Outcomes of patients with hematologic malignancies and COVID-19: A systematic review and meta-analysis of 3377 patients

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched Pubmed and EMBASE up to August 20, 2020, to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of ICU admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RR), and 95% confidence intervals (CI) were calculated using a random-effects model. 34 adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14/34 adult studies included only hospitalized patients). The risk of death amongst adult patients was 34% (95% CI 28-39, N=3240) in this sample of predominantly hospitalized patients. Patients aged >60 years had a significantly higher risk of death than patients 60 years have significantly higher mortality, and pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death

Spatio-temporal Models of Lymphangiogenesis in Wound Healing

Several studies suggest that one possible cause of impaired wound healing is failed or insufficient lymphangiogenesis, that is the formation of new lymphatic capillaries. Although many mathematical models have been developed to describe the formation of blood capillaries (angiogenesis), very few have been proposed for the regeneration of the lymphatic network. Lymphangiogenesis is a markedly different process from angiogenesis, occurring at different times and in response to different chemical stimuli. Two main hypotheses have been proposed: 1) lymphatic capillaries sprout from existing interrupted ones at the edge of the wound in analogy to the blood angiogenesis case; 2) lymphatic endothelial cells first pool in the wound region following the lymph flow and then, once sufficiently populated, start to form a network. Here we present two PDE models describing lymphangiogenesis according to these two different hypotheses. Further, we include the effect of advection due to interstitial flow and lymph flow coming from open capillaries. The variables represent different cell densities and growth factor concentrations, and where possible the parameters are estimated from biological data. The models are then solved numerically and the results are compared with the available biological literature.Comment: 29 pages, 9 Figures, 6 Tables (39 figure files in total

Tumor Angiogenesis and Vascular Patterning: A Mathematical Model

Understanding tumor induced angiogenesis is a challenging problem with important consequences for diagnosis and treatment of cancer. Recently, strong evidences suggest the dual role of endothelial cells on the migrating tips and on the proliferating body of blood vessels, in consonance with further events behind lumen formation and vascular patterning. In this paper we present a multi-scale phase-field model that combines the benefits of continuum physics description and the capability of tracking individual cells. The model allows us to discuss the role of the endothelial cells' chemotactic response and proliferation rate as key factors that tailor the neovascular network. Importantly, we also test the predictions of our theoretical model against relevant experimental approaches in mice that displayed distinctive vascular patterns. The model reproduces the in vivo patterns of newly formed vascular networks, providing quantitative and qualitative results for branch density and vessel diameter on the order of the ones measured experimentally in mouse retinas. Our results highlight the ability of mathematical models to suggest relevant hypotheses with respect to the role of different parameters in this process, hence underlining the necessary collaboration between mathematical modeling, in vivo imaging and molecular biology techniques to improve current diagnostic and therapeutic tools

Association of NOD/CARD15 variants with Crohn's disease in a Greek population

Objective Single nucleotide polymorphisms in the NOD2/ CARD15 gene have recently been shown to be associated with Crohn’s disease (CD), but whether this susceptibility extends to all ethnic groups and geographic areas remains unknown. The aim of the present study was to evaluate the NOD2/CARD15 mutations in Greek patients with CD. Methods Individuals were genotyped for three NOD2/ CARD15 mutations: R702W, G908R and L1007fsinsC. Blood samples were obtained from 120 patients with CD, 85 patients with ulcerative colitis, and 100 unrelated healthy controls. Results Mutations in NOD2/CARD15 were observed with significantly greater frequency in CD patients (98/120, 81.7%) than in ulcerative colitis patients (40/85, 47%) (P < 0.0001) or in healthy individuals (21/100, 21 %) (P < 0.0001). For CD patients, compared with controls, the odds were increased for carriage of the R702W (odds ratio, 12.25) and less for the G908R (odds ratio, 5.2) and Ll007fsinsC (odds ratio, 3.9) mutations. The age of onset of CD was lower in Greek mutation carriers as compared with non-carriers of Greek origin (28.2 +/- 14.6 years versus 34 +/- 12.3 years, respectively; P = 0.036). Additionally, the frequency of NOD2/CARD15 mutations was increased in ileitis or ileocolitis compared with non-ileal disease. Conclusions The NOD2/CARD15 mutations are risk factors for CD in Greece, they appear to predict an earlier age of onset and are associated particularly with ileitis or ileocolitis. (C) 2004 Lippincott Williams Wilkins

Outcomes of patients with hematologic malignancies and COVID-19: a systematic review and meta-analysis of 3377 patients

Outcomes for patients with hematologic malignancy infected with COVID-19 have not been aggregated. The objective of this study was to perform a systematic review and meta-analysis to estimate the risk of death and other important outcomes for these patients. We searched Pubmed and EMBASE up to August 20, 2020, to identify reports of patients with hematologic malignancy and COVID-19. The primary outcome was a pooled mortality estimate, considering all patients and only hospitalized patients. Secondary outcomes included risk of ICU admission and ventilation in hospitalized patients. Subgroup analyses included mortality stratified by age, treatment status, and malignancy subtype. Pooled prevalence, risk ratios (RR), and 95% confidence intervals (CI) were calculated using a random-effects model. 34 adult and 5 pediatric studies (3377 patients) from Asia, Europe, and North America were included (14/34 adult studies included only hospitalized patients). The risk of death amongst adult patients was 34% (95% CI 28-39, N=3240) in this sample of predominantly hospitalized patients. Patients aged >60 years had a significantly higher risk of death than patients <60 years (RR 1.82, 95% CI 1.45-2.27, N=1169). The risk of death in pediatric patients was 4% (95% CI 1-9, N=102). The RR of death comparing patients with recent systemic anti-cancer therapy to no treatment was 1.17 (95% CI 0.83-1.64; N=736). Adult patients with hematologic malignancy and COVID-19, especially hospitalized patients, have a high risk of dying. Patients >60 years have significantly higher mortality, and pediatric patients appear to be relatively spared. Recent cancer treatment does not appear to significantly increase the risk of death

Anti-α-gliadin antibodies (AGA) in the serum of coeliac children and controls recognize an identical collection of linear epitopes of α-gliadin

Anti-gliadin antibodies can be found in the serum of patients with overt and subclinical coeliac disease, but also in that of some controls. The aim of the present study was to identify the linear epitopes of the α-gliadin molecule to which the humoral response is directed. Therefore, the IgG and IgA antibody reactivity against an overlapping set of synthetic peptides covering the entire sequence of α-gliadin was measured in the sera from patients with coeliac disease, from controls with elevated titres of anti-gliadin antibodies and from healthy children using an ELISA technique. The antibodies mainly recognize peptides derived from the N-terminal region of α-gliadin, containing the motif QPFXXQXPY. Reactivity was also detected against two other synthetic peptides, which do not contain this motif and represent a sequence encoded further to the C-terminal region of α-gliadin. Anti-gliadin antibodies in sera from patients with coeliac disease and from controls recognize the same linear epitopes. Thus, serological investigation of the specificity of these antibodies using a peptide ELISA does not allow discrimination between patients and controls