COVID-19 Patients Require Prolonged Extracorporeal Membrane Oxygenation Support for Survival Compared With Non-COVID-19 Patients

OBJECTIVES: To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19–related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)–related ARDS. DESIGN: Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients. SETTING: Single-center ICU. PATIENTS: Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18–58 d) versus 16 days (IQR, 19–39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6–28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9–27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7–25 d). CONCLUSIONS: COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival

The role of cell-free hemoglobin and haptoglobin in acute kidney injury in critically ill adults with ARDS and therapy with VV ECMO

Background: Increased plasma concentrations of circulating cell-free hemoglobin (CFH) are supposed to contribute to the multifactorial etiology of acute kidney injury (AKI) in critically ill patients while the CFH-scavenger haptoglobin might play a protective role. We evaluated the association of CFH and haptoglobin with AKI in patients with an acute respiratory distress syndrome (ARDS) requiring therapy with VV ECMO. Methods: Patients with CFH and haptoglobin measurements before initiation of ECMO therapy were identified from a cohort of 1044 ARDS patients and grouped into three CFH concentration groups using a risk stratification. The primary objective was to assess the association of CFH and haptoglobin with KDIGO stage 3 AKI. Further objectives included the identification of a target haptoglobin concentration to protect from CFH-associated AKI. Measurements and main results: Two hundred seventy-three patients fulfilled the inclusion criteria. Of those, 154 patients (56.4%) had AKI at ECMO initiation. The incidence of AKI increased stepwise with increasing concentrations of CFH reaching a plateau at 15 mg/dl. Compared to patients with low [= 15 mg/dl] CFH concentrations had a three- and five-fold increased risk for AKI (adjusted odds ratio [OR] moderate vs. low, 2.69 [95% CI, 1.25-5.95], P = 0.012; and OR high vs. low, 5.47 [2.00-15.9], P = 0.001). Among patients with increased CFH concentrations, haptoglobin plasma levels were lower in patients with AKI compared to patients without AKI. A haptoglobin concentration greater than 2.7 g/l in the moderate and 2.4 g/l in the high CFH group was identified as clinical cutoff value to protect from CFH-associated AKI (sensitivity 89.5% [95% CI, 83-96] and 90.2% [80-97], respectively). Conclusions: In critically ill patients with ARDS requiring therapy with VV ECMO, an increased plasma concentration of CFH was identified as independent risk factor for AKI. Among patients with increased CFH concentrations, higher plasma haptoglobin concentrations might protect from CFH-associated AKI and should be subject of future research

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

La mesure des différences morphologiques entre populations humaines : révision critique de coefficients de distance et leur partage en grandeur et en forme

Historical anthropology (physical) is becoming involved in large scale analysis: geographical and chronological. In view of this extension in scope-and in morphological variability-three current distance coefficients are examined as to their mathematical and taxonomical properties. Work was done on the data collected by Howells (1973). Penrose distances proved to be methodologically unsatisfactory (although they can produce useable results under some conditions). The size component revealed to be very sensitive (unstable) with regard to the variates choosen ; its importance with respect to shape decreases as a fonction of the number of variates. The breakdown of total distance into size and shape is arbitrary and almost depleted of morphological meaning. Generalized distance ( Mahalanobis) : if conditions for correct application are to be respected, D2 can only be used in problems of low taxonomie level (population, race, but not species). - D2 and centroid distances in discriminant space are equivalent only if discriminant analysis is carried out according to Fisher's algorithm. Centroid distances in principal component space appear to be a method of general interest and purpose since they result from a "neutral" maximisation procedure and are not affected by restrictive conditions as to their application. As for the breakdown of the total metric information into size and shape components, it is demonstrated that these two categories are surprisingly independant. More emphasis should be given to metrical assessment of shape (stereometry). A method for splitting total distance into size and shape components is presented. Substantial refinement of interpretation of anthropometrical data can be expected

Datenbanken für die historische Anthropologie : ein Votum für ein gemeinsames Vorgehen bei der Datenbeschaffung

Appel à tous les chercheurs engagés dans l'anthropologie préhistorique et historique. Ils sont invités à participer à une banque de données, ayant pour tâche de gérer (récolter, centraliser, diffuser) des données ostéométriques individuelles, ainsi que de l'information documentaire y relative (chronologie, géographie, paléodémographie, bibliographie, etc.). On démontre que la procédure actuelle d'échange de données individuelles (essentiellement par voie de publication) est inefficace, non exhaustive et inadéquate à la thématique élargie actuelle de l'anthropologie historique. En plus, son avenir est sérieusement compromis par l'augmentation continuelle du coût de l'impression. Une centralisation de l'information par une banque de données appuyée par ordinateur parait être un moyen approprié pour faire face aux exigences méthodologiques et procédurales, actuelles et futures. Un effet de rationalisation appréciable pourrait contribuer à faciliter le travail documentaire de tous les chercheurs, quelles que soient leurs habitudes personnelles de travail (par ordinateur ou non). Tous les chercheurs sont vivement invités à participer à cette banque de données, en tant que fournisseurs et en tant que récepteurs de données. Cette banque de données est opérationnelle depuis 1978

Data banks in historical anthropology : the material infrastructure for interdisciplinarity

Le présent article donne une description sommaire d'un système de banque de données destinée à fournir un apport documentaire à l'anthropologie historique. Tout d'abord on insiste sur l'importance d'une approche interdisciplinaire (avec l'archéologie) de cette recherche. Partant des desiderata concernant l'éventail des données à récolter - et tenant compte de considérations portant sur les modalités de stockage et d'édition - on esquisse brièvement la philosophie de base, la genèse et les caractéristiques du logiciel ADAM. Le but de la banque de données gérée à l'aide de ce système consiste à récolter un maximum de données morphométriques individuelles relatives à du matériel squelettique historique et préhistorique, de le compléter par une très vaste documentation (aspects culturels, géographiques, chronologiques, bibliographiques, etc.), et de le rendre disponible pour une élaboration ultérieure. Le système ADAM se caractérise par une grande souplesse quant aux données qu'on peut y entrer ainsi qu'aux possibilités de son extension future. Il n'est soumis à aucune limite chronologique ou géographique. Une grande importance a été accordée au confort et à la sécurité de son utilisation. Il a été conçu pour gérer un gros volume de données complexes. A ce jour, il contient environ 40'000 individus provenant d'environ 2'000 sites différents, dont la datation s'étend du Mésolithique aux périodes récentes (thèmes principaux: préhistoire et protohistoire de l'Eurasie, anthropologie circumpolaire, haut moyen âge de l'Europe centrale). La banque de données doit servir un cercle aussi grand que possible de participants. L'auteur se tient à la disposition de chacun pour de plus amples renseignements

A synopsis of the physical anthropology of the corded ware complex on the background of the expansion of the Kurgan cultures

Morphometrical data of human skeletal material from Eastern and Central Europe, of the period 4000 b.c. to 1800 b.c. (c. 5000-2500 B.C.), are elaborated with the aid of multivariate methods. A synoptical picture is presented describing biological affinities between the cultural groups concerned. The affinities are interpreted on the background of the geographical distances. "Old Europe" cultures are confronted a) to their local and chronological successors, and b) to populations living in, or originating from, Eastern Europe, in order to work out - on the background of current theories on Indo-Europeanization and the expansion of Kurgan cultures - the biological elements potentially implied in the formation of the Corded Ware complex. The question of the phenotypical variability of the latter is investigated with respect to time and space (expansion) ; its biological incidence on the autochthonous populations (substratum) is analyzed. In parallel, the Corded Ware complex is confronted to the Bell Beaker complex, especially as to their morphological and cultural antagonism. The great lines can be summarized as follows. Initially, two biological and geographical blocks were present: in Western Europe, the homogenuous complex of "Old Europe" populations ; in Eastern Europe the Neolithic substratum and the quite different Kurgan groups. The biological effect of the expansion of the Kurgan traditions is evident in the regions adjacent to the North Pontic area, but it is fading out progressively with increasing distance from this center. The Corded Ware complex s.I. is biologically heterogeneous. The local groups of the core area (Central Germany, Czechoslovakia, Poland) form a very homogeneous block, issued from the local "Old Europe" substratum and persisting until Aunjetitz at least. This block shows no biological affinities to the Ukrainian Kurgan populations. There is no evidence for physical presence of Kurgan tribes in this area. Indo-Europeanization of Northern Europe could be explained by indirect Kurganization, i.e. by invasion of previously Kurganized neighbor groups