Venous thromboembolism in critically ill patients with pneumonia in the pre-COVID-19 era: Data from a large public database

Background The magnitude of venous thromboembolism (VTE) risk in severe COVID-19 is a matter of debate because of study heterogeneity, changes in VTE management, and scarce evidence of VTE risk in critically ill patients with pneumonia in the pre-COVID-19 era. Objectives To evaluate VTE risk in the pre-COVID-19 era in a large intensive care unit (ICU) database. Patients/Methods Data from consecutive pneumonia patients admitted to the ICU were retrieved from the Medical Information Mart for Intensive Care III. VTE risk was described in the entire cohort and in subgroups. Results Among 6842 pneumonia patients admitted to the ICU, 486 patients were diagnosed with VTE after a median of 3 (IQR 1-11) days in the ICU. The 30-day cumulative incidence of VTE was 7% and remained at this level across different age groups, sex, and type of ICU. After adjusting for death, the overall cumulative incidence of VTE was 5%. A total of 1788 patients received thromboprophylaxis (of 2958 for whom that data were available). VTE occurred in 10.7% (95% CI 9.0-12.6) of patients without thromboprophylaxis and in 6.4% (95% CI 5.4-7.6) of those with thromboprophylaxis. Mortality was 20.6% among patients with VTE and 19.2% among those without VTE. Conclusions In the pre-COVID-19 era, VTE risk in ICU patients with pneumonia was high and decreased with thromboprophylaxis. These findings can serve as comparators for future studies aiming at evaluating the impact of COVID-19 or other emerging infections on VTE risk

Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study

<p>Abstract</p> <p>Background</p> <p>Septic shock is the most feared complication of chemotherapy-induced febrile neutropenia. So far, there are no robust biomarkers that can stratify patients to the risk of sepsis complications. The VEGF-A axis is involved in the control of microvascular permeability and has been involved in the pathogenesis of conditions associated with endothelial barrier disruption such as sepsis. sFlt-1 is a soluble variant of the VEGF-A receptor VEGFR-1 that acts as a decoy receptor down-regulating the effects of VEGF-A. In animal models of sepsis, sFlt-1 was capable to block the barrier-breaking negative effects of VEGF-A and to significantly decrease mortality. In non-neutropenic patients, sFlt-1 has been shown to be a promising biomarker for sepsis severity.</p> <p>Methods</p> <p>We prospectively evaluated concentrations of sFlt-1 and VEGF-A at different time-points during febrile neutropenia, and evaluated the association of these levels with sepsis severity and septic shock development.</p> <p>Results</p> <p>Neutropenic patients that evolved with septic shock (n = 10) presented higher levels of sFlt-1 and VEGF-A measured 48 hours after fever onset than patients with non-complicated sepsis (n = 31) and levels of these biomarkers correlated with sepsis severity scores. Estimation of the diagnostic accuracy of sFlt-1 levels for the discrimination of patients that evolved to septic shock yielded promising results in our study population.</p> <p>Discussion</p> <p>Our data suggest that sFlt-1 and VEGF-A could be useful biomarkers for sepsis severity in patients with febrile neutropenia. In addition, the kinetics of sFlt-1 release in patients that evolve to septic shock suggest that the sFlt-1 could be a salvage compensatory mechanism in patients with septic shock, but that the magnitude of the sFlt-1 release observed in human sepsis is not sufficient to reproduce the beneficial anti-VEGF-A effects observed in animal models of sepsis.</p

Folate, Vitamin B12 And Homocysteine Status In The Post-folic Acid Fortification Era In Different Subgroups Of The Brazilian Population Attended To At A Public Health Care Center.

Folate and vitamin B12 are essential nutrients, whose deficiencies are considerable public health problems worldwide, affecting all age groups. Low levels of these vitamins have been associated with high concentrations of homocysteine (Hcy) and can lead to health complications. Several genetic polymorphisms affect the metabolism of these vitamins. The aims of this study were to assess folate, vitamin B12 and homocysteine status in distinct Brazilian individuals after the initiation of folic acid fortification by Brazilian authorities and to investigate the effects of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms on folate, vitamin B12 and Hcy levels in these populations. A total of 719 individuals including the elderly, children, as well as pregnant and lactating women were recruited from our health care center. Folate, vitamin B12 and Hcy levels were measured by conventional methods. Genotype analyses of RFC1 A80G, GCPII C1561T and MTHFR C677T polymorphisms were performed by PCR-RFLP. The overall prevalence of folate and vitamin B12 deficiencies were 0.3% and 4.9%, respectively. Folate deficiency was observed only in the elderly (0.4%) and pregnant women (0.3%), whereas vitamin B12 deficiency was observed mainly in pregnant women (7.9%) and the elderly (4.2%). Plasma Hcy concentrations were significantly higher in the elderly (33.6%). Pregnant women carrying the MTHFR 677TT genotype showed lower serum folate levels (p = 0.042) and higher Hcy levels (p = 0.003). RFC1 A80G and GCPII C1561T polymorphisms did not affect folate and Hcy levels in the study group. After a multivariate analysis, Hcy levels were predicted by variables such as folate, vitamin B12, gender, age and RFC1 A80G polymorphism, according to the groups studied. Our results suggest that folate deficiency is practically nonexistent in the post-folic acid fortification era in the subgroups evaluated. However, screening for vitamin B12 deficiency may be particularly relevant in our population, especially in the elderly.141

Prevalence of transfusion-transmitted Chagas disease among multitransfused patients in Brazil

<p>Abstract</p> <p>Background</p> <p>Blood transfusion has always been an important route for Chagas Disease (CD) transmission. The high prevalence of CD in Latin America and its lifelong asymptomatic clinical picture pose a threat for the safety of the blood supply. The outcome of measures designed to improve transfusion safety can be assessed by evaluating the prevalence of CD among multitransfused patients</p> <p>Methods</p> <p>In order to assess the impact of CD control measures on the safety of the blood supply, an observational cross-sectional study was designed to determine the prevalence of CD in 351 highly transfused patients, in which vectorial transmission was excluded. This study compared patients that received transfusion products before (n = 230) and after (n = 121) 1997, when measures to control transfusion-transmitted CD were fully implemented in Brazil.</p> <p>Results</p> <p>The study group consisted of 351 patients exposed to high numbers of blood products during their lifetime (median number of units transfused = 51, range 10–2086). A higher prevalence of transfusion-transmitted CD (1.30%) was observed among multitransfused patients that received their first transfusion before 1997, compared with no cases of transfusion-transmitted CD among multitransfused patients transfused after that year. The magnitude of the exposure to blood products was similar among both groups (mean number of units transfused per year of exposure = 25.00 ± 26.46 and 23.99 ± 30.58 respectively; P = 0.75, Mann-Whitney test).</p> <p>Conclusion</p> <p>Multiple initiatives aimed to control vector and parental transmission of CD can significantly decrease transfusion-transmitted CD in Brazil. Our data suggest that mandatory donor screening for CD represents the most important measure to interrupt transmission of CD by blood transfusions.</p

An update on the global use of risk assessment models and thromboprophylaxis in hospitalized patients with medical illnesses from the World Thrombosis Day steering committee: Systematic review and meta-analysis

INTRODUCTION Venous thromboembolism (VTE) is a leading cause of cardiovascular morbidity and mortality. The majority of VTE events are hospital-associated. In 2008, the Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting (ENDORSE) multinational cross-sectional study reported that only approximately 40% of medical patients at risk of VTE received adequate thromboprophylaxis. METHODS In our systematic review and meta-analysis, we aimed at providing updated figures concerning the use of thromboprophylaxis globally. We focused on: (a) the frequency of patients with an indication to thromboprophylaxis according with individual models; (b) the use of adequate thromboprophylaxis; and (c) reported contraindications to thromboprophylaxis. Observational nonrandomized studies or surveys focusing on medically ill patients were considered eligible. RESULTS After screening, we included 27 studies from 20 countries for a total of 137 288 patients. Overall, 50.5% (95% confidence interval [CI]: 41.9-59.1, I$^{2}$ 99%) of patients had an indication to thromboprophylaxis: of these, 54.5% (95% CI: 46.2-62.6, I$^{2}$ 99%) received adequate thromboprophylaxis. The use of adequate thromboprophylaxis was 66.8% in Europe (95% CI: 50.7-81.1, I$^{2}$ 98%), 44.9% in Africa (95% CI: 31.8-58.4, I$^{2}$ 96%), 37.6% in Asia (95% CI: 25.7-50.3, I$^{2}$ 97%), 58.3% in South America (95% CI: 31.1-83.1, I$^{2}$ 99%), and 68.6% in North America (95% CI: 64.9-72.6, I$^{2}$ 96%). No major differences in adequate thromboprophylaxis use were found across risk assessment models. Bleeding, thrombocytopenia, and renal/hepatic failure were the most frequently reported contraindications to thromboprophylaxis. CONCLUSIONS The use of anticoagulants for VTE prevention has been proven effective and safe, but thromboprophylaxis prescriptions are still unsatisfactory among hospitalized medically ill patients around the globe with marked geographical differences

Morphological and Transcriptional Changes in Human Bone Marrow During Natural Plasmodium vivax Malaria Infections.

--- - Label: BACKGROUND NlmCategory: BACKGROUND content: The presence of Plasmodium vivax malaria parasites in the human bone marrow (BM) is still controversial. However, recent data from a clinical case and experimental infections in splenectomized nonhuman primates unequivocally demonstrated the presence of parasites in this tissue. - Label: METHODS NlmCategory: METHODS content: In the current study, we analyzed BM aspirates of 7 patients during the acute attack and 42 days after drug treatment. RNA extracted from CD71+ cell suspensions was used for sequencing and transcriptomic analysis. - Label: RESULTS NlmCategory: RESULTS content: We demonstrated the presence of parasites in all patients during acute infections. To provide further insights, we purified CD71+ BM cells and demonstrated dyserythropoiesis and inefficient erythropoiesis in all patients. In addition, RNA sequencing from 3 patients showed that genes related to erythroid maturation were down-regulated during acute infections, whereas immune response genes were up-regulated. - Label: CONCLUSIONS NlmCategory: CONCLUSIONS content: This study thus shows that during P. vivax infections, parasites are always present in the BM and that such infections induced dyserythropoiesis and ineffective erythropoiesis. Moreover, infections induce transcriptional changes associated with such altered erythropoietic response, thus highlighting the importance of this hidden niche during natural infections

Imbalances in serum angiopoietin concentrations are early predictors of septic shock development in patients with post chemotherapy febrile neutropenia

Background: Febrile neutropenia carries a high risk of sepsis complications, and the identification of biomarkers capable to identify high risk patients is a great challenge. Angiopoietins (Ang -) are cytokines involved in the control microvascular permeability. It is accepted that Ang-1 expression maintains endothelial barrier integrity, and that Ang-2 acts as an antagonizing cytokine with barrier-disrupting functions in inflammatory situations. Ang-2 levels have been recently correlated with sepsis mortality in intensive care units. Methods: We prospectively evaluated concentrations of Ang-1 and Ang-2 at different time-points during febrile neutropenia, and explored the diagnostic accuracy of these mediators as potential predictors of poor outcome in this clinical setting before the development of sepsis complications. Results: Patients that evolved with septic shock (n = 10) presented higher levels of Ang-2 measured 48 hours after fever onset, and of the Ang-2/Ang-1 ratio at the time of fever onset compared to patients with non-complicated sepsis (n = 31). These levels correlated with sepsis severity scores. Conclusions: Our data suggest that imbalances in the concentrations of Ang-1 and Ang-2 are independent and early markers of the risk of developing septic shock and of sepsis mortality in febrile neutropenia, and larger studies are warranted to validate their clinical usefulness. Therapeutic strategies that manipulate this Ang-2/Ang-1 imbalance can potentially offer new and promising treatments for sepsis in febrile neutropenia

The era of reference genomes in conservation genomics

Progress in genome sequencing now enables the large-scale generation of reference genomes. Various international initiatives aim to generate reference genomes representing global biodiversity. These genomes provide unique insights into genomic diversity and architecture, thereby enabling comprehensive analyses of population and functional genomics, and are expected to revolutionize conservation genomics

The era of reference genomes in conservation genomics

Progress in genome sequencing now enables the large-scale generation of reference genomes. Various international initiatives aim to generate reference genomes representing global biodiversity. These genomes provide unique insights into genomic diversity and architecture, thereby enabling comprehensive analyses of population and functional genomics, and are expected to revolutionize conservation genomics