Abstract only Introduction: The association between CAD severity and long-term outcomes in patients admitted with acute HF has not been determined. We characterized the angiographic burden of CAD in ...patients with acute HF and determined the association between CAD severity and mortality and readmission outcomes. Methods: In a multicenter registry of 70 hospitals in Ontario, Canada, we identified acute HF patients who underwent coronary angiography within 14 days of hospitalization (April 2010-March 2013) using stratified random sampling. We selected a cohort of HF patients with a higher a priori risk of CAD, defined inclusively as those with at least one of the following features: previous myocardial infarction (MI), troponin elevation, or angina on presentation. Using angiographic data, we defined obstructive CAD as the presence of > 70% stenosis in at least one epicardial vessel or > 50% left main (LM) stenosis. Multivessel disease (MVD) was defined as the presence of obstructive disease in 2 or more vessels. We determined adjusted associations between coronary anatomy and the rate of cardiovascular (CV) death and readmissions over two years. Results: Of 1772 patients undergoing angiography who met inclusion criteria (median age 71 IQR 62-79 years; 38.5% women), 1039 patients had CAD and 683 had MVD. Increasing CAD burden was associated with higher CV death (Figure). CV death was significantly increased in those with any CAD and HFpEF (HR 2.27, 95%CI; 1.12, 4.59, p=0.023). The rate of CV death was increased in MVD (HR 1.91, 95% CI; 1.32, 2.75, p<0.001) but not single-vessel disease (HR 1.15, 95%CI; 0.75, 1.77, p=0.516), compared to no obstructive CAD. There was no interaction between MVD and HFpEF or HFrEF status for the outcome of CV death (p=0.690). CV readmission was also significantly higher only in MVD (HR 1.28, 95%CI; 1.07, 1.54, p=0.008). Conclusion: In patients presenting with acute HF, angiographic MVD is associated with an increased rate of CV death and readmissions over 2 years.
While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As ...antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral “Fc fingerprint.” Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.
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•Beyond neutralization, antibodies drive antiviral control via Fc-mediated functions•Distinct vaccines elicit unique antibody Fc-effector profiles•Network analyses comprehensively integrating antibody profiles can compare vaccines•Case:control RV144 analysis points to mechanisms of reduced risk of HIV infection
Systems Serology reveals unique vaccine-induced “fingerprints,” highlighting potential markers of protection against HIV and providing a powerful method for comparing candidate vaccines against pathogens for which correlates of protection remain elusive.
Background & Aims Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and cost. Statistical analyses of the most recent data are necessary to guide GI research, education, ...and clinical practice. We estimate the burden of GI disease in the United States. Methods We collected information on the epidemiology of GI diseases (including cancers) and symptoms, along with data on resource utilization, quality of life, impairments to work and activity, morbidity, and mortality. These data were obtained from the National Ambulatory Medical Care Survey; National Health and Wellness Survey; Nationwide Inpatient Sample; Surveillance, Epidemiology, and End Results Program; National Vital Statistics System; Thompson Reuters MarketScan; Medicare; Medicaid; and the Clinical Outcomes Research Initiative's National Endoscopic Database. We estimated endoscopic use and costs and examined trends in endoscopic procedure. Results Abdominal pain was the most common GI symptom that prompted a clinic visit (15.9 million visits). Gastroesophageal reflux was the most common GI diagnosis (8.9 million visits). Hospitalizations and mortality from Clostridium difficile infection have doubled in the last 10 years. Acute pancreatitis was the most common reason for hospitalization (274,119 discharges). Colorectal cancer accounted for more than half of all GI cancers and was the leading cause of GI-related mortality (52,394 deaths). There were 6.9 million upper, 11.5 million lower, and 228,000 biliary endoscopies performed in 2009. The total cost for outpatient GI endoscopy examinations was $32.4 billion. Conclusions GI diseases are a source of substantial morbidity, mortality, and cost in the United States.
