-
Respirology (Carlton, Vic.) Oct 2016Limited data exist regarding factors predicting respiratory failure (RF) in non-immunocompromised patients with adenovirus (AdV) pneumonia.
BACKGROUND AND OBJECTIVE
Limited data exist regarding factors predicting respiratory failure (RF) in non-immunocompromised patients with adenovirus (AdV) pneumonia.
METHODS
We described characteristics of AdV pneumonia (n = 91) versus non-AdV pneumonia (n = 55) and compared clinico-laboratory and radiological characteristics in patient groups categorized by RF.
RESULTS
All 91 AdV pneumonia patients presented with acute respiratory symptoms and radiological infiltrations and had significantly lower levels of white blood cell counts and platelet counts compared with non-AdV pneumonia. Of them, 67 patients had mild pneumonia without RF (non-RF), 14 patients had no RF at admission but progressed to RF during hospitalization (progressed to RF) and 10 patients had RF at admission (initial RF). Initial monocyte percentage and absolute monocyte counts in RF patient groups (progressed to RF and initial RF) were significantly lower than those of non-RF patients (both P < 0.001), and the differences among progressed to RF and initial RF patients were not significant. Chest computed tomography findings such as dominant pattern or distribution, clinical symptoms, and bacterial or viral co-infections other than AdV were not discriminable between patients who had RF and those who did not. On univariate analysis, initial monocytopenia, multilobar infiltrations and pleural effusion were associated with RF. However, on multivariable analysis, only initial monocytopenia remained significant (P = 0.004) for predicting RF.
CONCLUSION
Our data suggest that initial monocytopenia may help to predict RF during the course of AdV pneumonia in non-immunocompromised patients.
Topics: Adenoviridae; Coinfection; Female; Hospitalization; Humans; Influenza, Human; Male; Pneumonia, Viral; Respiratory Insufficiency; Retrospective Studies; Young Adult
PubMed: 27301912
DOI: 10.1111/resp.12828 -
Frontiers in Immunology 2022The transcription factor GATA2 plays a key role in the survival and self-renewal of hematopoietic stem and progenitor cells. Autosomal dominant variants in cause a...
The transcription factor GATA2 plays a key role in the survival and self-renewal of hematopoietic stem and progenitor cells. Autosomal dominant variants in cause a broad spectrum of heterogeneous phenotypes. Here, we present our experience with GATA2 deficiency in a retrospective multicenter analysis of computerized medical records of adult patients (age ≥18 years) treated between 2018 and 2022 at Shaare Zedek Medical Center in Jerusalem and Sheba Tel-Hashomer Medical Center in Ramat Gan, Israel. Two male and two female patients with GATA2 deficiency were identified. Three of the patients presented with symptoms in adult life and all patients were diagnosed as adults. Age at presentation was 10.5-36 years and age at diagnosis 24-47 years. Diagnosis was delayed in all patients by 1-24.5 years. The phenotypic diversity was notable. Patients presented with myelodysplastic syndrome (n=2), pulmonary alveolar proteinosis (n=1), and recurrent viral (n=1), bacterial (n=3), and mycobacterial (n=1) infections. Bone marrow biopsy revealed cytogenetic abnormalities in one patient (monosomy 7). Patients were diagnosed by exome sequencing (n=3) and Sanger sequencing of the coding exons in (n=1). Novel heterozygous variants (c.177C>A, p.Y59* and c.610dup, p.R204Pfs*78) were identified in two patients. Immune workup revealed B cell lymphopenia and monocytopenia in all tested patients. One patient died from overwhelming sepsis despite all patients being treated with antibiotics and anti-mycobacterials. Our cohort highlights the phenotypic diversity, late presentation, and delayed diagnosis of GATA2 deficiency. Increased awareness of this primary immune deficiency presenting in adult life is needed and should involve a high index of suspicion.
