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Cancers May 2022Alectinib is a standard initial treatment for patients with advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). The current study...
Alectinib is a standard initial treatment for patients with advanced anaplastic lymphoma kinase (ALK) rearranged non-small-cell lung cancer (NSCLC). The current study analyzed a prospective cohort of 24 consecutive alectinib-treated patients and controls in order to comprehensively characterize longitudinal erythrocyte changes under treatment with ALK inhibitors. Upon starting alectinib, all examined patients developed reticulocytosis and abnormal erythrocyte morphology with anisocytosis and a predominance of acanthocytes (64% of red blood cells on average, range 36−100%) in the peripheral blood smear within approximately 2 weeks. Changes were accompanied by a gradual reduction in Eosin-5-maleimide (EMA) binding, which became pathologic (<80% of cells) within 1−2 months in all cases, mimicking an abortive form of hereditary spherocytosis. The latter could be ruled out in 3/3 of analyzed cases by normal sequencing results for the ANK1, EPB42, SLC4A1, SPTA1, or SBTB genes. The direct Coombs test was also negative in 11/11 tested cases. Besides, anemia, increased LDH, and increased bilirubin were noted in a fraction of patients only, ranging between 42 and 68%. Furthermore, haptoglobin decreases were infrequent, occurring in approximately 1/3 of cases only, and mild, with an average value of 0.93 g/L within the normal range of 0.3−2 g/dL, suggesting that hemolysis occurred predominantly in the extravascular compartment, likely due to splenic trapping of the deformed erythrocytes. These changes showed no association with progression-free survival under alectinib or molecular features, i.e., ALK fusion variant or TP53 status of the disease, and resolved upon a switch to an alternative ALK inhibitor. Thus, alectinib induces mild, reversible erythrocyte changes in practically all treated patients, whose most sensitive signs are aberrant red cell morphology in the peripheral smear, a pathologic EMA test, and reactive reticulocytosis. Frank hemolytic anemia is rare, but mild subclinical hemolysis is very frequent and poses differential-diagnostic problems. Alectinib can be continued under the regular control of hemolysis parameters, but the risk of long-term complications, such as cholelithiasis due to increased serum bilirubin in most patients, remains unclear at present.
PubMed: 35681698
DOI: 10.3390/cancers14112720 -
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 -
PLoS Pathogens May 2022Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted...
Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted mutagenesis methods are yet to be developed to define genes essential for these pathogens. In addition, vaccines conferring protection against diseases caused by Anaplasma species are not available. Here, we describe a targeted mutagenesis method for deletion of the phage head-to-tail connector protein (phtcp) gene in Anaplasma marginale. The mutant did not cause disease and exhibited attenuated growth in its natural host (cattle). We then assessed its ability to confer protection against wild-type A. marginale infection challenge. Additionally, we compared vaccine protection with the mutant to that of whole cell A. marginale inactivated antigens as a vaccine (WCAV) candidate. Upon infection challenge, non-vaccinated control cattle developed severe disease, with an average 57% drop in packed cell volume (PCV) between days 26-31 post infection, an 11% peak in erythrocytic infection, and apparent anisocytosis. Conversely, following challenge, all animals receiving the live mutant did not develop clinical signs or anemia, or erythrocyte infection. In contrast, the WCAV vaccinees developed similar disease as the non-vaccinees following A. marginale infection, though the peak erythrocyte infection reduced to 6% and the PCV dropped 43%. This is the first study describing targeted mutagenesis and its application in determining in vivo virulence and vaccine development for an Anaplasma species pathogen. This study will pave the way for similar research in related Anaplasma pathogens impacting multiple hosts.
Topics: Anaplasma; Anaplasma marginale; Anaplasmosis; Animals; Cattle; Cattle Diseases; Dogs; Humans; Mutagenesis; Vaccine Development; Virulence
PubMed: 35576225
DOI: 10.1371/journal.ppat.1010540 -
PloS One 2022Increased preoperative red cell distribution width (RDW) is associated with higher mortality following non-cardiac surgery in patients older than 65 years. Little is...
Increased preoperative red cell distribution width (RDW) is associated with higher mortality following non-cardiac surgery in patients older than 65 years. Little is known if this association holds for all adult emergency laparotomy patients and whether it affects 30-day or long-term mortality. Thus, we examined the relationship between increased RDW and postoperative mortality. Furthermore, we investigated the prognostic worth of anisocytosis and explored a possible association between increased RDW and frailty in this cohort. We conducted a retrospective, single centre National Emergency Laparotomy Audit (NELA) database study at St Mary's Hospital Imperial NHS Trust between January 2014 and April 2018. A total of 356 patients were included. Survival models were developed using Cox regression analysis, whereas RDW and frailty were analysed using multivariable logistic regression. Underlying model assumptions were checked, including discrimination and calibration. We internally validated our models using bootstrap resampling. There were 33 (9.3%) deaths within 30-days and 72 (20.2%) overall. Median RDW values for 30-day mortality were 13.8% (IQR 13.1%-15%) in survivors and 14.9% (IQR 13.7%-16.1%) in non-survivors, p = 0.007. Similarly, median RDW values were lower in overall survivors (13.7% (IQR 13%-14.7%) versus 14.9% (IQR 13.9%-15.9%) (p<0.001)). Mortality increased across quartiles of RDW, as did the proportion of frail patients. Anisocytosis was not associated with 30-day mortality but demonstrated a link with overall death rates. Increasing RDW was associated with a higher probability of frailty for 30-day (Odds ratio (OR) 4.3, 95% CI 1.22-14.43, (p = 0.01)) and overall mortality (OR 4.9, 95% CI 1.68-14.09, (p = 0.001)). We were able to show that preoperative anisocytosis is associated with greater long-term mortality after emergency laparotomy. Increasing RDW demonstrates a relationship with frailty. Given that RDW is readily available at no additional cost, future studies should prospectively validate the role of RDW in the NELA cohort nationally.
Topics: Adult; Cohort Studies; Erythrocyte Indices; Frailty; Humans; Prognosis; Retrospective Studies; Risk Factors
PubMed: 35511937
DOI: 10.1371/journal.pone.0266041 -
Kardiologia Polska 2022
The relationship between anisocytosis, quantitative and qualitative characteristics of coronary atherosclerosis, and major adverse cardiac events in patients with coronary artery disease: Rationale and study design.
Topics: Coronary Angiography; Coronary Artery Disease; Humans; Myocardial Infarction; Risk Factors
PubMed: 35475462
DOI: 10.33963/KP.a2022.0111 -
Medicina (Kaunas, Lithuania) Mar 2022Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron...
Anemia is common in multiple myeloma (MM) and is caused by a complex pathomechanism, including impaired iron homeostasis. Our aim is to evaluate the biomarkers of iron turnover: serum soluble transferrin receptor (sTfR) and hepcidin-25 in patients at various stages of MM in relation with markers of anemia, iron status, inflammation, renal impairment and burden of the disease and as predictors of mortality. Seventy-three MM patients (six with smoldering and 67 with symptomatic disease) were recruited and observed for up to 27 months. Control group included 21 healthy individuals. Serum sTfR and hepcidin were measured with immunoenzymatic assays. MM patients with and without anemia had higher sTFR compared to controls, while only anemic patients had higher hepcidin-25. Both hepcidin-25 and sTfR were higher in anemic than non-anemic patients. Higher hepcidin-25 (but not sTfR) was associated with increasing MM advancement (from smoldering to International Staging System stage III disease) and with poor response to MM treatment, which was accompanied by lower blood hemoglobin and increased anisocytosis. Neither serum hepcidin-25 nor sTfR were correlated with markers of renal impairment. Hepcidin-25 predicted blood hemoglobin in MM patients independently of other predictors, including markers of renal impairment, inflammation and MM burden. Moreover, both blood hemoglobin and serum hepcidin-25 were independently associated with patients' 2-year survival. Our results suggest that hepcidin-25 is involved in anemia in MM and its concentrations are not affected by kidney impairment. Moreover, serum hepcidin-25 may be an early predictor of survival in this disease, independent of hemoglobin concentration. It should be further evaluated whether including hepcidin improves the early diagnosis of anemia in MM.
Topics: Anemia; Hemoglobins; Hepcidins; Humans; Kidney Diseases; Multiple Myeloma; Receptors, Transferrin
PubMed: 35334593
DOI: 10.3390/medicina58030417 -
Heliyon Mar 2022Insecticides are commonly used pesticides in the world. Chronic exposure to insecticides has adverse effects on various human body organs. In this study, hematological...
Insecticides are commonly used pesticides in the world. Chronic exposure to insecticides has adverse effects on various human body organs. In this study, hematological findings were assessed in workers in an insecticide manufacturing plant. Hematological parameters and clinical symptoms were recorded in 99 workers exposed to insecticides and 107 workers not exposed to them in a cross-sectional study. Assessment of the hematological results showed a higher prevalence of thrombocytosis in the exposed group than the non-exposed group (P < 0.05). Mean white blood cell (WBC) and platelet counts, anisocytosis of red blood cells (RBCs), and neutrophils to lymphocytes ratio (NLR) were significantly higher in the exposed group compared to the non-exposed group (P < 0.05). Prevalence rates of headache, itchy skin, cough, and sleep disorders were higher in the exposed group than in the non-exposed group (P < 0.05). Chronic exposure to insecticides can alter hematological parameters in the normal range. Occupational exposure to insecticides may increase WBCs, platelet count, NLR, and red cell distribution width (RDW). It can also cause thrombocytosis. Complete blood count (CBC), as an inexpensive and accessible tool, can help monitor workers' health status exposed to insecticides properly.
PubMed: 35299610
DOI: 10.1016/j.heliyon.2022.e09040 -
Veterinary Medicine and Science May 2022Gross, histopathological, and immunohistochemical characteristics of uveal melanocytic neoplasms in dogs and cats were investigated.
OBJECTIVE
Gross, histopathological, and immunohistochemical characteristics of uveal melanocytic neoplasms in dogs and cats were investigated.
SAMPLES
Thirty-two enucleated globes with uveal melanocytic neoplasms, 27 from dogs and 5 from cats, were examined.
PROCEDURES
Morphological characteristics of uveal melanocytic neoplasms in dogs and cats were evaluated with anti-PNL2, anti-Melan-A, anti-Ki-67, anti-caspase-3, and anti-BAP1 immunomarkers. Statistical analysis was performed to compare canine melanocytomas and melanomas.
RESULTS
The 32 uveal neoplasms were classified as melanocytomas (19/27 in dogs) or melanomas (8/27 in dogs, 5/5 in cats). Most tumours (84%) were located in the anterior uvea. Neoplastic cells were classified as epithelioid, spindle-shaped, mixed, or special type (balloon and signet ring cells). The percentage of cells with melanin, melanin concentration within cells, anisocytosis and anisokaryosis, mitotic count, lymphocytic inflammation, necrosis, vascular invasion, and glaucoma were also characterized. Anisocytosis, percentage of neoplastic cells with melanin, mitotic count, and indices (proliferation and apoptotic) varied significantly between canine uveal melanomas and melanocytomas; in general, melanomas had greater cell variability, were less pigmented, and had a higher mitotic count. The melanocytic origin of the neoplasms was confirmed by positive anti-PNL2 immunolabelling (29/32) and positive anti-Melan-A immunolabelling (3/32). In canine uveal melanomas, anisocytosis and anisokaryosis correlated with less pigmentation and minimal pigmentation correlated with a high percentage of immunolabelling for caspase-3.
CONCLUSIONS
Uveal melanocytomas were more common in dogs, and uveal melanomas were more frequent in cats. Anisocytosis, percentage of neoplastic cells with melanin, and mitotic count are important histologic characteristics of malignancy to evaluate in uveal melanocytic neoplasms. The proliferation and apoptotic indices are relevant when comparing malignant tumours with benign tumours.
Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Melanins; Melanoma; Uvea
PubMed: 35122675
DOI: 10.1002/vms3.752 -
The Canadian Veterinary Journal = La... Feb 2022A 12-year-old, spayed female, Maltese dog with a round and firm mass on the dorsal part of the left rear paw and a cervical mass was brought to the clinic. The paw mass...
A 12-year-old, spayed female, Maltese dog with a round and firm mass on the dorsal part of the left rear paw and a cervical mass was brought to the clinic. The paw mass was contiguous to the adjacent tendon; it was composed of neoplastic mesenchymal cells and had scattered foci of calcification with chondroid differentiation microscopically. The neoplastic cells were positive for vimentin and S100, but negative for desmin and smooth muscle actin. Microscopic features and immunohistochemistry results were consistent with calcifying aponeurotic fibroma (CAF). The cervical mass was composed of polygonal cells forming acini with marked anisocytosis and anisokaryosis and diagnosed as thyroid follicular carcinoma. No recurrence or metastasis occurred during follow-up. To the best of our knowledge, this is the first case of canine CAF with features identical to its human counterparts. Key clinical message: This report describes the rare case of calcifying aponeurotic fibroma on the paw in a dog. This is apparently the first case in the veterinary literature with identical clinical and pathological features to the human counterpart.
Topics: Animals; Calcinosis; Dog Diseases; Dogs; Female; Fibroma; Fibroma, Ossifying; Soft Tissue Neoplasms
PubMed: 35110769
DOI: No ID Found -
Journal of Hematology Dec 2021The monthly continuous erythropoietin receptor activator (CERA) utilization maintains stable hemoglobin (Hb) after conversion from weekly epoetin-β (EB); however, how...
Monthly Continuous Erythropoietin Receptor Activator Versus Weekly Epoetin-Beta, Similar Hemoglobinization but Different Anisocytosis Degree in Hemodialysis Patients: A Randomized Controlled Trial.
BACKGROUND
The monthly continuous erythropoietin receptor activator (CERA) utilization maintains stable hemoglobin (Hb) after conversion from weekly epoetin-β (EB); however, how the different pharmacologic properties affect the red blood cell (RBC) size determined by RBC distribution width (RDW) has not been evaluated yet. We assess the potential differences in iron metabolism, plasma erythropoietin (EPO), hepcidin, and soluble α-Klotho (α-Klotho) levels as an emergent hematopoiesis factor.
METHODS
Thirty-seven chronic hemodialysis patients were included from January 2010 to November 2011 and randomized (1:1) to continue with EB or to convert to monthly CERA. Primary outcome was the mean change in Hb between groups at months 0, 3 and 6, and the percentage of patients who maintained stable Hb (Hb ± 1 g/dL from baseline level to month 6). Secondary outcomes were the influence on the erythropoietic process and iron metabolism markers. Thirty-one patients completed the study (CERA: n = 15, EB: n = 16).
RESULTS
The mean (95% confidence interval (CI)) Hb difference between groups was 0.28 g/dL (-0.36 to 0.93). There was no difference between the percentages of patients with stable Hb levels. In the CERA group RDW values increased progressively (interaction erythropoietin-stimulating agent (ESA) type and time on RDW values, F (1.57, 45.60) = 17.17, P < 0.01, partial η = 0.37) and the mean corpuscular volume changed at the different time points, (F (2, 28) = 29.12, P = 0.03, partial η = 0.23). During the evaluation period, in the CERA group, EPO was higher, and hepcidin and ferritin decreased significantly. α-Klotho decreased in both groups and correlated negatively with the changes on the RDW and positively with transferrin and serum iron. The number of serious adverse events was higher at the CERA group.
CONCLUSIONS
Monthly CERA maintained Hb concentrations; however, it showed a significant effect on RDW, probably due to its impact on the EPO and hepcidin levels. α-Klotho decreased significantly in both groups, and its changes correlated with the changes in iron metabolism. Whether the RDW evolution was associated with the serious adverse events (SAEs) is a feasible hypothesis that needs to be confirmed in large studies.
PubMed: 35059087
DOI: 10.14740/jh862