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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 -
Veterinary Clinical Pathology Dec 2022A 7-year-old mixed-breed neutered male cat was presented with a history of chronic vomiting with increased frequency in the last month, progressing to depression and...
A 7-year-old mixed-breed neutered male cat was presented with a history of chronic vomiting with increased frequency in the last month, progressing to depression and profuse projectile vomiting. Abdominal ultrasonography revealed an area of marked segmental duodenal thickening associated with a nodule, and euthanasia was performed due to a poor prognosis. Grossly, at the postmortem examination, the wall of a duodenal segment was severely expanded by a nodule measuring 5.0 cm in diameter, resulting in marked luminal narrowing and obstruction. Smears were made by scraping the cut surface of the tumor during the postmortem examination. The smears were highly cellular and contained mesenchymal cells arranged individually or in large non-cohesive aggregates. Cells varied in morphology from spindle to round to stellate-shaped with marked anisocytosis and anisokaryosis. Numerous bi- and multinucleated neoplastic cells were observed. Histologic examination revealed a densely cellular neoplastic proliferation of mesenchymal cells that effaced the duodenal submucosa, muscularis externa, and serosa layers. Most cells were spindle-shaped; however, some tumor areas had numerous round cells and bi- and multinucleated neoplastic cells. Spindle cells showed variable cytoplasmic immunoreactivity for vimentin, smooth muscle actin, and desmin. Round, bi-, and multinucleated giant cells only had marked multifocal cytoplasmic immunoreactivity for vimentin. Neoplastic cells did not have immunoreactivity for cytokeratin, GFAP, S100, and CD117. A final diagnosis of duodenal leiomyosarcoma was made. This article reports the pathologic, cytologic, and immunohistochemical findings of this case and discusses the main differential diagnoses in cases of intestinal sarcomas in domestic animals.
Topics: Cats; Male; Animals; Leiomyosarcoma; Vimentin; Sarcoma; Diagnosis, Differential; Vomiting; Cat Diseases
PubMed: 35466406
DOI: 10.1111/vcp.13124 -
Applied Biochemistry and Biotechnology Aug 2022The purpose of the paper is to study and analyse the annual dynamics of blood lipid parameters in highly qualified physical training. An experiment is a leading method...
The purpose of the paper is to study and analyse the annual dynamics of blood lipid parameters in highly qualified physical training. An experiment is a leading method for studying this problem that allows considering the problem comprehensively and in practice, as well as a comparison method, which makes it possible to analyse common features and differences as well as consider the dynamics of blood lipid parameters. Athletes who developed endurance or strength to a greater extent had no significant differences in many blood parameters. However, the groups of athletes who developed only strength had a more pronounced anisocytosis. In addition, it was possible to identify a correlation between the parameters of red blood cells and trained sports results. It was concluded that the highest indicators of the number of red blood cells, haemoglobin and average haemoglobin concentration in red blood cells were observed in strength training, and the lowest-in athletes training speed indicators. The article is of practical value for future research in the field of medicine and regenerative physiotherapy.
Topics: Athletes; Erythrocytes; Hemoglobins; Humans; Lipids; Physical Conditioning, Human; Sports
PubMed: 35451795
DOI: 10.1007/s12010-022-03918-4 -
Heart & Lung : the Journal of Critical... 2022Red Blood Cell Distribution Width (RDW), a measure of variability in size of circulating red blood cells and is a marker of inflammation.
BACKGROUND
Red Blood Cell Distribution Width (RDW), a measure of variability in size of circulating red blood cells and is a marker of inflammation.
OBJECTIVES
We sought to test the hypothesis that RDW reflects an inflammatory milieu permissive for cardiac fibrosis in those with Heart Failure and preserved ejection fraction (HFpEF).
METHODS
We analyzed the association between RDW and fibrosis in two separate cohorts. Cohort 1 (n = 200) was a retrospective analysis of blood biomarkers measured in the RELAX trial (Clinicaltrials.gov NCT00763867) and Cohort 2 (n = 160) included a single center cohort of patients with preserved ventricular function referred for cardiac magnetic resonance imaging (cMRI). Linear regression was used to adjust for potential confounders, and a mediation analysis used to explore relationships with exercise intolerance (peak VO2 max).
RESULTS
Within Cohort 1, anisocytosis (RDW > 14.5) was prevalent (49.5%) and was associated with greater baseline clinical comorbidities, a lower Peak VO2 and more frequent heart failure hospitalizations. The RDW was associated with biomarkers of inflammation and cardiac fibrosis. In Cohort 2, RDW was associated with cMRI myocardial fibrosis (extracellular volume; Spearman's rho=0.38, P<0.001) which was independent of age, sex, LV ejection fraction, and hematocrit (P = 0.026). Individuals with both anisocytosis and myocardial fibrosis identified a subgroup of at high risk for 2-year mortality (HR 16.28 [4.30-61.66], P<0.001).
CONCLUSIONS
In two independent cohorts of patients with HFpEF, elevated RDW is associated reduced exercise capacity and greater fibrosis as measured by serum biomarkers and cMRI. Additional studies are needed to validate this novel relationship.
Topics: Biomarkers; Exercise Tolerance; Fibrosis; Heart Failure; Humans; Inflammation; Retrospective Studies; Stroke Volume
PubMed: 35358904
DOI: 10.1016/j.hrtlng.2022.03.013 -
Legal Medicine (Tokyo, Japan) Jul 2022We analyzed 400 deaths that occurred in the bathtub during a 10-year period in the central area of Kanagawa prefecture in Japan. There were 72 (18%) medico-legal autopsy...
We analyzed 400 deaths that occurred in the bathtub during a 10-year period in the central area of Kanagawa prefecture in Japan. There were 72 (18%) medico-legal autopsy cases. The average age at death was 76.4 ± 11.9 years. Drowning (n = 21, 70.8%) was the most common cause of death in the 72 autopsy cases. The study examined the bodies of 40 cases within a postmortem interval of 3 days. The mean age of the 40 cases of sudden death during bathing was 68.6 ± 12.5 years. Results revealed cardiac hypertrophy in 12 cases (30%), lipofuscin deposition in 39 cases (97.5%), basophilic degeneration in 12 cases (30%), anisocytosis of the nucleus of myocardial cells in 18 cases (45%), perivascular fibrosis in 17 cases (42.5%), amyloid deposits in 1 case, and aortic valve calcification in 1 case. The hearts of control subjects who had lived to 20-99 years were also examined; the frequency of each change was higher in people older than 70 years. There was no statistically significant difference in age-related cardio-pathological changes between cases of sudden death during bathing in people in their 70s and controls in their 70s. It can be concluded that this age-related histopathological index is not related to sudden death during bathing. A large number of elderly people, including those without heart disease, have died during bathing. Preventive measures against sudden death during bathing are strongly recommended, e.g., elderly people should not be left totally unsupervised while they bathe.
Topics: Aged; Aged, 80 and over; Autopsy; Baths; Cause of Death; Death, Sudden; Death, Sudden, Cardiac; Drowning; Humans; Japan; Middle Aged
PubMed: 35344880
DOI: 10.1016/j.legalmed.2022.102057 -
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