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Pathogens & Immunity 2021Hepatitis-C virus (HCV) chronic infection can lead to cirrhosis, hepatocellular carcinoma (HCC), end-stage liver disease, cardiovascular disease (CVD), and mortality....
BACKGROUND
Hepatitis-C virus (HCV) chronic infection can lead to cirrhosis, hepatocellular carcinoma (HCC), end-stage liver disease, cardiovascular disease (CVD), and mortality. Transient Elastography (TE) is used to non-invasively assess fibrosis. Whether immune monitoring provides additive prognostic value is not established. Increased red-cell distribution width (RDW) and decreased absolute lymphocyte count (ALC) predict mortality in those without liver disease. Whether these relationships remain during HCV infection is unknown.
MATERIALS AND METHODS
A retrospective cohort of 1,715 single-site VA Liver Clinic patients receiving Transient Elastography (TE) 2014-2019 to evaluate HCV-associated liver damage were evaluated for RDW and ALC in relation to traditional parameters of cardiovascular risk, liver health, development of HCC, and mortality.
RESULTS
The cohort was 97% male, 55% African American, 26% with diabetes mellitus, 67% with hypertension, and 66% with tobacco use. After TE, 3% were subsequently diagnosed with HCC, and 12% (n=208) died. Most deaths (n=189) were due to non-liver causes. The TE score associated with prevalent CVD, positively correlated with atherosclerotic cardiovascular disease (ASCVD) 10-Year Risk Score, age, RDW, and negatively correlated with ALC. Patients with anisocytosis (RDW above 14%) or lymphopenia (ALC level under 1.2×10/L) had greater subsequent all-cause mortality, even after adjusting for age, TE score, and comorbidities. TE score, and to a modest degree RDW, were associated with subsequent liver-associated mortality, while TE score, RDW, and ALC were each independently associated with non-liver cause of death.
CONCLUSION
Widely available mortality calculators generally require multiple pieces of clinical information. RDW and ALC, parameters collected on a single laboratory test that is commonly performed, prior to HCV therapy may be pragmatic markers of long-term risk of mortality.
PubMed: 34988340
DOI: 10.20411/pai.v6i2.467 -
Biomarkers in Medicine Jan 2022Viral diseases remain a significant global health threat, and therefore prioritization of limited healthcare resources is required to effectively manage dangerous viral... (Review)
Review
Viral diseases remain a significant global health threat, and therefore prioritization of limited healthcare resources is required to effectively manage dangerous viral disease outbreaks. In a pandemic of a newly emerged virus that is yet to be well understood, a noninvasive host-derived prognostic biomarker is invaluable for risk prediction. Red blood cell distribution width (RDW), an index of red blood cell size disorder (anisocytosis), is a potential predictive biomarker for severity of many diseases. In view of the need to prioritize resources during response to outbreaks, this review highlights the prospects and challenges of RDW as a prognostic biomarker for viral infections, with a focus on hepatitis and COVID-19, and provides an outlook to improve the prognostic performance of RDW for risk prediction in viral diseases.
Topics: Animals; Biomarkers; COVID-19; Erythrocyte Indices; Erythrocytes; Hepatitis; Humans; Prognosis; Virus Diseases
PubMed: 34784758
DOI: 10.2217/bmm-2021-0364 -
Animals : An Open Access Journal From... Sep 2021Several extra-intestinal manifestations, including immune-mediated cytopenias, are reported in human inflammatory bowel disease (IBD), whereas they are poorly documented...
Several extra-intestinal manifestations, including immune-mediated cytopenias, are reported in human inflammatory bowel disease (IBD), whereas they are poorly documented in dogs. Hypothesizing that immune-mediated subclinical anemia can occur in canine IBD, the study aim was to evaluate the erythrogram and the presence of anti-RBC antibodies in dogs with IBD. IBD was diagnosed according to the following criteria: chronic gastrointestinal signs, ruling out of extra-intestinal diseases, no improvement with diet trial, histological evidence of inflammatory infiltration, and improvement after immunosuppressant therapy. Canine Chronic Enteropathy Clinical Activity Index (CCECAI) endoscopic and histopathological scores were assessed for each dog. Twenty-five dogs were enrolled, and each dog had a CBC evaluation prior to endoscopy. The CBC was performed using laser hematology analyzer and blood smears were carefully reviewed for the presence of nucleated RBC, anisocytosis, polychromasia, and Howell-Jolly bodies. IgG and IgM anti-RBC antibodies were evaluated with flow cytometry. A high frequency of positive cases for anti-RBC antibodies in dogs with IBD (17/25 dogs) was ascertained. Approximatively 50% of dogs showed some hematologic features of RBC regeneration in addition to hematologic findings consistent with chronic inflammation. Anti-RBC antibodies and signs of erythroid regeneration may suggest possible subclinical chronic immune-mediated hemolysis that can cause anemia in dogs with IBD, together with the chronic inflammation.
PubMed: 34573547
DOI: 10.3390/ani11092580 -
Blood Advances Dec 2021β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet...
β1-Tubulin plays a major role in proplatelet formation and platelet shape maintenance, and pathogenic variants in TUBB1 lead to thrombocytopenia and platelet anisocytosis (TUBB1-RT). To date, the reported number of pedigrees with TUBB1-RT and of rare TUBB1 variants with experimental demonstration of pathogenicity is limited. Here, we report 9 unrelated families presenting with thrombocytopenia carrying 6 β1-tubulin variants, p.Cys12LeufsTer12, p.Thr107Pro, p.Gln423*, p.Arg359Trp, p.Gly109Glu, and p.Gly269Asp, the last of which novel. Segregation studies showed incomplete penetrance of these variants for platelet traits. Indeed, most carriers showed macrothrombocytopenia, some only increased platelet size, and a minority had no abnormalities. Moreover, only homozygous carriers of the p.Gly109Glu variant displayed macrothrombocytopenia, highlighting the importance of allele burden in the phenotypic expression of TUBB1-RT. The p.Arg359Trp, p.Gly269Asp, and p.Gly109Glu variants deranged β1-tubulin incorporation into the microtubular marginal ring in platelets but had a negligible effect on platelet activation, secretion, or spreading, suggesting that β1-tubulin is dispensable for these processes. Transfection of TUBB1 missense variants in CHO cells altered β1-tubulin incorporation into the microtubular network. In addition, TUBB1 variants markedly impaired proplatelet formation from peripheral blood CD34+ cell-derived megakaryocytes. Our study, using in vitro modeling, molecular characterization, and clinical investigations provides a deeper insight into the pathogenicity of rare TUBB1 variants. These novel data expand the genetic spectrum of TUBB1-RT and highlight a remarkable heterogeneity in its clinical presentation, indicating that allelic burden or combination with other genetic or environmental factors modulate the phenotypic impact of rare TUBB1 variants.
Topics: Blood Platelets; Humans; Megakaryocytes; Thrombocytopenia; Tubulin
PubMed: 34516618
DOI: 10.1182/bloodadvances.2020004057 -
The Journal of Pediatrics Dec 2021To create neonatal reference intervals for the MicroR and HYPO-He complete blood count (CBC) parameters and to test whether these parameters are sensitive early markers...
Neonatal Reference Intervals for the Complete Blood Count Parameters MicroR and HYPO-He: Sensitivity Beyond the Red Cell Indices for Identifying Microcytic and Hypochromic Disorders.
OBJECTIVE
To create neonatal reference intervals for the MicroR and HYPO-He complete blood count (CBC) parameters and to test whether these parameters are sensitive early markers of disease at early stages of microcytic/hypochromic disorders while the CBC indices are still normal.
STUDY DESIGN
We retrospectively collected the CBC parameters MicroR and HYPO-He, along with the standard CBC parameters, from infants aged 0-90 days at Intermountain Healthcare hospitals using Sysmex hematology analyzers. We created reference intervals for these parameters by excluding values from neonates with proven microcytic disorders (ie, iron deficiency or alpha thalassemia) from the dataset.
RESULT
From >11 000 CBCs analyzed, we created reference intervals for MicroR and HYPO-He in neonates aged 0-90 days. The upper intervals are considerably higher in neonates than in adults, validating increased anisocytosis and polychromasia among neonates. Overall, 52% of neonates with iron deficiency (defined by reticulocyte hemoglobin equivalent <25 pg) had a MicroR >90% upper interval (relative risk, 4.14; 95% CI, 3.80-4.53; P < .001), and 68% had an HYPO-He >90% upper interval (relative risk, 6.64; 95% CI, 6.03-7.32; P < .001). These 2 new parameters were more sensitive than the red blood cell (RBC) indices (P < .001) in identifying 24 neonates with iron deficiency at birth.
CONCLUSIONS
We created neonatal reference intervals for MicroR and HYPO-He. Although Sysmex currently designates these as research use only in the US, they can be measured as part of a neonate's CBC with no additional phlebotomy volume or run time and can identify microcytic and hypochromic disorders even when the RBC indices are normal.
Topics: Anemia, Iron-Deficiency; Biomarkers; Humans; Infant; Infant, Newborn; Reference Values; Reticulocyte Count; Reticulocytes; Retrospective Studies
PubMed: 34389321
DOI: 10.1016/j.jpeds.2021.08.002 -
Laboratory Animals Dec 2021A 14-month-old male Armenian hamster () presented with a spontaneous, subcutaneous, firm mass (4.0 × 2.0 × 1.5 cm) on the ventral neck extending towards the...
A 14-month-old male Armenian hamster () presented with a spontaneous, subcutaneous, firm mass (4.0 × 2.0 × 1.5 cm) on the ventral neck extending towards the cheek pouch causing multifocal small oral ulcerations. This animal was immunized subcutaneously on the dorsal neck for the development of monoclonal antibodies seven months before presentation. The animal was euthanized and necropsy was performed. Histopathology of the mass showed a well demarcated, multilobulated, unencapsulated, highly cellular, neoplastic mass composed of spindle cells arranged in interlacing streams and bundles, with a moderate amount of fibrovascular stroma. The neoplastic cells exhibited indistinct cell borders and a moderate to large amount of eosinophilic, fibrillar cytoplasm, marked anisocytosis and anisokaryosis, binucleated and multinucleated cells, and high mitotic rate. Based on the histomorphologic features of the mass, and the presence of renal tubular hyaline globules and myeloid hyperplasia in the bone marrow, a diagnosis of histiocytic sarcoma was made. The presumptive diagnosis was confirmed by immunohistochemistry, upon which the neoplastic cells showed strong immunoreactivity for the histiocytic cell markers Iba1 and CD11b. Histiocytic sarcomas have been reported in Syrian () and Siberian dwarf () hamsters but, to our knowledge, the current report represents the first case of histiocytic sarcoma described in an Armenian hamster. It is plausible to consider the animal's experimental immunization history and the development of the histiocytic sarcoma to be related. An association between adjuvanted vaccines and soft-tissue sarcomas has been described in cats and referred to as feline injection-site sarcomas.
Topics: Animals; Antibodies, Monoclonal; Cats; Cricetinae; Cricetulus; Histiocytic Sarcoma; Immunohistochemistry; Male; Mesocricetus
PubMed: 34353145
DOI: 10.1177/00236772211033672 -
BMC Veterinary Research Jul 2021Serious disease outbreaks in cattle are usually associated with blood pathogens. This study aims to detect blood pathogens namely Theileria species, Anaplasma species,...
Molecular detection of Theileria species, Anaplasma species, Candidatus Mycoplasma haemobos, Trypanosoma evansi and first evidence of Theileria sinensis-associated bovine anaemia in crossbred Kedah-Kelantan x Brahman cattle.
BACKGROUND
Serious disease outbreaks in cattle are usually associated with blood pathogens. This study aims to detect blood pathogens namely Theileria species, Anaplasma species, Candidatus Mycoplasma haemobos and Trypanosoma evansi, and determine their phylogenetic relationships and haemato-biochemical abnormalities in naturally infected cattle.
METHODS
Molecular analysis was achieved by PCR amplification and sequencing of PCR amplicons of 18SrRNA gene of Theileria species, 16SrRNA genes of Anaplasma and Mycoplasma species, MPSP genes of T. orientalis and T. sinensis, MSP4 gene of A. marginale, 16SrRNA gene of Candidatus Mycoplasma haemobos, and RoTat1.2 VSG gene of Trypanosoma evansi, in sixty-one (61) clinically ill Kedah-Kelantan x Brahman cattle in Pahang, Malaysia.
RESULTS
A total of 44 (72.13%) cattle were infected with more than one blood pathogen. Theileria species was the blood pathogen with the highest molecular detection rate (72.13, 95% CI 59.83-81.81%). Nucleotide blast analyses of all sequences demonstrated high degree of molecular similarity (98-100%) in comparison with their respective reference sequences. Analysis of 18SrRNA gene sequences of Theileria species and 16SrRNA gene sequences of Anaplasma species revealed Theileria sinensis and Anaplasma platys respectively as additional species detected in these cattle. MPSP-PCR analysis was conducted for further confirmation of T. sinensis. The blood picture of eight infected cattle groups revealed poikilocytosis, anisocytosis, rouleaux formation and degenerative left shift. High mean erythrocyte fragility values were common in infected cattle groups. Anaemia of the macrocytic normochromic type and spherocytes were observed in the T. evansi and Anaplasma platys + Theileria sinensis double species co-infected cattle group. Normocytic normochromic anaemia was observed in the T. sinensis infected cattle group. Significant (p < 0.05) increases in serum liver and kidney parameters, total protein, globulin, total and unconjugated bilirubin and decreased albumin values were observed in the T. evansi infected cattle when compared to clinically healthy cattle.
CONCLUSION
We present the first evidence of Theileria sinensis-associated bovine anaemia (TSABA) in Malaysian cattle. Because of the high occurrence of bovine theileriosis and detection of A. platys, there is an urgent need for appropriate preventive and control measures against these blood pathogens.
Topics: Anaplasma; Anaplasmosis; Anemia; Animals; Cattle; Cattle Diseases; Female; Malaysia; Male; Mycoplasma; Mycoplasma Infections; Theileria; Theileriasis; Trypanosoma; Trypanosomiasis
PubMed: 34275459
DOI: 10.1186/s12917-021-02902-0 -
Veterinary Sciences Jun 2021Anemia is considered a common finding in dogs with chronic kidney disease (CKD), typically as normochromic, normocytic, and non-regenerative. Although anemia can occur...
Anemia is considered a common finding in dogs with chronic kidney disease (CKD), typically as normochromic, normocytic, and non-regenerative. Although anemia can occur at any CKD IRIS (International Renal Interest Society) stage, its severity is related with the loss of kidney function. The aim of the present study was to retrospectively evaluate quantitative and morphological abnormalities of the erythrogram in dogs at different CKD IRIS stages. A total of 482 CBCs from 3648 initially screened were included in the study. Anemia was present in 302/482 (63%) dogs, in the majority of which it was normochromic, normocytic, and non-regenerative (295/302; 98%). The number of reticulocytes was <60,000/μL in the majority of dogs (248/295; 84%), with a correlation between poor regeneration rate and progression of CKD ( = 0.0001). The frequency of anemia significantly differed ( = 0.0001) among the IRIS stages: 108/231 (47%) in IRIS 2, 77/109 (71%) in IRIS 3, and 117/142 (82%) in IRIS 4. Dogs at IRIS stages 3 and 4 were more likely to have moderate to severe anemia, compared to dogs at IRIS stage 2 ( = 0.0001). Anisocytosis was the most frequent morphological abnormality (291/482; 60%), whereas the presence of poikilocytosis showed an association with progression of IRIS stages ( = 0.009). Among different morphological abnormalities, the frequency of fragmented red blood cells and Howell-Jolly bodies showed a significant association with the progression of CKD. Anemia was a frequent finding in CKD dogs, mostly associated with none to poor regeneration rate. Similar to human medicine, advanced CKD stages are more frequently characterized by morphological alterations, such as fragmented red blood cells and Howell-Jolly bodies, which may suggest a more severe condition of reduced bone marrow activity and microangiopathy.
PubMed: 34209294
DOI: 10.3390/vetsci8070123 -
Animals : An Open Access Journal From... Jun 2021Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the...
Apocrine gland anal sac adenocarcinoma (AGASACA) is locally aggressive and highly metastatic to regional lymph nodes. The aim of this study was to evaluate the prognostic significance of Ki67 in surgically excised AGASACA. Prognostic impact of size, regional lymph nodes metastasis, hypercalcemia, histologic pattern, mitotic count, necrosis, inflammatory and lympho-vascular invasion, anisokaryosis and anisocytosis was also evaluated. Thirty-five dogs were included, twenty-four of which also had metastatic lymph nodes. When the entire population was evaluated, only metastatic disease spread to regional lymph nodes, and necrosis and inflammatory infiltration were correlated to prognosis. When only dogs with metastatic disease were evaluated, size, solid histologic pattern, presence of lymphatic and vascular invasion showed influence on prognosis. Ki67 index was not associated with survival time and disease free interval in any case. The results of this study showed that lymph nodes metastasis at diagnosis reduced disease free interval. Moreover, tumor size greater than 5.25 cm, presence of lymphatic and vascular invasion and a solid histologic pattern were associated with a shorter survival time in dogs with metastasis to regional lymph nodes. Ki67 expression was not significantly associated with prognosis, therefore it could not be considered as a prognostic factor in this tumor type, while the role of hypercalcemia remained unclear.
PubMed: 34199347
DOI: 10.3390/ani11061649 -
BMC Anesthesiology Jun 2021Megaloblastic anemia or bone marrow changes could occur after prolonged nitrous oxide inhalation via vitamin B inactivation related DNA synthesis impairment. Previous...
BACKGROUND
Megaloblastic anemia or bone marrow changes could occur after prolonged nitrous oxide inhalation via vitamin B inactivation related DNA synthesis impairment. Previous researches have studied hematological changes with nitrous oxide exposure, but only in adults or adolescents. Pre-school age children with active hematopoietic red bone marrow are more vulnerable to potential side effects of nitrous oxide and might experience growth impairment. The purpose of our study was to analyze red blood cell morphology changes under nitrous oxide anesthesia in pre-school age children.
METHODS
One hundred thirty-six children under 5 years old scheduled for hemivertebra resection were analyzed. According to fresh gas type in anesthesia records, 71 children who received nitrous oxide in oxygen during anesthesia maintenance were categorized into the nitrous oxide group and the other 65 who received air in oxygen were the air group. Complete blood counts in perioperative period were assessed for anemia, macrocytosis, microcytosis, anisocytosis, hyperchromatosis and hypochromatosis. The peak value and change percentage were calculated for mean corpuscular volume and red cell distribution width.
RESULTS
Forty-two children in the air group (64.6%) and 30 in the nitrous oxide group (42.3%) developed anemia (P = 0.009). None developed macrocytosis in both groups. Postoperative mean corpuscular volume peaked (mean [95% confidence interval]) at 83.7(82.9-84.4) fL, and 83.2(82.4-83.9) fL and postoperative red cell distribution width at 13.8% (13.4-14.2%), and 13.9% (13.6-14.2%) for the air group and the nitrous oxide group. Both the relative change of mean corpuscular volume (P = 0.810) and red cell distribution width (P = 0.456) were similar between the two groups.
CONCLUSIONS
No megaloblastic red blood cell changes were observed with nitrous oxide exposure for 4 h in pre-school age children undergoing hemivertebra resection.
Topics: Anesthetics, Inhalation; Blood Cell Count; Child, Preschool; Cohort Studies; Erythrocyte Indices; Erythrocytes; Female; Humans; Male; Nitrous Oxide; Retrospective Studies; Scoliosis
PubMed: 34134658
DOI: 10.1186/s12871-021-01388-5