Plasma concentrations of von Willebrand factor and intracellular adhesion molecule-1 for prediction of outcome after successful cardiopulmonary resuscitation

OBJECTIVE: Ischemia/reoxygenation following cardiopulmonary resuscitation might cause endothelial injury/activation that could contribute to an adverse outcome after cardiopulmonary resuscitation. We studied plasma concentrations of von Willebrand factor (vWF) antigen and soluble intracellular adhesion molecule (sICAM)-1 as markers of a generalized endothelial injury/activation in relation to outcome after cardiopulmonary resuscitation. DESIGN: Retrospective study on stored plasma samples. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty-five patients who survived >24 hrs after in- or out-of-hospital cardiopulmonary resuscitation and 15 noncritically ill control patients.I NTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of vWF antigen and sICAM-1 on day 2 after cardiopulmonary resuscitation were higher in patients than in controls (p < .001 and p = .001, respectively). In-hospital cardiopulmonary resuscitation, cardiopulmonary resuscitation duration > or = 15 mins, severe cardiovascular failure, and renal dysfunction/failure at the time of blood sampling were associated with significant elevations in vWF antigen and sICAM-1 concentrations. Patients with an unfavorable outcome after cardiopulmonary resuscitation (cerebral performance category > or = 3) exhibited higher vWF antigen and sICAM-1 concentrations than patients with good outcome (cerebral performance category 1-2; p < .001 and p = .097, respectively). Renal dysfunction/failure, severe cardiovascular failure, systemic inflammatory response syndrome, and cardiopulmonary resuscitation duration > or = 15 mins were also associated with higher adverse outcome rates. Combination of these four variables into a cardiac arrest risk score (levels 0-4) showed adverse outcome rates of 100, 56, and 0% in patients with arrest scores of 4, 2-3, and 0-1, respectively. A vWF antigen concentration >166% was an independent predictor of outcome after cardiopulmonary resuscitation (p = .002) and was associated with increased adverse outcome rates in patients with cardiac arrest risk scores of 2-3. Furthermore, both vWF antigen concentrations >166% and sICAM-1 concentrations >500 ng/mL had 100% specificity for an adverse outcome in patients after out-of-hospital cardiopulmonary resuscitation but were less predictive in patients after in-hospital cardiopulmonary resuscitation. CONCLUSIONS: vWF antigen and sICAM-1 might be useful adjunctive variables for early determination of outcome in patients after successful out-of-hospital cardiopulmonary resuscitation.     

Patients With Malignant Lymphoma and HIV Infection Experiencing Remission After First-Line Treatment Have an Excellent Prognosis

BackgroundMalignant lymphoma is still the leading cause of death among AIDS-related diseases.Patients and MethodsWe performed a retrospective analysis of 50 HIV-positive lymphoma patients. The median interval between HIV and malignant lymphoma diagnosis was 4 years. Eight patients (16%) had Hodgkin lymphoma and 42 (84%) non-Hodgkin lymphoma. Among non-Hodgkin lymphoma patients, diffuse large B-cell lymphoma (n = 18, 42%), Burkitt lymphoma (n = 11, 26%), and plasmoblastic lymphoma (n = 5, 12%) were the most frequent entities.ResultsLymphoma was treated according to standard protocols. Forty-four patients (88%) received combination antiretroviral therapy, 2 (4%) were not treated, and in 4 (8%) the HIV treatment status was not clarified. Response to first-line therapy was complete response (CR) in 24 (56%), partial response (PR) in 15 (35%), and stable disease in 1 (2%). Three patients (7%) developed progressive disease, and 9 (18%) experienced relapse after CR or PR. At a median observation period of 31 (range, 0.4-192) months, the 1-, 2-, and 5-year overall survival was 87%, 79%, and 76%, respectively. At univariate analysis, remission status after first-line treatment was predictive of outcome, as the 2-year overall survival was 95%, 66%, and 0 for patients with CR, with PR, and with progressive disease (P < .001). Results of the multivariate analysis revealed lactate dehydrogenase concentration at lymphoma diagnosis (P = .046) and relapse (P = .050) to be independent factors for overall survival.ConclusionFirst-line treatment of lymphoma in HIV positive patients is crucial. Patients who experienced and maintained a first CR had a favorable prognosis.     

NK cell receptor and ligand composition influences the clearance of SARS-CoV-2

To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry–based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection.