring indexes (IPSS, WPSS, IPSS-R and LR-PSS) were investigated. The PASW for Windows, version 21.0 (SPSS Inc., Chicago, IL, USA), was used for statistical assessment. A p-value below 0.05 was the cut-off for the statistical significance.
RESULTS
The mean age of all the patients was 73 ± 10 years. Patients were observed for 41.88 ± 25 months. The mean RDW value for all cases was 15.5 ± 2.39. We found a statistically significant difference of survival between RDW values below and above 15.5% (p = 0.016). A significant difference was also observed according to the prognostic scoring indexes (see below).
CONCLUSION
An increase in RDW is probably related to dysplasia in the MDS and this constitutes a possible explanation for the poor outcome. Prognostic indexes might incorporate the RDW as a parameter in the future.
PubMed: 33583768
DOI: 10.1016/j.htct.2020.11.007 -
Cureus Mar 2023Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts expressing platelet-specific surface...
Acute megakaryoblastic leukemia (AMKL) is a rare subtype of acute myeloid leukemia (AML) characterized by abnormal megakaryoblasts expressing platelet-specific surface antigens. 4%-16% of childhood AMLs are AMKL. Childhood AMKL is usually associated with Down syndrome (DS). It is 500 times more common in patients with DS when compared to the general population. In contrast, non-DS-AMKL is much rarer. We describe a case of de novo non-DS-AMKL in a teenage girl child who presented with a history of excessive tiredness, fever, abdominal pain for three months, and vomiting for four days. She had lost appetite, and weight. On examination she was pale; there was no clubbing, hepatosplenomegaly or lymphadenopathy. There were no dysmorphic features or neurocutaneous markers. Laboratory tests showed bicytopenia (Hb: 6.5g/dL, total WBC count: 700/µL, platelet count: 216,000/ µL, Reticulocyte %: 0.42) and 14% blasts on the peripheral blood smear. Platelet clumps and anisocytosis were also noted. Bone marrow aspirate showed a few hypocellular particles with dilute cell trails but showed 42% blasts. Mature megakaryocytes showed marked dyspoiesis. Flow cytometry on bone marrow aspirate showed myeloblasts and megakaryoblasts. Karyotyping showed 46 XX. Hence, a final diagnosis of non-DS-AMKL was established. She was treated symptomatically. However, she was discharged on request. Interestingly, the expression of erythroid markers such as CD36 and lymphoid markers like CD7 is usually seen in DS-AMKL and not in non-DS-AMKL. AMKL is treated with AML-directed chemotherapies. Although complete remission rates are similar to other AML subtypes, overall survival is only about 18-40 weeks.
PubMed: 36911590
DOI: 10.7759/cureus.35965 -
Veterinary Research Communications Apr 2024South American camelids (SACs) play an increasing role in veterinary care in Europe. Many alpacas or llamas presented to veterinarians suffer from anaemia, regularly... (Review)
Review
South American camelids (SACs) play an increasing role in veterinary care in Europe. Many alpacas or llamas presented to veterinarians suffer from anaemia, regularly with a packed cell volume (PCV) below 0.10 l/l, which is a life-threatening condition for the animals. This review article presents clinical and laboratory diagnostic tools for the diagnosis of anaemia in SACs. Clinical identification of anaemic animals can be performed by assessing the FAMACHA© score and the Body Condition Score (BCS), since anaemia in alpacas and llamas correlates with pale mucous membranes and a lowered BCS. Haematological examination of a blood sample can provide a more differentiated diagnosis of anaemia in SACs. A common finding is regenerative anaemia with an increased number of reticulocytes that is often caused by blood loss due to Haemonchus contortus. Changes in a blood smear from an alpaca or llama with regenerative anaemia may include normoblasts (nucleated red blood cells), anisocytosis, poikilocytosis, polychromasia, Howell-Jolly bodies or basophilic stippling. Furthermore, non-regenerative anaemia, often caused by trace element deficiency or cachexia, can also occur.