Topics: Bone Marrow; Delayed Diagnosis; Female; GATA2 Deficiency; GATA2 Transcription Factor; Humans; Male; Myelodysplastic Syndromes; Phenotype
PubMed: 35603181
DOI: 10.3389/fimmu.2022.886117 -
Cancer Immunology, Immunotherapy : CII 1997The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in... (Review)
Review
The class I IgG receptor (Fc gamma RI or CD64 receptor), which is present on key cytotoxic effector cells, has been shown to initiate the destruction of tumor cells in vitro and has been hypothesized to play a role in the destruction of antibody-coated cells such as platelets in idiopathic thrombocytopenia purpura (ITP). This overview summarizes the clinical experience with CD64-directed immunotherapy in cancer patients with the bispecific antibodies MDX-447 [humanized Fab anti-CD64 x humanized Fab anti-(epidermal growth factor receptor, EGFR)] and MDX-H210 (humanized Fab anti-DC64 x Fab anti-HER2/neu), and with the anti-CD64 monoclonal antibody (mAB) MDX-33 (H22) in the modulation of monocyte CD64 in vivo. In an ongoing phase I/II open-label trial with progressive dose escalation (1-15 mg/m2), patients with treatment refractory EGFR-positive cancers (renal cell carcinoma (RCC), head and neck, bladder, ovarian, prostate cancer and skin cancer) are treated weekly with intravenous MDX-447, with and without granulocyte-colony-stimulating factor (G-CSF). MDX-447 has been found to be immunologically active at all doses, binding to circulating monocytes and neutrophils (when given with G-CSF), causing monocytopenia and stimulating increases in circulating plasma cytokines. MDX-447 is well tolerated, the primary toxicities being fever, chills, blood pressure lability, and pain/ myalgias. Of 36 patients evaluable for response, 9 have experienced stable disease of 3-6 month's duration. The optimal dose and the maximal tolerated dose (MTD) have yet to be defined; dose escalation continues to define better the dose, toxicity, and the potential therapeutic role of this bispecific antibody. Three MDX-H210 phase II trials are currently in progress, all using the intravenous dose of 15 mg/m2 given with granulocyte/macrophage (GM-CSF). These consist of one trial each in the treatment of RCC patients, patients with prostate cancer, and colorectal cancer patients, all of whom have failed standard therapy. At the time of writing, 11 patients have been treated in these phase II trials. Four patients have demonstrated antitumor effects. Patients demonstrating responses include 2 with RCC and 2 with prostate cancer. One RCC patient has had a 54% reduction in size of a hepatic metastatic lesion and the other has had a 49% decrease in the size of a lung metastasis with simultaneous clearing of other non-measurable lung lesions. Regarding the two patients with prostate cancer, one has had a 90% reduction in serum prostate-specific antigen (PSA; 118-11 ng/ml), which has persisted for several months; the other patient with prostate has had a 70% reduction of serum PSA (872 ng/ml to 208 ng/ml) within the first month of treatment. Both patients have also demonstrated symptomatic improvement. In a completed phase I and in ongoing phase I/II clinical trials, patients with treatment-refractory HER2/neu positive cancers (breast, ovarian, colorectal, prostate) have been treated with MDX-H210, which has been given alone and in conjunction with G-CSF, GM-CSF, and interferon gamma (IFN gamma). These trials have been open-label, progressive dose-escalation (0.35-135 mg/m2) studies in which single, and more often, multiple weekly doses have been administered. MDX-H210 has been well tolerated, with untoward effects being primarily mild-to-moderate flu-like symptoms. The MTD has not yet been defined. MDX-H210 is immunologically active, binding to circulating monocytes, causing monocytopenia, as well as stimulating increases in plasma cytokine levels. Furthermore, some patients have evidence of active antitumor immunity following treatment with MDX-210. Antitumor effects have been seen in response to MDX-H210 administration; these include 1 partial, 2 minor, and 1 mixed tumor response; 15 protocol-defined stable disease responses have occurred. (ABSTRACT TRUNCATED)
Topics: Antibodies, Bispecific; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; ErbB Receptors; Humans; Neoplasms; Purpura, Thrombocytopenic, Idiopathic; Receptor, ErbB-2; Receptors, IgG
PubMed: 9435876
DOI: 10.1007/s002620050435 -
American Journal of Blood Research 2020Aplastic anemia (AA) is a type of anemia that is caused by an intrinsic defect of hematopoietic progenitors or an extrinsic immune mediated destruction of stem cells....
Aplastic anemia (AA) is a type of anemia that is caused by an intrinsic defect of hematopoietic progenitors or an extrinsic immune mediated destruction of stem cells. Patients commonly presented with pancytopenia, particularly leukopenia that renders patient susceptible to various infections. COVID-19 is one of these infections that could be life threatening and highly contagious. Infection with COVID-19 is expected in a patient who developed fever, respiratory manifestations, leukopenia and lymphopenia together with history suggestive of exposure to infection. Furthermore COVID-19 was found associated with thrombocytopenia, agranulocytosis and monocytopenia in severe cases. Thus the relationship between COVID-19 infection and AA would be a vicious circle as both cause leukopenia and lymphopenia. This study aimed to break this circle, through proposing risk stratification of vulnerability to COVID-19 in AA patients who were admitted in our institution in the period from Mar. 2018 to Mar. 2020 followed by a strict preventive plan tailored for each risk group. 79% of AA patients were at high risk of acquiring COVID-19 infection if exposed. This group of patients have to be targeted with more aggressive preventive plan than normal healthy persons. In conclusion this study proposed next step in combating COVID-19 infection through mass survey of high risk people then application of specific precautions to them, perhaps they could be candidate for future vaccine or prophylactic treatment.
