Chronic lymphocytic leukemia is marked by profound defects in T-cell function. Programmed death-1 is a receptor involved in tumor-mediated immunosuppression through binding of the PD-L1 ligand. ...Multiparametric flow cytometry and immunohistochemistry were used to study PD-1/PD-L1 expression. Functional assays were used to determine the involvement of the PD-1/PD-L1 axis in T-cell responses. PD-1 expression by CD4(+) and CD8(+) T lymphocytes was significantly higher in 117 chronic lymphocytic leukemia patients than in 33 donors of a comparable age. CD4(+) and CD8(+) T lymphocytes from chronic lymphocytic leukemia patients displayed increased numbers of effector memory and terminally differentiated cells, respectively, when compared to controls. The number of effector memory CD4(+) and terminally differentiated CD8(+) lymphocytes positively associated with a more advanced stage of disease, treatment requirements and unfavorable genomic aberrations. Furthermore, leukemic lymphocytes expressed higher levels of PD-L1 than circulating B lymphocytes from normal donors. PD-1 and PD-L1 surface expression spiked in proliferating T and B lymphocytes, suggesting that this interaction works efficiently in activated environments. Within chronic lymphocytic leukemia proliferation centers in the lymph node, CD4(+)/PD-1(+) T lymphocytes were found to be in close contact with PD-L1(+) chronic lymphocytic leukemia cells. Lastly, functional experiments using recombinant soluble PD-L1 and blocking antibodies indicated that this axis contributes to the inhibition of IFN-γ production by CD8(+) T cells. These observations suggest that pharmacological manipulation of the PD-1/PD-L1 axis may contribute to restoring T-cell functions in the chronic lymphocytic leukemia microenvironment.
As novel substances, short time windows, and limits of detection increasingly challenge direct methods of doping detection in sports, indirect tools inevitably take a greater role in the fight ...against it. One such tool is the athlete biological passport (ABP) – a longitudinal profiling of the measured haematological and biochemical biomarkers, combined with calculated scores, against the background of epidemiological data crucial for doping detection. In both of its modules, haematological and steroidal, ABP parameters are analysed with the Bayesian adaptive model, which individualises reference and cut-off values to improve its sensitivity. It takes into account the confounding factors with proven and potential influence on the biomarkers, such as race and altitude exposure. The ABP has already changed the fight against doping, but its importance will further grow with the new modules (e.g., endocrinological), parameters (e.g., plasma volume-independent parameters), and complementing indirect methods (e.g., transcriptomic).
During the ongoing COVID-19 epidemic many efforts have gone into the investigation of the SARS-CoV-2-specific antibodies as possible therapeutics. Currently, conclusions cannot be drawn due to the ...lack of standardization in antibody assessments. Here we describe an approach of establishing antibody characterisation in emergent times which would, if followed, enable comparison of results from different studies. The key component is a reliable and reproducible assay of wild-type SARS-CoV-2 neutralisation based on a banking system of its biological components - a challenge virus, cells and an anti-SARS-CoV-2 antibody in-house standard, calibrated to the First WHO International Standard immediately upon its availability. Consequently, all collected serological data were retrospectively expressed in an internationally comparable way. The neutralising antibodies (NAbs) among convalescents ranged from 4 to 2869 IU mL
in a significant positive correlation to the disease severity. Their decline in convalescents was on average 1.4-fold in a one-month period. Heat-inactivation resulted in 2.3-fold decrease of NAb titres in comparison to the native sera, implying significant complement activating properties of SARS-CoV-2 specific antibodies. The monitoring of NAb titres in the sera of immunocompromised COVID-19 patients that lacked their own antibodies evidenced the successful transfusion of antibodies by the COVID-19 convalescent plasma units with NAb titres of 35 IU mL
or higher.
Chronic lymphocytic leukemia (CLL) is a disease of the elderly, characterized by immunodeficiency. Hence, patients with CLL might be considered more susceptible to severe complications from COVID-19. ...We undertook this retrospective international multicenter study to characterize the course of COVID-19 in patients with CLL and identify potential predictors of outcome. Of 190 patients with CLL and confirmed COVID-19 diagnosed between 28/03/2020 and 22/05/2020, 151 (79%) presented with severe COVID-19 (need of oxygen and/or intensive care admission). Severe COVID-19 was associated with more advanced age (≥65 years) (odds ratio 3.72 95% CI 1.79-7.71). Only 60 patients (39.7%) with severe COVID-19 were receiving or had recent (≤12 months) treatment for CLL at the time of COVID-19 versus 30/39 (76.9%) patients with mild disease. Hospitalization rate for severe COVID-19 was lower (p < 0.05) for patients on ibrutinib versus those on other regimens or off treatment. Of 151 patients with severe disease, 55 (36.4%) succumbed versus only 1/38 (2.6%) with mild disease; age and comorbidities did not impact on mortality. In CLL, (1) COVID-19 severity increases with age; (2) antileukemic treatment (particularly BTK inhibitors) appears to exert a protective effect; (3) age and comorbidities did not impact on mortality, alluding to a relevant role of CLL and immunodeficiency.
To investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients.
We retrospectively analyzed the records of 3941 ...consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission.
The median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index).
RDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.
Summary
We retrospectively investigated clinical and prognostic significance of psoas muscle index (PMI) calculated as total psoas muscle area at L3 vertebra level obtained from baseline computed ...tomography (CT) scans in 49 newly diagnosed classical Hodgkinʼs lymphoma (cHL) patients prior to specific treatment. Median PMI was 572.5 mm
2
/m
2
and was significantly higher in males (
P
< 0.001), patients with higher body mass index (BMI,
P
< 0.001), absence of extranodal disease (
P
= 0.037), higher absolute lymphocyte count (
P
= 0.037), higher hemoglobin (
P
= 0.010) and lower lactate dehydrogenase (LDH,
P
= 0.050). There were no significant associations with age, disease subtype, presence of constitutional symptoms, Ann Arbor disease stage, presence of advanced disease or international prognostic score. Patients with lower PMI had significantly worse PFS (hazard ratio HR 4.91;
P
= 0.009). This phenomenon persisted in the multivariate model (HR = 5.09;
P
= 0.042) adjusted for International Prognostic Score (IPS) and chemotherapy type.
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