High-dose, posttransplantation cyclophosphamide (PTCy) reduces severe graft-versus-host disease (GVHD) after allogeneic blood or marrow transplantation (alloBMT), but the impact of PTCy on long-term, ...disease-specific outcomes is unclear. We conducted a retrospective study of 209 consecutive adult patients transplanted for acute myeloid leukemia (AML, n = 138), myelodysplastic syndrome (n = 28), or acute lymphoblastic leukemia (ALL, n = 43) using PTCy as sole GVHD prophylaxis after myeloablative conditioning and HLA-matched–related or –unrelated T-cell–replete allografting. At alloBMT, 30% of patients were not in morphologic complete remission. The cumulative incidences of grades II to IV and III to IV acute GVHD at 100 days and chronic GVHD at 2 years were 45%, 11%, and 13%, respectively. Forty-three percent of patients did not require immunosuppression for any reason beyond PTCy. At 3 years, relapse cumulative incidence was 36%, disease-free survival was 46%, survival free of disease and chronic GVHD was 39%, and overall survival was 58%. Lack of remission at alloBMT, adverse cytogenetics, and low allograft nucleated cell dose were associated with inferior survival for AML patients. Minimal residual disease but not t(9;22) was associated with inferior outcomes for ALL patients. The ability to limit posttransplantation immunosuppression makes PTCy a promising transplantation platform for the integration of postgrafting strategies to prevent relapse.
•Posttransplantation cyclophosphamide is effective as sole GVHD prophylaxis for myeloablative HLA-matched–related or –unrelated BMT.•Despite low chronic GVHD with PTCy, relapse and survival are comparable with outcomes reported using other GVHD prophylactic approaches.
IntroductionHip fractures are associated with a high burden of morbidity and mortality. Globally, there is wide variation in the incidence of hip fracture in people aged 50 years and older. ...Longitudinal and cross-geographical comparisons of health data can provide insights on aetiology, risk factors, and healthcare practices. However, systematic reviews of studies that use different methods and study periods do not permit direct comparison across geographical regions. Thus, the objective of this study is to investigate global secular trends in hip fracture incidence, mortality and use of postfracture pharmacological treatment across Asia, Oceania, North and South America, and Western and Northern Europe using a unified methodology applied to health records.Methods and analysisThis retrospective cohort study will use a common protocol and an analytical common data model approach to examine incidence of hip fracture across population-based databases in different geographical regions and healthcare settings. The study period will be from 2005 to 2018 subject to data availability in study sites. Patients aged 50 years and older and hospitalised due to hip fracture during the study period will be included. The primary outcome will be expressed as the annual incidence of hip fracture. Secondary outcomes will be the pharmacological treatment rate and mortality within 12 months following initial hip fracture by year. For the primary outcome, crude and standardised incidence of hip fracture will be reported. Linear regression will be used to test for time trends in the annual incidence. For secondary outcomes, the crude mortality and standardised mortality incidence will be reported.Ethics and disseminationEach participating site will follow the relevant local ethics and regulatory frameworks for study approval. The results of the study will be submitted for peer-reviewed scientific publications and presented at scientific conferences.
The impact of paravalvular regurgitation (PVR) following transcatheter aortic valve replacement (TAVR) remains uncertain. In this analysis, we sought to evaluate the impact of varying degrees of PVR ...on both mortality and changes in ventricular geometry and function.
Clinical and echocardiographic outcomes of patients who underwent TAVR from the randomized cohorts and continued access registries in the PARTNER trial were analysed after stratifying by severity of post-implant PVR, which was graded as none/trace in 52.9% (n = 1288), mild in 38.0% (n = 925), and moderate/severe in 9.1% (n = 221). There were significant differences in baseline clinical and echocardiographic characteristics. After TAVR, all the patients demonstrated increase in left ventricular (LV) function and reduction in the LV mass index, although the magnitude of mass regression was lower in the moderate/severe PVR group. The 30-day mortality (3.1 vs. 3.4 vs. 4.5%, P = 0.56) and stroke (3.4 vs. 3.7 vs. 2.3%, P = 0.59) were similar in all groups (none/trace, mild, and moderate/severe). At 1 year, there was increased all-cause mortality (15.9 vs. 22.2 vs. 35.1%, P < 0.0001), cardiac mortality (6.1 vs. 7.4% vs. 16.3%, P < 0.0001) and re-hospitalization (14.4 vs. 23.0 vs. 31.3%, P < 0.0001) with worsening PVR. A multivariable analysis indicated that the presence of moderate/severe PVR (HR: 2.18, 95% CI: 1.57-3.02, P < 0.0001) or mild PVR (HR: 1.37, 95% CI: 1.14-1.90, P = 0.012) was associated with higher late mortality.