PubMed: 32923084
DOI: No ID Found -
Journal of Family Medicine and Primary... Aug 2022COVID-19 has become a major health concern since 2020. Its clinical presentation varies from asymptomatic cases to cases with respiratory failure needing ICU management....
BACKGROUND AND OBJECTIVE
COVID-19 has become a major health concern since 2020. Its clinical presentation varies from asymptomatic cases to cases with respiratory failure needing ICU management. It has created a huge burden on limited health care resources. We need better understanding of the pathogenesis and interplay between virus and other factors which decide outcome. We seek biomarkers to predict severe illness to offer better triaging of patients to provide hospital-based care to the patients at risk of severe illness.
MATERIAL AND METHODS
We took 801 consecutive RT-PCR-positive COVID cases coming to our center. Their hematological work-up, such as complete blood count, peripheral smear, reticulocyte count, and G6PD activity, was tested. The pattern of hematological abnormalities was assessed across disease severity groups to identify predictors of severe illness from basic investigation. Also, the interplay between iron deficiency and possible hemoglobinopathy trait and COVID was explored.
RESULTS DISCUSSION AND CONCLUSION
We found old age, male gender, diabetes, neutrophilia, lymphopenia, monocytopenia, and eosinopenia at presentation to be associated with moderate to severe illness and may help in triaging with other inflammatory and radiological parameters. We found thrombocytosis rather than thrombocytopenia as a predictor of severe illness. Our preliminary findings suggest the need to explore the protective role of hemoglobinopathy traits and iron deficiency against severe COVID illness.
PubMed: 36353011
DOI: 10.4103/jfmpc.jfmpc_44_22 -
PloS One 2021A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analysing clinical presentation on admission and the... (Observational Study)
Observational Study
INTRODUCTION
A new respiratory virus, SARS-CoV-2, has emerged and spread worldwide since late 2019. This study aims at analysing clinical presentation on admission and the determinants associated with admission in intensive care units (ICUs) in hospitalized COVID-19 patients.
PATIENTS AND METHODS
In this prospective hospital-based study, socio-demographic, clinical and biological characteristics, on admission, of adult COVID-19 hospitalized patients presenting from the community for their first admission were prospectively collected and analysed. Characteristics of patients hospitalized in medical ward to those admitted in ICU were compared using Mann-Whitney and Chi-square or Fisher exact test when appropriate. Univariate logistic regression was first used to identify variables on admission that were associated with the outcome i.e. admission to an ICU versus total hospital stay in a medical ward. Forward selection was then applied beginning with sex, age and temperature in the multivariable logistic regression model.
RESULTS
Of the 412 patients included, 325 were discharged and 87 died in hospital. Multivariable regression showed increasing odds of ICU hospitalization with temperature (OR, 1.56 [95% CI, 1.06-2.28] per degree Celsius increase), oxygen saturation <90% (OR, 12.45 [95% CI, 5.27-29.4]), abnormal lung auscultation on admission (OR, 3.58 [95% CI, 1.58-8.11]), elevated level of CRP (OR, 2.7 [95% CI, 1.29-5.66for CRP>100mg/L vs CRP<10mg/L). and monocytopenia (OR, 3.28 [95% CI, 1.4-7.68]) were also associated with increasing odds of ICU hospitalization. Older patients were less likely to be hospitalized in ICU (OR, 0.17 [95%CI, 0.05-0.51].
CONCLUSIONS
Age and delay between onset of symptoms and hospital admission were associated with the risk of hospitalisation in ICU. Age being a fixed variable, interventions that shorten this delay would improve the prognosis of Covid-19 patients.
Topics: Adult; Aged; Aged, 80 and over; COVID-19; Female; France; Hospital Mortality; Hospitalization; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Prognosis; Prospective Studies; SARS-CoV-2
PubMed: 33503018
DOI: 10.1371/journal.pone.0243709 -
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 -
Journal of Fungi (Basel, Switzerland) Apr 2022The cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared...
