Epidemiology and clinical course of severe acute respiratory syndrome coronavirus 2 infection in cancer patients in the Veneto Oncology Network: The Rete Oncologica Veneta covID19 study

Introduction: Coronavirus disease 2019 (COVID-19) pandemic started in Italy with clusters identified in Northern Italy. The Veneto Oncology Network (Rete Oncologica Veneta) licenced dedicated guidelines to ensure proper care minimising the risk of infection in patients with cancer. Rete Oncologica Veneta covID19 (ROVID) is a regional registry aimed at describing epidemiology and clinical course of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with cancer. Materials and methods: Patients with cancer diagnosis and documented SARS-CoV-2 infection are eligible. Data on cancer diagnosis, comorbidities, anticancer treatments, as well as details on SARS-CoV-2 infection (hospitalisation, treatments, fate of the infection), have been recorded. Logistic regression analysis was applied to calculate the association between clinical/laboratory variables and death from any cause. Results: One hundred seventy patients have been enrolled. The median age at time of the SARS-CoV infection was 70 years (25-92). The most common cancer type was breast cancer (n = 40). The majority of the patients had stage IV disease. Half of the patients had two or more comorbidities. The majority of the patients (78%) presented with COVID-19 symptoms. More than 77% of the patients were hospitalized and 6% were admitted to intensive care units. Overall, 104 patients have documented resolution of the infection. Fifty-seven patients (33%) have died. In 29 cases (17%), the cause of death was directly correlated to SARS-CoV-2 infection. Factors significantly correlated with the risk of death were the following: Eastern Cooperative Oncology Group performance status (PS), age, presence of two or more comorbidities, presence of dyspnoea, COVID-19 phenotype ≥ 3, hospitalisation, intensive care unit admission, neutrophil/lymphocyte ratio and thrombocytopenia. Conclusions: The mortality rate reported in this confirms the frailty of this population. These data reinforce the need to protect patients with cancer from SARS-CoV-2 infection

Sub-Femto- g Free Fall for Space-Based Gravitational Wave Observatories: LISA Pathfinder Results

We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1  fm s−2/Hz, or (0.54±0.01)×10−15  g/Hz, with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3)  fm/Hz, about 2 orders of magnitude better than requirements. At f≤0.5  mHz we observe a low-frequency tail that stays below 12  fm s−2/Hz down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.CNES 1316634/CNRS 103747UnivEarthS Labex program/ANR-10-LABX-0023UnivEarthS Labex program/ANR-11-IDEX-0005-02DLRFederal Ministry for Economic Affairs and Energy/FKZ 50OQ0501Federal Ministry for Economic Affairs and Energy/FKZ 50OQ1601Agenzia Spaziale ItalianaInstituto Nazionale di Fisica NucleareAYA2010-15709 (MICINN)ESP2013-47637-P (MINECO)ESP2015-67234-P (MINECO)Fundacion General CSICSwiss Space Office (SSO)Swiss National Science FoundationUnited Kingdom Space Agency (UKSA)University of GlasgowUniversity of BirminghamImperial CollegeScottish Universities Physics Alliance (SUPA)U.S. National Aeronautics and Space Administration (NASA

Role of blood cells dynamism on hemostatic complications in low-risk patients with essential thrombocythemia

Patients with essential thrombocythemia (ET) aged less than 60 years, who have not suffered a previous vascular event (low-risk patients), may develop thrombotic or hemorrhagic events. So far, it has not been possible to identify useful markers capable of predicting which of these patients are more likely to develop an event and therefore who needs to be treated. In the present study, we analysed the relationship between vascular complications and longitudinal blood counts of 136 low-risk ET patients taken over a sustained period of time (blood cells dynamism). After a median follow-up of 60 months, 45 out of 136 patients (33%) suffered 40 major thrombotic and 5 severe hemorrhagic complications. A total number of 5,781 blood counts were collected longitudinally. Thrombotic and hemorrhagic events were studied together (primary endpoint) but also separately (thrombotic alone = secondary endpoint; hemorrhagic alone = tertiary endpoint). The primary endpoint showed no significant association between platelet and WBC count at diagnosis and risk of any event (platelet, p = 0.797; WBC, p = 0.178), while Hb at baseline did show an association (p = 0.024). In the dynamic analysis with Cox regression model, where the blood count values were studied by time of follow-up, we observed that the risk for Hb was 1.49 (95% CI 1.13-1.97) for every increase of 1 g/dL, and that this risk then marginally decreased during follow-up. WBC was associated with an increased risk at baseline for every increase of 1 7 10(9)/L (hazard ratio (HR) 1.07, 95% CI 1.01-1.13, p = 0.034), the risk was stable during follow-up (HR 0.95, p = 0.187 at 60 months). Also, for each increment at baseline of 100 7 10(9) platelets/L, HR was increased by 1.08 (95% CI 0.97-1.22, p = 0.159) and decreases during follow-up. In conclusion, this study is the first to evaluate in ET low-risk patients, the risk of developing a thrombotic/hemorrhagic event considering blood counts over time. Overall our study shows that the risk changes over time. For example, the risk associated with WCC is not linear as previously reported. An interesting new finding is that PLT and even Hb contribute to the risk of developing vascular events. Future treatments should take into consideration these findings and aim to control all parameters over time. We believe this early study may help develop a dynamic analysis model to predict thrombosis in the single patient. Further studies are now warranted to further validate our findings

Cytogenetic and Molecular Predictors of Outcome in Acute Lymphocytic Leukemia: Recent Developments

During the last decade a tremendous technologic progress based on genome-wide profiling of genetic aberrations, structural DNA alterations, and sequence variations has allowed a better understanding of the molecular basis of pediatric and adult B/T- acute lymphoblastic leukemia (ALL), contributing to a better recognition of the biological heterogeneity of ALL and to a more precise definition of risk factors. Importantly, these advances identified novel potential targets for therapeutic intervention. This review will be focused on the cytogenetic/molecular advances in pediatric and adult ALL based on recently published articles

MODERN IMMUNOTHERAPY OF ADULT B-LINEAGE ACUTE LYMPHOBLASTIC LEUKEMIA WITH MONOCLONAL ANTIBODIES AND CHIMERIC ANTIGEN RECEPTOR MODIFIED T CELLS

The introduction of newer cytotoxic monoclonal antibodies and the chimeric antigen receptor-modified T-cells is opening a new age in the management of B-lineage adult acute lymphoblastic leukemia. This therapeutic change must be very positively acknowledged because of the limits of intensive chemotherapy programs and allogeneic stem cell transplantation. With these traditional therapeutic tools in fact cure can be achieve in only 40-50% of the patients, with higher failure rates in the elderly, in those with post-induction persistence of minimal residual disease and especially in refractory/relapsed disease. The place of the novel immunotherapeutics in improving the outcome of adult patients with B-lineage acute lymphoblastic leukemia is reviewed

Assessing the performance of new chromatographic technologies for the separation of peptide epimeric impurities: the case of Icatibant

: The biopharmaceutical industry faces the challenge of efficiently characterising impurity profiles of therapeutical peptides, also due to their complex polar and ionisable attributes. This research explores the potential of advanced chromatographic techniques to address this challenge. The study compares dynamic electrostatic repulsion reversed phase (d-ERRP) to its counterparts (static ERRP and ion pair reversed phase IP-RP) in analysing Icatibant and its elusive epimeric impurity, [L-Arg]1-Icatibant and highlights its exceptional capabilities in generating symmetric peaks, mitigating the common tailing phenomenon, and serving as a steadfast guardian of column longevity. The result highlights d-ERRP as a pioneering tool in the domain of liquid chromatography, fostering its role as a reference technique for the analysis of therapeutic peptides

Controle da infecção por Salmonella Enteritidis em frangos de corte com ácidos orgânicos e mananoligossacarídeo Control of the infection caused by Salmonella Enteritidis with organic acids and mannanoligosaccharide in broiler