Topics: Animals; Camelids, New World; Anemia; Haemonchus; South America
PubMed: 38049672
DOI: 10.1007/s11259-023-10274-z -
Diagnostic Pathology Oct 2020Histologic features of idiopathic non-cirrhotic portal hypertension (INCPH) may overlap with those without INCPH. Recently, these features have been recognized as part...
BACKGROUND
Histologic features of idiopathic non-cirrhotic portal hypertension (INCPH) may overlap with those without INCPH. Recently, these features have been recognized as part of the larger spectrum of porto-sinusoidal vascular disease (PSVD). We assessed interobserver agreement on histologic features that are commonly associated with INCPH and studied whether a provision of relevant clinical history improves interobserver agreement.
METHODS
The examined histologic features include lobular (such as anisocytosis, nodular regeneration, sinusoidal dilatation, increased parenchymal draining veins, and incomplete fibrous septa) and portal tract changes (such as paraportal shunting vessel(s), portal tract remnant, increased number of portal vessels, and obliterative portal venopathy). Thirty-four archived liver samples from patients with (group A) and without (group B) INCPH were retrieved. A total of 90 representative images of lobules (L) and portal tracts (P) were distributed among 9 liver pathologists blinded to true clinical history. Each pathologist answered multiple choice questions based on the absence (Q1) or presence (Q2) of clinical history of portal hypertension. Fleiss' kappa coefficient analysis (unweighted) was performed to assess interobserver agreement on normal versus abnormal diagnosis, in L and P, based on Q1 and Q2.
RESULTS
The kappa values regarding normal versus abnormal diagnosis were 0.24, 0.24, 0.18 and 0.18 for L-Q1, L-Q2, P-Q1, and P-Q2, respectively. With true clinical history provided, the kappa values were L- 0.32, P-0.17 for group A and L-0.12, P-0.14 for group B. Four pathologists changed their assessments based on the provided history. Interobserver agreement on the interpretation of L and P as normal versus abnormal was slight to fair regardless of provision of clinical history.
CONCLUSIONS
Our findings indicate that the histologic features of INCPH/PSVD are not limited to patients with portal hypertension and are subject to significant interobserver variation.
Topics: Adolescent; Adult; Aged; Female; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Observer Variation; Pathologists; Young Adult
PubMed: 33097074
DOI: 10.1186/s13000-020-01049-0 -
International Journal of Molecular... May 2022Prime editing was used to insert and correct various pathogenic mutations except for beta-thalassemia variants, which disrupt functional beta-globin and prevent...
Prime editing was used to insert and correct various pathogenic mutations except for beta-thalassemia variants, which disrupt functional beta-globin and prevent hemoglobin assembly in erythrocytes. This study investigated the effect of gene correction using prime editor version 3 (PE3) in a mouse model with the human beta-thalassemia IVS-II-654 mutation (C > T). The T conversion generates a 5′ donor site at intron 2 of the beta-globin gene resulting in aberrant splicing of pre-mRNA, which affects beta-globin expression. We microinjected PE3 components (pegRNA, nick sgRNA, and PE2 mRNA) into the zygotes from IVS-II-654 mice to generate mutation-edited mice. Genome sequencing of the IVS-II-654 site showed that PE3 installed the correction (T > C), with an editing efficiency of 14.29%. Reverse transcription-PCR analysis showed that the PE3-induced conversion restored normal splicing of beta-globin mRNA. Subsequent comprehensive phenotypic analysis of thalassemia symptoms, including anemic hematological parameters, anisocytosis, splenomegaly, cardiac hypertrophy, extramedullary hematopoiesis, and iron overload, showed that the corrected IVS-II-654 mice had a normal phenotype identical to the wild type mice. Off-target analysis of pegRNA and nick sgRNA additionally showed the genomic safety of PE3. These results suggest that correction of beta-thalassemia mutation by PE3 may be a straightforward therapeutic strategy for this disease.
PubMed: 35682629
DOI: 10.3390/ijms23115948 -
JFMS Open Reports 2019A 5-year-old neutered male domestic shorthair cat presented with an 18-month history of facial tics, and progressive general ataxia, weakness, lethargy and anorexia of 2...