The cultural recovery of Mucorales from hyphae-laden tissue is poor, and the clinical implications of culture positivity are scarcely studied. Therefore, we compared clinical and histopathological characteristics of culture-positive and culture-negative histology-proven pulmonary mucormycosis cases among cancer patients. Histology specimens were blindly reviewed by a thoracic pathologist and graded on four histopathologic features: hyphal quantity, tissue necrosis, tissue invasion, and vascular invasion. Twenty cases with a corresponding fungal culture were identified; five were culture-positive, and fifteen were culture-negative. Although no statistically significant differences were found, culture-positive patients were more likely to exhibit a high burden of necrosis and have a high burden of hyphae but tended to have less vascular invasion than culture-negative patients. In terms of clinical characteristics, culture-positive patients were more likely to have acute myeloid leukemia (60% vs. 27%, = 0.19), a history of hematopoietic cell transplant (80% vs. 53%, = 0.31), severe lymphopenia (absolute lymphocyte count ≤ 500/µL, 100% vs. 73%, = 0.36), and monocytopenia (absolute monocyte count ≤100/µL, 60% vs. 20%, = 0.11). Forty-two-day all-cause mortality was comparable between culture-positive and culture-negative patients (60% and 53%, = 0.80). This pilot study represents the first comprehensive histopathological scoring method to examine the relationship between histopathologic features, culture positivity, and clinical features of pulmonary mucormycosis.
PubMed: 35448611
DOI: 10.3390/jof8040380 -
Cancers Nov 20195-Fluorouracil (5-FU) is an antimetabolite chemotherapy widely used for the treatment of various cancers. However, many cancer patients experience hematological side...
5-Fluorouracil (5-FU) is an antimetabolite chemotherapy widely used for the treatment of various cancers. However, many cancer patients experience hematological side effects following 5-FU treatment. Here, we investigated the protective effects of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a mitigator against 5-FU-induced hematologic toxicity, including neutropenia, monocytopenia, thrombocytopenia, and thrombocytosis, in Balb/c mice injected with 5-FU (100 mg/kg, i.p.). Administration of PLAG significantly and dose-dependently reduced the duration of neutropenia and improved the nadirs of absolute neutrophil counts (ANCs). Moreover, while the ANCs of all mice in the control fell to the severely neutropenic range, none of the mice in the PLAG 200 and 400 mg/kg-treated groups experienced severe neutropenia. Administration of PLAG significantly delayed the mean first day of monocytopenia and reduced the duration of monocytopenia. PLAG also effectively reduced extreme changes in platelet counts induced by 5-FU treatment, thus preventing 5-FU-induced thrombocytopenia and thrombocytosis. PLAG significantly decreased plasma levels of the chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, interleukin (IL)-6, and C-reactive protein (CRP), which were elevated consistently with the occurrence time of neutropenia, monocytopenia, and thrombocytopenia. When compared with olive oil and palmitic linoleic hydroxyl glycerol (PLH), only PLAG effectively mitigated 5-FU-induced hematological toxicity, indicating that it has a distinctive mechanism of action. In conclusion, PLAG may have therapeutic potential as a mitigator for 5-FU-induced neutropenia and other hematological disorders.
PubMed: 31752148
DOI: 10.3390/cancers11111811 -
Blood Aug 2018Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies to platelet factor 4 (PF4)/heparin complexes. PF4 released from platelets...
Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder initiated by antibodies to platelet factor 4 (PF4)/heparin complexes. PF4 released from platelets binds to surface glycosaminoglycans on hematopoietic and vascular cells that are heterogenous in composition and differ in affinity for PF4. PF4 binds to monocytes with higher affinity than to platelets, and depletion of monocytes exacerbates thrombocytopenia in a murine HIT model. Here we show that the expression of PF4 on platelets and development of thrombocytopenia are modulated by the (re)distribution of PF4 among hematopoietic and endothelial cell surfaces. Binding of PF4 to platelets in whole blood in vitro varies inversely with the white cell count, likely because of the greater affinity of monocytes for PF4. In mice, monocyte depletion increased binding of PF4 to platelets by two- to three-fold. Induction of HIT in mice caused a transient >80-fold increase in binding of HIT antibody to monocytes vs 3.5-fold increase to platelets and rapid transient monocytopenia. Normalization of monocyte counts preceded the return in platelet counts. Exposure of blood to endothelial cells also depletes PF4 from platelet surfaces. These studies demonstrate a dynamic interchange of surface-bound PF4 among hematopoetic and vascular cells that may limit thrombocytopenia at the expense of promoting prothrombotic processes in HIT.
Topics: Animals; Antigens; Blood Platelets; Gene Expression Regulation; Heparin; Human Umbilical Vein Endothelial Cells; Humans; Mice; Monocytes; Platelet Factor 4; Thrombocytopenia
PubMed: 29914979
DOI: 10.1182/blood-2018-02-830737