O objetivo deste estudo foi avaliar a ação de dois ácidos orgânicos (ácido fórmico e ácido propiônico) e de um mananoligossacarídeo (MOS) adicionados à dieta no controle da infecção intestinal por Salmonella Enteritidis (SE) em frangos de corte. Neste estudo de 39 dias, foram utilizadas 150 aves, de um dia de idade, da linhagem Cobb, lote misto, livre de SE, divididas em seis tratamentos (T) com 25 animais cada, em que: T1 (ausência de infecção), T2 (ácidos orgânicos e ausência de infecção), T3 (ácidos orgânicos + MOS e ausência de infecção), T4 (ácidos orgânicos e infecção com SE), T5 (ácidos orgânicos + MOS e infecção com SE) e T6 (infecção com SE). No 4° dia após o alojamento, a cama foi instilada com SE e a cada sete dias cinco aves por grupo foram submetidas à eutanásia por deslocamento cervical e necropsiadas. Depois foram realizados exames bacteriológicos para SE nesses animais, utilizando fezes coletadas sobre a cama de maravalha dos grupos e das tonsilas cecais dos animais necropsiados. No 18° dia, somente 60% das aves estavam infectadas nos tratamentos T4 e T5; no 25° dia, 40% das aves no T4 e 20% no T5 estavam infectadas; no 32° dia 100% das amostras testadas foram negativas em ambos os tratamentos (T4 e T5). Constatou-se que o T6 foi 100% positivo até o 32° dia e no 39° dia reduziu em 20% o número de animais infectados. Dentro dos parâmetros de avaliação deste experimento, os ácidos orgânicos e o mananoligossacarídeo adicionados à dieta contribuíram para o controle da infecção por SE.The objective of this study was to evaluate the effect of two organic acids (formic acid and propionic acid) and of one mannanoligosaccharide added to the diet to control the intestinal infection caused by Salmonella Enteritidis (SE) in broilers. In this study of 39 days 150 birds were used, with one day of age, of the Cobb lineage, both sexes and free of SE. They were divided in 6 different treatments (T) with 25 birds each, where: T1 (no infection), T2 (organic acids + no infection), T3 (organic acids + mannanoligosaccharide and no infection), T4 (organic acids and infection with SE) T5 (organic acids + mannanoligosaccharide + and infection with SE) T6 (infection with SE). After housing, the chicken litter was instilled on the 4th day with SE and every seven days, five birds from each group were euthanized through cervical dislocation. The necropsy was performed and also the bacteriological exams to detect SE, using the feces collected over the chicken litter of the groups, bacteriological analysis of the cecal tonsils was done as well. On the 18th day only 60% of birds were infected in treatments T4 and T5; on the 25th day, 40% of birds in T4 and 20% in the T5 were infected; on the 32nd day, 100% of tested samples were negative in both treatments. The T6 group was 100% positive until the 32nd day, but on the 39th day, it got reduced in 20% of the number of infected animals. In the experimental conditions of this study, the organic acids and the mannanoligosaccharide added to the diet contributed to control the infection caused by SE

Expanding the Use of Dynamic Electrostatic Repulsion Reversed-Phase Chromatography: An Effective Elution Mode for Peptides Control and Analysis

Bioactive peptides are increasingly used in clinical practice. Reversed-phase chromatography using formic or trifluoroacetic acid in the mobile phase is the most widely used technique for their analytical control. However, sometimes it does not prove sufficient to solve challenging chromatographic problems. In the search for alternative elution modes, the dynamic electrostatic repulsion reversed-phase was evaluated to separate eight probe peptides characterised by different molecular weights and isoelectric points. This technique, which involves TBAHSO4 in the mobile phase, provided the lowest asymmetry and peak width at half height values and the highest in peak capacity (about 200 for a gradient of 30 min) and resolution concerning the classic reversed-phase. All analyses were performed using cutting-edge columns developed for peptide separation, and the comparison of the chromatograms obtained shows how the dynamic electrostatic repulsion reversed-phase is an attractive alternative to the classic reversed-phase