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Microorganisms May 2023Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1...
Unusual viral skin infections might be the first clinical manifestation in children with an inborn error of immunity (IEI). We performed a prospective study from 1 October 2017 to 30 September 2021, at the Department of Pediatric Infectious Diseases and Clinical Immunity of Ibn Rochd University Hospital-Casablanca. During this period, on 591 patients newly diagnosed with a probable IEI, eight of them (1.3%), from six independent families, had isolated or syndromic unusual viral skin infections, which were either profuse, chronic or recurrent infections, and resistant to any treatment. The median age of disease onset was nine years old and all patients were born from a first-degree consanguineous marriage. By combining clinical, immunological and genetic investigations, we identified GATA2 deficiency in one patient with recalcitrant profuse verrucous lesions and monocytopenia (1/8) and STK4 deficiency in two families with HPV lesions, either flat or common warts, and lymphopenia (2/8), as previously reported. We also identified COPA deficiency in twin sisters with chronic profuse Molluscum contagiosum lesions, pulmonary diseases and microcytic hypochromic anemia (2/8). Finally, we also found one patient with chronic profuse MC lesions and hyper IgE syndrome, (1/8) and two patients with either recalcitrant profuse verrucous lesions or recurrent post-herpetic erythema multiforme and a combined immunodeficiency (2/8) with no genetic defect identified yet. Raising clinicians awareness that infectious skin diseases might be the consequence of an inborn error of immunity would allow for optimized diagnosis, prevention and treatment of patients and their families.
PubMed: 37317175
DOI: 10.3390/microorganisms11051202 -
Thrombosis Research Aug 2023Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical,...
INTRODUCTION
Tissue factor expression on monocytes is implicated in the pathophysiology of sepsis-induced coagulopathy. How tissue factor is expressed by monocyte subsets (classical, intermediate and non-classical) is unknown.
METHODS
Monocytic tissue factor surface expression was investigated during three conditions. Primary human monocytes and microvascular endothelial cell co-cultures were used for in vitro studies. Volunteers received a bolus of lipopolysaccharide (2 ng/kg) to induce endotoxemia. Patients with sepsis, or controls with critical illness unrelated to sepsis, were recruited from four intensive care units.
RESULTS
Contact with endothelium and stimulation with lipopolysaccharide reduced the proportion of intermediate monocytes. Lipopolysaccharide increased tissue factor surface expression on classical and non-classical monocytes. Endotoxemia induced profound, transient monocytopenia, along with activation of coagulation pathways. In the remaining circulating monocytes, tissue factor was up-regulated in intermediate monocytes, though approximately 60 % of individuals (responders) up-regulated tissue factor across all monocyte subsets. In critically ill patients, tissue factor expression on intermediate and non-classical monocytes was significantly higher in patients with established sepsis than among non-septic patients. Upon recovery of sepsis, expression of tissue factor increased significantly in classical monocytes.
CONCLUSION
Tissue factor expression in monocyte subsets varies significantly during health, endotoxemia and sepsis.
Topics: Humans; Monocytes; Endotoxemia; Thromboplastin; Thromboinflammation; Lipopolysaccharides; Sepsis
PubMed: 37263122
DOI: 10.1016/j.thromres.2023.05.018 -
Acta Informatica Medica : AIM : Journal... Mar 2023Coronavirus disease 2019 (COVID-19) can cause a wide clinical spectrum, ranging from asymptomatic to severe disease with a high mortality rate. In view of the current...
BACKGROUND
Coronavirus disease 2019 (COVID-19) can cause a wide clinical spectrum, ranging from asymptomatic to severe disease with a high mortality rate. In view of the current pandemic and the increasing influx of patients into healthcare facilities, there is a need to identify simple and reliable tools for stratifying patients.
OBJECTIVE
Study aimed to analyze whether hemogram-derived ratios (HDRs) can be used to identify patients with a risk of developing a severe clinical form and admission to hospital.
METHODS
This cross-sectional and observational study included 500 patients with a confirmed diagnosis of COVID-19. Data on clinical features and laboratory parameters were collected from medical records and 13 HDRs were calculated and analyzed. Descriptive and inferential statistics were included in the analysis.
RESULTS
Of the 500 patients, 43.8% had a severe form of the disease. Lymphocytopenia, monocytopenia, higher C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were found in severe patients ( < 0.05). Significantly higher neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), neutrophil-to-platelet ratio (NPR), neutrophil-to-lymphocyte-to-platelet ratio (NLPR) and CRP-to-lymphocyte ratio (CRP/Ly) values were found in severe patients ( < 0.001). In addition, they have statistically significant prognostic potential ( < 0.001). The area under the curve (AUC) for CRP/Ly, dNLR, NLPR, NLR, and NPR were 0.693, 0.619, 0.619, 0.616, and 0.603, respectively. The sensitivity and specificity were 65.7% and 65.6% for CRP/Ly, 51.6% and 70.8 for dNLR, 61.6% and 57.3% for NLPR, 40.6% and 80.4% for NLR, and 48.8% and 69.1% for NPR.
CONCLUSION
The results of the study suggest that NLR, dNLR, CRP/Ly, NPR, and NLPR can be considered as potentially useful markers for stratifying patients with a severe form of the disease. HDRs derived from routine blood tests results should be included in common laboratory practice since they are readily available, easy to calculate, and inexpensive.
PubMed: 37038490
DOI: 10.5455/aim.2023.31.41-47 -
Vaccines Jan 2023Lumpy skin disease (LSD) is a highly infectious disease of cattle caused by a virus of the Poxviridae family, genus Capripoxvirus. The present study was designed to...
Insights into the Prognostic Role of Serum Interleukin-6 and Hematobiochemical Alterations in Cattle during Recent Outbreaks of Lumpy Skin Disease in Lodhran District, Pakistan.
Lumpy skin disease (LSD) is a highly infectious disease of cattle caused by a virus of the Poxviridae family, genus Capripoxvirus. The present study was designed to determine the prognostic ability of serum IL-6 in LSD using a binary logistic regression model at baseline sampling. A 17-day cohort study was conducted on a recent outbreak of LSD among cattle in the Lodhran District of Punjab, Pakistan. Infected cattle were divided into two categories based on their clinical status on day 17 as recovered ( = 33) or unrecovered ( = 17). Nodular lesions and scab specimens ( = 50) were used for the isolation of the lumpy skin disease virus and were confirmed by PCR. In recovered animals, hematological results showed marked leukocytosis, eosinophilia, lymphocytosis, neutrophilia, and monocytopenia. However, marked erythrocytosis, leukopenia, and thrombocytopenia were observed in the unrecovered animals at the final sampling point of the study. Serum levels of total protein, albumin, and glucose were significantly higher in the recovered animals. Meanwhile, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, creatinine phosphokinase, total bilirubin, and direct bilirubin were found considerably higher in the unrecovered group. Receiver-operating characteristic curve analysis for serum IL-6 at baseline predicts the extended clinical conditions at the cut-off value of 85.16 pg/mL (55% specificity, 94% sensitivity, area under the curve 0.8039, respectively). In conclusion, the disease-induced hematological and biochemical alterations were significantly ameliorated in the recovered animals. In addition, the study revealed that serum IL-6 can be used as a valid marker for predicting the clinical worsening of LSD in cattle.
PubMed: 36679958
DOI: 10.3390/vaccines11010113 -
International Journal of Molecular... Jan 2023Colorectal cancer is the fourth most common cancer worldwide and the third most frequently diagnosed form of cancer associated with high mortality rates. Recently,...
Colorectal cancer is the fourth most common cancer worldwide and the third most frequently diagnosed form of cancer associated with high mortality rates. Recently, targeted drug delivery systems have been under increasing attention owing to advantages such as high therapeutic effectiveness with a significant depletion in adverse events. In this report, we describe the biocompatible and thermoresponsive FA-conjugated PHEA--PNIPAAm copolymers as nanocarriers for the delivery of 5-FU. The block copolymers were obtained using RAFT (Reversible Addition-Fragmentation chain Transfer) polymerization and were characterized by methods such as SEC (Size Exclusion Chromatography), NMR (Nuclear Magnetic Resonance), UV-Vis (Ultraviolet-Visible), FT-IR (Fourier Transform Infrared) spectroscopy, and TGA (Thermogravimetric Analysis). Nanoparticles were formed from polymers with and without the drug-5-fluorouracil, which was confirmed using DLS (Dynamic Light Scattering), zeta potential measurements, and TEM (Transmission Electron Microscopy) imaging. The cloud points of the polymers were found to be close to the temperature of the human body. Eventually, polymeric carriers were tested as drug delivery systems for the safety, compatibility, and targeting of colorectal cancer cells (CRC). The biological evaluation indicated high compatibility with the representative host cells. Furthermore, it showed that proposed nanosystems might have therapeutic potential as mitigators for 5-FU-induced monocytopenia, cardiotoxicity, and other chemotherapy-associated disorders. Moreover, results show increased cytotoxicity against cancer cells compared to the drug, including a line with a drug resistance phenotype. Additionally, the ability of synthesized carriers to induce apoptosis and necrosis in treated CRC cells has been confirmed. Undoubtedly, the presented aspects of colorectal cancer therapy promise future solutions to overcome the conventional limitations of current treatment regimens for this type of cancer and to improve the quality of life of the patients.
Topics: Humans; Fluorouracil; Drug Carriers; Folic Acid; Spectroscopy, Fourier Transform Infrared; Quality of Life; Polymers; Drug Delivery Systems; Nanoparticles; Colorectal Neoplasms
PubMed: 36674883
DOI: 10.3390/ijms24021364 -
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 -
Scientific Reports Oct 2022Monocytopenia is a common finding in patients with myelodysplastic syndrome (MDS), but although monocytes may exhibit prognostic significance in MDS due to their role in...
Monocytopenia is a common finding in patients with myelodysplastic syndrome (MDS), but although monocytes may exhibit prognostic significance in MDS due to their role in innate immunity, they have not been incorporated in any prognostic scoring system for MDS. In this study, we analyzed national registry data from 1719 adults with MDS. Monocytopenia was present in 29.5% of the patients and was correlated with the presence of excess blasts and higher revised international prognostic scoring system categories. Univariate analysis showed that monocytopenia was prognostic of a lower overall survival [(OS), 32.0 versus 65.0 months, p < 0.001], while it retained its prognostic significance in a multivariate model comprising anemia, neutropenia and thrombocytopenia [hazard ratio (HR) for OS, 1.320, p < 0.001]. Moreover, it was prognostic of a lower leukemia free survival (LFS) both in univariate analysis and in a multivariate model comprising cytopenias, bone marrow blasts, and cytogenetic risk (HR for LFS 1.27, p = 0.031). The findings regarding OS and LFR were exclusive or more pronounced in lower risk patients, respectively. Moreover, monocytopenia could divide the low and intermediate risk groups of IPSS-R in prognostically distinct subgroups. Our results redefine the prognostic role of monocytes in MDS and set the basis for further studies to validate our results and expand our knowledge on the prognostic significance of monocytopenia in MDS.
Topics: Adult; Humans; Prognosis; Myelodysplastic Syndromes; Bone Marrow; Proportional Hazards Models; Thrombocytopenia; Neutropenia
PubMed: 36289284
DOI: 10.1038/s41598-022-21933-7 -
Medicine Sep 2022Although some studies have reported prognostic factors for coronavirus disease 2019 (COVID-19), they were conducted before standard treatment with remdesivir and... (Observational Study)
Observational Study
Although some studies have reported prognostic factors for coronavirus disease 2019 (COVID-19), they were conducted before standard treatment with remdesivir and dexamethasone was implemented. This retrospective, observational study was conducted to evaluate various prognostic factors in patients with COVID-19 pneumonia receiving standard treatment with remdesivir and dexamethasone. Of 99 patients with COVID-19 pneumonia, 68 (68.7%) died within 30 days of hospitalization. The mean age was 71.3 years. Remdesivir and dexamethasone were administered to 80 (80.8%) and 84 (84.8%) patients, respectively. Early antibiotic treatment was administered to 70 patients (70.7%) within 5 days of hospitalization. Dexamethasone (79.4% vs 96.8%, P = .033) was more frequently administered in the survived group, whereas early antibiotics (60.3% vs 93.5%, P = .001) were less frequently administered. In the multivariate analysis, a high National Early Warning Score (NEWS; odds ratio [OR] 1.272), high Charlson Comorbidity Index (CCI; OR 1.441), and dyspnea (OR 4.033) were independent risk factors for 30-day mortality. There was no significant difference in age, sex, and vaccination doses between the survived and fatal groups. Lymphopenia, monocytopenia and high levels of C-reactive protein (CRP)/lactate dehydrogenase (LDH) reflected poor prognosis. NEWS, CCI, and dyspnea were predictors of 30-day mortality in patients with COVID-19 pneumonia. Early antibiotic use did not lower the 30-day mortality risk.
Topics: Adenosine Monophosphate; Aged; Alanine; Anti-Bacterial Agents; C-Reactive Protein; Dexamethasone; Dyspnea; Humans; Lactate Dehydrogenases; Pneumonia; Prognosis; Retrospective Studies; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 36197235
DOI: 10.1097/MD.0000000000030474