Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection

IntroductionStress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19. MethodsIn a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission. ResultsPatients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-alpha), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR <= 1.14. IL-10, IL-10/TNF-alpha ratio, CXCL10, and IFN-gamma were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-alpha ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078-6.012) and death (OR 2.281; CI 1.049-7.369) independently of diabetes and other major confounders. ConclusionsIn patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis

The Role of Allogeneic Transplantation in Chronic Myeloid Leukemia in 2023: A Case-Based Concise Review

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), granting patients a life expectancy close to that of the normal population and, in a subset of patients, the possibility to discontinue therapy. Nonetheless, for a not negligible minority of patients, TKIs are not able to control CML. Allogeneic hematopoietic cell transplantation (HCT) has long been a pivotal therapy for CML. At present, allogeneic HCT is considered an option in CML patients diagnosed or progressing to blast phase (BP), for those in chronic phase (CP) resistant to multiple lines of TKI therapy or for those experiencing severe toxicity, mostly hematologic, under TKIs. Moving from real-world cases, we reviewed the results of allogeneic HCT in the setting of advanced-phase CML or failure of TKIs, with a focus on the progresses in transplant technology that has extended transplant options in elderly CML patients and in those lacking a sibling donor, and on the post-HCT strategies for prevention and treatment of disease relapse

Combining Deep Phenotyping of Serum Proteomics and Clinical Data via Machine Learning for COVID-19 Biomarker Discovery

The persistence of long-term coronavirus-induced disease 2019 (COVID-19) sequelae demands better insights into its natural history. Therefore, it is crucial to discover the biomarkers of disease outcome to improve clinical practice. In this study, 160 COVID-19 patients were enrolled, of whom 80 had a “non-severe” and 80 had a “severe” outcome. Sera were analyzed by proximity extension assay (PEA) to assess 274 unique proteins associated with inflammation, cardiometabolic, and neurologic diseases. The main clinical and hematochemical data associated with disease outcome were grouped with serological data to form a dataset for the supervised machine learning techniques. We identified nine proteins (i.e., CD200R1, MCP1, MCP3, IL6, LTBP2, MATN3, TRANCE, α2-MRAP, and KIT) that contributed to the correct classification of COVID-19 disease severity when combined with relative neutrophil and lymphocyte counts. By analyzing PEA, clinical and hematochemical data with statistical methods that were able to handle many variables in the presence of a relatively small sample size, we identified nine potential serum biomarkers of a “severe” outcome. Most of these were confirmed by literature data. Importantly, we found three biomarkers associated with central nervous system pathologies and protective factors, which were downregulated in the most severe cases

Rapid response to the earthquake emergency of May 2012 in the Po Plain, northern Italy

Rapid-response seismic networks are an important element in the response to seismic crises. They temporarily improve the detection performance of permanent monitoring systems during seismic sequences. The improvement in earthquake detection and location capabilities can be important for decision makers to assess the current situation, and can provide invaluable data for scientific studies related to hazard, tectonics and earthquake physics. Aftershocks and the clustering of the locations of seismic events help to characterize the dimensions of the causative fault. Knowing the number, size and timing of the aftershocks or the clustering seismic events can help in the foreseeing of the characteristics of future seismic sequences in the same tectonic environment. Instrumental rapid response requires a high degree of preparedness. A mission in response to a magnitude (ML) 6 event with a rupture length of a few tens of kilometers might involve the deployment within hours to days of 30-50 seismic stations in the middle of a disaster area of some hundreds of square kilometers, and the installation of an operational center to help in the logistics and communications. When an earthquake strikes in a populated area, which is almost always the case in Italy, driving the relevant seismic response is more difficult. Temporary station sites are chosen such as to optimize the network geometry for earthquake locations and source study purposes. Stations have to be installed in quiet, but easily reachable, sites, and for real-time data transmission, the sites might need to have optical intervisibility. The operational center can remain in a town if there is one within the damaged area, and it should coordinate the actions of the field teams and provide information to colleagues, the Civil Protection Authorities and the general public. The emergency system should operate as long as the seismic rate remains high; the duration of any mission might also depend on the seismic history of the area involved. This study describes the seismic response following the May 20, 2012, ML 5.9 earthquake in northern Italy, which included rapid deployment of seismological stations in the field for real-time seismic monitoring purposes, the coordination of further instrumental set-ups according to the spatial evolution of the seismic sequence, and data archiving

Guidelines for the use of flow cytometry and cell sorting in immunological studies

International audienceThe classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127(-) and CD127(+) early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127(-) and CD127(+) ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127(-) ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127(+) ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis