Emmanuel J. Favaloro

Bio: Emmanuel J. Favaloro is an academic researcher from Westmead Hospital. The author has contributed to research in topics: Von Willebrand disease & Von Willebrand factor. The author has an hindex of 60, co-authored 648 publications receiving 18261 citations. Previous affiliations of Emmanuel J. Favaloro include University of Verona & University of Sydney.

D-dimer is Associated with Severity of Coronavirus Disease 2019: A Pooled Analysis.

Abstract: A new infective outbreak, sustained by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined coronavirusdisease2019 (COVID-19), is nowspreadingall aroundthe world.1 The clinical course of this respiratory disease is complicated in up to 15% of infected patients by onset of interstitial pneumonia, evolving toward acute respiratory distress syndrome needing mechanical ventilation or admission to the intensive care unit (ICU), and is also often accompanied by multiorgan failure.2 Since there is now incontrovertible evidence that laboratory hemostasisprovides an essential contribution to decision-making and care of the vastmajorityofhumanpathologies,3weaimed to explorehere whether increased D-dimer values—which are a frequent occurrence in patients with COVID-194—may be associated with disease severity. An electronic search was performed in Medline (PubMed interface), Scopus, and Web of Science, using the keywords “laboratory” and “COVID-19” or “coronavirus 2019” or “2019nCoV” or “SARS-CoV-2,” between 2019 and present time (i.e., March 4, 2020),withno language restriction. The title, abstract, and full text of all documents that could be identified based on these search criteria were analyzed, and those reporting information on the difference of D-dimer values between COVID-19 patients with or without severe disease (i.e., those needing mechanicalventilation, ICUadmission,or thosewhodied)were finally included in our analysis. The reference list of each identified document was also examined for identifying additional eligible studies. A pooled analysiswasfinally performed, with calculation of weightedmean difference (WMD) and 95% confidence interval (CI) of D-dimer values between COVID-19 patientswithorwithout severedisease, usingMetaXL software Version 5.3 (EpiGear International Pty Ltd., Sunrise Beach, Australia). Mean and standard deviation were extrapolated from sample size, median, and interquartile range (IQR), according to Hozo et al.5 The study was performed in accordance with the Declaration of Helsinki and with the term of local legislation. Overall, 80 documents could be initially identifiedbasedon our search criteria, 77ofwhich ought to be excluded after title, abstract, or full text reading; since they were review articles (n1⁄4 6), commentaries, or other editorialmaterial (n1⁄4 1), they did not deal with COVID-19 disease (n1⁄4 62), or did not expressly reported the difference of D-dimer values in COVID-19 patients with or without severe disease (n1⁄4 8). One additional studycouldbe identified fromthe reference list of selected articles and another one was published while the articlewasunder revision so that a total number offive studies could finally be included in our analysis.6–10 Four of these five studies reported median and IQR values of D-dimer,6–9 while the remaining only showed the proportion of patientswith Ddimer values above the locally defined diagnostic cut-off.9 In the first study, Huang et al reported clinical and laboratory data of 41 patients hospitalized with laboratory-confirmed COVID-196 and observed that D-dimer values were nearly fivefold higher in those with severe disease (median: 2.4mg/L; IQR: 0.6–14.4mg/L) than in those without (median: 0.5mg/L; IQR: 0.3–0.8mg/L; p1⁄4 0.004). Tang et al also studied 183 patients with COVID-197 and found that D-dimer values were nearly 3.5-fold higher in those with severe disease (median: 2.12mg/L; IQR: 0.77–5.27mg/L) than in those without (median: 0.61mg/L; IQR: 0.35–1.29mg/L; p< 0.001). In the third study, published by Wang et al and including 138 patients hospitalized for COVID-19,8 D-dimer values were nearly 2.5-fold higher inpatientswith severedisease (median: 4.14mg/L; IQR: 1.91–13.2mg/L) than in thosewithout (median: 1.66mg/L; IQR: 1.01–2.85mg/L; p< 0.001). In the third study, Zhou et al studied 191 patients with COVID-199 and found that D-dimer values were nearly ninefold higher in

Characterization of GMP-140 (P-selectin) as a circulating plasma protein.

Abstract: GMP-140 is a 140-kD granule membrane protein, found in the alpha granules of platelets and the Weibel-Palade bodies of endothelial cells, that is surface expressed on cell activation and mediates neutrophil attachment. Cloning data for GMP-140 from an endothelial library predict a soluble form of the protein, the transcription message for which is also found in platelets. In this study, we report the detection by enzyme-linked immunosorbent assay of soluble GMP-140 in plasma centrifuged for 3 h at 100,000 g (to remove platelet microparticles) and confirm its identity by purification from plasma. Plasma concentrations were found to be 0.251 +/- 0.043 micrograms/ml (means +/- SD, n = 10) in normal male controls and 0.175 +/- 0.063 micrograms/ml (means +/- SD, n = 10) in normal female controls. The purified protein had an identical molecular mass (nonreduced) to platelet membrane GMP-140 (approximately 3 kD lower, reduced) and was immunoblotted by polyclonal anti-GMP-140, and the anti-GMP-140 monoclonal antibodies AK4 and AK6. Analytical gel filtration studies indicated that the plasma GMP-140 eluted as a monomer whereas detergent-free, platelet membrane GMP-140 eluted as a tetramer consistent with plasma GMP-140 lacking a transmembrane domain. Purified plasma GMP-140 bound to the same neutrophil receptor as the membrane-bound form, and when immobilized on plastic, bound neutrophils equivalently to immobilized platelet membrane GMP-140. Since it has been shown that fluid-phase GMP-140 is antiinflammatory and downregulates CD18-dependent neutrophil adhesion and respiratory burst, its presence in plasma may be of major importance in preventing the inadvertent activation of neutrophils in the circulation.

Standards of Medical Care in Diabetes

Abstract: XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.