early marker
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2022 ◽  
Vol 79 (2) ◽  
Author(s):  
Jean Fausto de Carvalho Paulino ◽  
Caléo Panhoca de Almeida ◽  
Isabella Laporte Santos ◽  
João Guilherme Ribeiro Gonçalves ◽  
Sérgio Augusto Morais Carbonell ◽  
...  

Author(s):  
Patricia Pastoriza-Domínguez ◽  
Iván G. Torre ◽  
Faustino Diéguez-Vide ◽  
Isabel Gómez-Ruiz ◽  
Sandra Geladó ◽  
...  

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 797
Author(s):  
Subramanian Senthilkumaran ◽  
Ketan Patel ◽  
Anika Salim ◽  
Pradeep Vijayakumar ◽  
Harry F. Williams ◽  
...  

Snakebite-induced acute kidney injury (AKI) is frequently observed in patients following bites from vipers such as Russell’s viper (Daboia russelii) in India. Currently, the levels of serum creatinine are mainly used as a marker to determine the necessity for renal replacement therapy (RRT) (haemodialysis) in severe cases of AKI. However, it takes up to 48 h to ascertain a distinct change in creatinine levels compared to its baseline level upon admission. The time lost between admission and the 48 h timepoint significantly affects the clinical management of snakebite victims. Moreover, early diagnosis of AKI and decision on the necessity for RRT in snakebite victims is critical in saving lives, reducing long-term complications, and minimising treatment costs arising from expensive haemodialysis. Neutrophil gelatinase–associated lipocalin (NGAL) has been recently studied as a robust early marker for AKI in non-snakebite patients. However, its suitability for clinical use in snakebite victims has not been rigorously established. Here, we demonstrate the clinical significance of plasma NGAL as a robust marker for RRT following AKI using a large cohort (309) of Russell’s viper victims without any pre-existing health conditions. NGAL levels upon admission are positively correlated with creatinine levels at 48 h in different stages of AKI. Overall, NGAL acts as a robust early marker to ascertain the need for RRT following Russell’s viper bites. The quantification of NGAL can be recommended as a routine test in hospitals that treat snakebites to decide on RRT at early time points instead of waiting for 48 h to confirm the increase in creatinine levels. The diagnostic use of NGAL in Russell’s viper victims with pre-existing comorbidities and for other vipers should be evaluated in future studies.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4467-4467
Author(s):  
Simona Pagliuca ◽  
Carmelo Gurnari ◽  
Tariq Kewan ◽  
Waled Bahaj ◽  
Keman Zhang ◽  
...  

Abstract Immunotherapy-based regimens are now integrated in clinical practice for a wide range of cancers. However, responses to immunotherapy are inconsistent across the neoplastic spectrum. To this end, a deep characterization of intra-tumor immune architecture is essential for identifying subsets of patients who can benefit from checkpoint inhibitors and other immunomodulatory treatments. V-domain Ig suppressor of T-cell activation (VISTA) has recently been recognized as a key negative immune regulator of anti-tumor immune response and is gaining growing interest as a potential pharmacological target. This molecule can work either as a receptor or as a ligand, is highly expressed in hematopoietic stem cells and myeloid compartment (Fig.1A) and has been found upmodulated in acute myeloid leukemia (AML). 1 However, despite those features, and its compelling role as a mediator of immune escape in cancer, VISTA-associated immune features are relatively unexplored in myeloid malignancies. Herein, we conducted a large multi-omics study, investigating the transcriptomic and genetic signatures associated with VISTA expression in a large publicly available dataset of patients with AML 2 with the purpose of potentially inspiring selective molecular targeted therapies in defined subsets of patients. VISTA was found upregulated in 285 samples from AML patients at diagnosis compared to 33 specimens from healthy controls (HC) (Fig.1B) highlighting its dysregulation at disease onset. When exploring distinct AML subtypes, we observed a pattern reflecting the expression reported in normal myelopoiesis stages, with higher expression levels in myelomonocytic and monocytic subsets and lower levels in promyelocytic leukemia (Fig.1A,B). Accordingly, genomic aberrations associated with higher VISTA expression were more commonly NPM1 mutations and MLLT3-KTM2A gene fusions both enriching M4 and M5 morphologic subgroups respectively (Fig.1C, D). This pattern was also confirmed in a panel of human leukemia cell lines (Fig.1E). Based on the 75%ile of VISTA mRNA expression in HC, we categorized patients in high (N=139) and low (N=146) expressors and performed a differential analysis between the two groups. High VISTA expressors showed a striking enrichment in genes involved in immune activation with upregulation of antigen presentation and processing pathways, cytokine and interleukine signaling, toll-like receptor cascade, NK cytotoxicity and response to interferon (Fig.1F,G). Based on these findings, we reasoned that VISTA hyperexpression could arise from two possible mechanisms: I) a paraphenomenon of the enrichment in blasts with particular morphologic features, II) a feedback response to the initial immune activation against leukemic blasts, in patients with higher immunoediting potential, representing an early marker of immune pressure, shaping leukemia ontogeny. To further test this last hypothesis, we analyzed the correlation between VISTA expression and the mutational burden present in those AML specimens and found that high VISTA expression inversely correlated with the number of somatic hits acquired at diagnosis (Fig.1H). Consistent with lessons inherited from tumor biology, this result potentially indicates that VISTA hyperexpression counteracts immunoediting mechanisms that, in an initial phase, sculpt the oncogenic potential of leukemic blasts, selecting clones with lower neoantigenic burden. This phase of immune activation and elimination, is ideally followed by an equilibrium and escape stage, in which regulatory negative mechanisms arise, ultimately facilitating leukemic progression. Of note is that unbiased differential analysis of the same AML subset compared to HC did not identify upregulation in any other antigen presenting cell-associated checkpoint negative regulators, including PDL1. Altogether those findings pinpoint the role of VISTA as early marker of immune activation and potentially a feedback mechanism that ultimately may promote immune escape in AML. Targeting VISTA may be an effective approach for controlling disease recurrence and treatment resistance in molecularly defined subgroups of AML. Ongoing experiments and analysis of immunogenomic players of immune escape in the setting of allogenic stem cell transplantation will clarify the role of VISTA in mediating AML relapse and evasion from graft versus leukemia effect. Figure 1 Figure 1. Disclosures Maciejewski: Regeneron: Consultancy; Novartis: Consultancy; Bristol Myers Squibb/Celgene: Consultancy; Alexion: Consultancy.


2021 ◽  
Vol 8 (11) ◽  
pp. 3381
Author(s):  
Ruby Kataria ◽  
M. Quamar Azam ◽  
Geeta Negi ◽  
Ajay Kumar ◽  
Bhaskar Sarkar ◽  
...  

Background: Coagulopathy following major trauma is conventionally attributed to activation of coagulation factors. We hypothesized that early coagulopathy is due to tissue hypoperfusion and investigated thrombomodulin (TM) as early marker of endothelial injury in poly trauma patient.Methods: This was a prospective cohort study of major trauma patients admitted to a single trauma center. Blood was drawn within 10 minutes of arrival for analysis of TM. We assess its association with blood transfusion, length of hospital stays and mortality.Results: A total of 90 patients were enrolled. An increasing lactate was associated with high soluble TM. High TM was significantly associated with increased mortality, blood transfusion requirements, hospital stay.Conclusions: Acute traumatic coagulopathy (ATC) occurs only in the presence of tissue hypoperfusion which we have measured in form of lactate and coagulopathy measured using international normalized ratio (INR) as standard. Admission serum TM can be predictive of clinical outcomes following major trauma.


Author(s):  
Bánk G. Fenyves ◽  
Arnav Mehta ◽  
Kyle R. Kays ◽  
Caroline Beakes ◽  
Justin Margolin ◽  
...  
Keyword(s):  

2021 ◽  
Vol 429 ◽  
pp. 118288
Author(s):  
Luigi Albano ◽  
Federica Agosta ◽  
Silvia Basaia ◽  
Camilla Cividini ◽  
Tanja Stojkovic ◽  
...  

2021 ◽  
Vol 85 (2) ◽  
pp. 4046-4051
Author(s):  
Esam Eldin Mahmoud Lotfy ◽  
Mohammed Fouad Ahmed Ayoub ◽  
Lamiaa Abd Elwahab Mohamed ◽  
Hesham Mohamed Mitwally Elsayed

2021 ◽  
Author(s):  
Hailong He ◽  
Angelos Karlas ◽  
Nikolina-Alexia Fasoula ◽  
Michael Kallmayer ◽  
Juan Aguirre ◽  
...  

Microvascular endothelial dysfunction (ED) precedes the ED in larger arteries and is an early marker of cardiovascular disease (CVD). While precise assessment of microvascular ED could thus be used for the early detection and risk stratification of CVD, detailed interrogation of skin microvascular ED is limited by the technology available. Herein, we applied a novel approach for the non-invasive assessment of skin microvascular ED by developing fast plane raster-scan optoacoustic mesoscopy (FP-RSOM) to visualize and quantify skin microvasculature perfusion changes during post-occlusive hyperemia (PORH) tests. We combined static three-dimensional RSOM imaging with fast dynamic FP-RSOM measurements (1 frame / second) in human skin in vivo, which allowed for the first time to fully visualize the cutaneous microvascular response and further quantify changes of individual vessel diameter, total blood volume and vessel density during the PORH process. We further computed biomarkers from FP-RSOM images to quantify skin endothelial function within different skin layers as a function of skin depth, while conventional approaches mainly measure overall changes within sampled tissue volumes. FP-RSOM applied on smokers and patients with CVD showed clear ED in both groups compared to healthy volunteers. Moreover, FP-RSOM imaging showed higher sensitivity in quantifying the effects of smoking and CVD on skin microvascular endothelial function compared to clinically used laser Doppler flowmetry and tissue spectrometry (O2C). Our study introduces FP-RSOM as a novel tool to visualize and quantify skin microvascular ED as an early marker for the diagnostics and monitoring of cardiovascular risk and disease.


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