CASE SUMMARY
A 5-year-old neutered male domestic shorthair cat presented with an 18-month history of facial tics, and progressive general ataxia, weakness, lethargy and anorexia of 2 weeks' duration. MRI of the brain showed a well-defined heterogeneous hyperintense mass on T1-weighted and T2-weighted images, with central hypointensity in the rostral commissure and septum pellucidum, and perilesional hyperintensity in fluid-attenuated inversion recovery, suggestive of perilesional oedema. Gross examination in a transverse section of the brain at the level of the septum pellucidum revealed a 0.2 cm brown soft mass. Histopathological examination identified a biphasic neoplastic proliferation of mesenchymal and neuroepithelial cell populations. Fusiform cells were predominately distributed in bundles showing a high degree of anisocytosis and marked immune-positive reaction to vimentin immunochemistry, confirming a sarcomatous origin. Additionally, high numbers of astrocytic cells were identified by an intense immunopositive reaction to glial fibrillary acidic protein and negative reaction to oligodendrocyte transcription factor 2 immunochemistry. Vascular invasion of the neoplasia into the wall of a medium branch of the rostral cerebral artery was present (secondary Scherer structures). Based on these characteristics, the tumour was defined as a gliosarcoma. Gliosarcoma is a recognised astrocytoma grade IV anaplastic glial cell tumour with sarcomatous differentiation.
RELEVANCE AND NOVEL INFORMATION
To our knowledge, this is the first report describing a cerebral gliosarcoma in a cat including clinical, MRI, macroscopic and histopathological features and immunolabelling characteristics.
PubMed: 31636916
DOI: 10.1177/2055116919879783 -
Polish Archives of Internal Medicine Nov 2023Risk prediction in patients with heart failure with reduced ejection fraction (HFrEF) is one of the key challenges for clinicians. Novel biomarkers aggregating several...
Long-term prognostic scores may underestimate the risk of death in patients with heart failure with reduced ejection fraction in whom red cell distribution width is elevated.
INTRODUCTION
Risk prediction in patients with heart failure with reduced ejection fraction (HFrEF) is one of the key challenges for clinicians. Novel biomarkers aggregating several important pathophysiological pathways may modify the diagnostic discrimination of validated scores. The red cell distribution width (RDW) is a cheap and easily available measure of anisocytosis, and was shown to have a strong independent prognostic power in short- and medium‑term prognosis in HFrEF.
OBJECTIVES
Our aim was to assess the prognostic power of RDW in optimally treated chronic HFrEF, and to investigate whether different RDW may impact the prognostic accuracy of validated long‑term scores in HFrEF.
PATIENTS AND METHODS
The study included 551 patients at a median (interquartile range [IQR]) age of 54 (47-59) years, of whom 86.6% were men. The patients represented the median New York Heart Association class III (IQR, II-III), and ischemic etiology occurred in 56.6% of the cases. In all patients, RDW as a coefficient of variation was calculated, along with Meta‑Analysis Global Group in Chronic Heart Failure Score (MAGGIC‑HF) and Seattle Heart Failure Survival Model (SHFSM).
RESULTS
The patients were followed for 5 years and all‑cause mortality was assessed. We recorded 166 (30.1%) and 225 (40.8%) deaths at 3 and 5 years, respectively. Scores based on MAGGIC‑HF and SHFSM algorithms for the respective prediction of 3- and 5‑year mortality were calculated for each patient and compared with the observed mortality. There was a significant underestimation of mortality in the patients with RDW above 15.4% (reference values, 11.5%-14.5%), while in those with lower RDW SHFSM overestimated the actual risk. The excess mortality in the higher RDW group was confirmed by the Hosmer-Lemeshow statistic.
CONCLUSIONS
The RDW has a strong prognostic value in chronic HFrEF, independently of the risk assessed by the MAGGIC‑HF or the SHFSM score.
Topics: Female; Humans; Male; Middle Aged; Biomarkers; Erythrocyte Indices; Heart Failure; Prognosis; Retrospective Studies; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 37162185
DOI: 10.20452/pamw.16494 -
Annals of Palliative Medicine Aug 2022Red blood cell distribution width (RDW) could reflect interleukin-6 (IL-6) systemic activity since anisocytosis represents the inhibition of erythropoiesis, leaded by... (Observational Study)
Observational Study
BACKGROUND
Red blood cell distribution width (RDW) could reflect interleukin-6 (IL-6) systemic activity since anisocytosis represents the inhibition of erythropoiesis, leaded by the hyperinflammatory background. Our objective was to analyze RDW performance to predict outcome in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS).
METHODS
Retrospective observational study including 173 patients with COVID-19-associated ARDS. Data was analyzed at hospital admission, inclusion in the TOCICOV Study (day 0), days 1, 3, 7 and 15 post-inclusion.
RESULTS
Overall, 57% patients received tocilizumab. Overall mortality was 20.8%. RDW was higher in non-survivors compared to survivors at admission (13.53% vs. 14.35, P=0.0016), day 0 (13.60% vs. 14.42, P=0.026), day 3 (13.43% vs. 14.36, P<0.001) and day 7 (13.41% vs. 14.31, P=0.046), presenting better discrimination ability for mortality than other prognostic markers [area under the curve-receiver operating characteristic (AUC-ROC) =0.668 for admission RDW, 0.680 for day 0 RDW, 0.695 for day 3 RDW and 0.666 for day 7 RDW]. RDW values did not vary significantly according to tocilizumab treatment. When adjusted by hemoglobin and tocilizumab treatment, only RDW at admission, day 0, day 3 and C reactive protein (CRP) at day 0 and day 1 were associated with mortality (P<0.05). Only in non-tocilizumab treated patients, IL-6 levels at day 0 were correlated with day 3 RDW (r=0.733, P=0.004) and with day 3 CRP (r=0.727, P=0.022). Both parameters showed significant statistical correlation (r=0.255 for day 1 RDW and CRP in the overall cohort and r=0.358 for day 3 RDW and CRP in patients not treated with tocilizumab, P<0.015).
CONCLUSIONS
RDW predicts COVID-19-associated ARDS mortality and reflects the hyperinflammatory background and the effects of cytokines such as IL-6, irrespective of tocilizumab treatment.
Topics: Biomarkers; C-Reactive Protein; COVID-19; Erythrocyte Indices; Erythrocytes; Humans; Interleukin-6; Prognosis; Respiratory Distress Syndrome; Retrospective Studies
PubMed: 35610196
DOI: 10.21037/apm-22-119 -
JCI Insight Sep 2022Increased red cell distribution width (RDW), which measures erythrocyte mean corpuscular volume (MCV) variability (anisocytosis), has been linked to early mortality in...
Increased red cell distribution width (RDW), which measures erythrocyte mean corpuscular volume (MCV) variability (anisocytosis), has been linked to early mortality in many diseases and in older adults through unknown mechanisms. Hypoxic stress has been proposed as a potential mechanism. However, experimental models to investigate the link between increased RDW and reduced survival are lacking. Here, we show that lifelong hypobaric hypoxia (~10% O2) increased erythrocyte numbers, hemoglobin, and RDW, while reducing longevity in male mice. Compound heterozygous knockout (hKO) mutations in succinate dehydrogenase (Sdh; mitochondrial complex II) genes Sdhb, Sdhc, and Sdhd reduced Sdh subunit protein levels, reduced RDW, and increased healthy life span compared with WT mice in chronic hypoxia. RDW-SD, a direct measure of MCV variability, and the SD of MCV showed the most statistically significant reductions in Sdh hKO mice. Tissue metabolomic profiling of 147 common metabolites showed the largest increase in succinate with elevated succinate/fumarate and succinate/oxoglutarate (2-ketoglutarate) ratios in Sdh hKO mice. These results demonstrate that mitochondrial complex II level is an underlying determinant of both RDW and healthy life span in hypoxia and suggest that therapeutic targeting of Sdh might reduce high RDW-associated clinical mortality in hypoxic diseases.
Topics: Animals; Erythrocyte Indices; Hypoxia; Longevity; Male; Mice; Succinate Dehydrogenase; Succinates
PubMed: 35881479
DOI: 10.1172/jci.insight.158737