Differences in baseline characteristics in patients with increasing severities of PVR may increase the risk of this complication. Despite these differences, multivariable analysis demonstrated that both mild and moderate/severe PVR predicted higher 1-year mortality.
Although Pentapetalae (comprising all core eudicots except Gunnerales) include almost equal to70% of all angiosperms, the origin of and relationships among the major lineages of this clade have ...remained largely unresolved. Phylogenetic analyses of 83 protein-coding and rRNA genes from the plastid genome for 86 species of seed plants, including new sequences from 25 eudicots, indicate that soon after its origin, Pentapetalae diverged into three clades: (i) a "superrosid" clade consisting of Rosidae, Vitaceae, and Saxifragales; (ii) a "superasterid" clade consisting of Berberidopsidales, Santalales, Caryophyllales, and Asteridae; and (iii) Dilleniaceae. Maximum-likelihood analyses support the position of Dilleniaceae as sister to superrosids, but topology tests did not reject alternative positions of Dilleniaceae as sister to Asteridae or all remaining Pentapetalae. Molecular dating analyses suggest that the major lineages within both superrosids and superasterids arose in as little as 5 million years. This phylogenetic hypothesis provides a crucial historical framework for future studies aimed at elucidating the underlying causes of the morphological and species diversity in Pentapetalae.
1 School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234, USA
2 Department of Veterinary Microbiology and Pathology, Washington State University Pullman, WA 99164-7040, ...USA
3 Washington State University Avian Health and Food Safety Laboratory, College of Veterinary Medicine, Washington State University, Puyallup, WA 98371-4998, USA
4 Department of Veterinary Microbiology and Pathology and Washington Animal Disease Diagnostic Laboratory, Washington State University Pullman, WA 99164-7040, USA
5 Franceschi Microscopy and Imaging Center, Washington State University, Pullman, WA 99164-4236, USA
Correspondence Michael E. Konkel konkel{at}wsu.edu
Campylobacter jejuni is a major food-borne bacterial pathogen, which is capable of causing diarrhoea containing blood and leukocytes. C. jejuni invasion of the intestinal epithelial cells and the release of proinflammatory molecules contribute to the pathophysiology of campylobacteriosis. Given the commensal relationship of C. jejuni with chickens, we hypothesized that C. jejuni invasion of chicken cells and the release of host cell cytokines would be significantly less than with human cells. To test our hypothesis, we examined the interactions of C. jejuni with chicken LMH cells, and performed in vivo experiments with chickens. The binding and internalization assays revealed that C. jejuni was significantly less invasive of LMH cells relative to human INT 407 cells, even though the bacteria bound to each host cell species equally. We also assessed interleukin-8 (IL-8) transcript, IL-8 secretion, and the release of chemoattractant molecules from the inoculated cells. Inoculation of LMH cells with C. jejuni stimulated expression of both chicken IL-8 orthologues, chCXCLi2 and chCXCLi1 , but at levels significantly less than human IL-8 ( huCXCL8 ) expressed from human INT 407 cells inoculated with C. jejuni . Moreover, the supernatant fluids of the C. jejuni- inoculated LMH cells resulted in little heterophil migration. In vivo , C. jejuni were observed bound to the cells lining the glandular crypts, but overt signs of cell invasion or pathology were not observed. These results indicate that cytokine expression in chicken LMH cells in response to C. jejuni is distinct from that of Salmonella typhimurium .
Abbreviations: C t , cycle threshold; IL-8, interleukin-8; p.i., post-inoculation; PMA/I, phorbol 12-myristate 13-acetate and ionomycin; TEM, transmission electron microscopy
IMPORTANCE: Lung cancer is the second most common cancer and the leading cause of cancer death in the US. In 2020, an estimated 228 820 persons were diagnosed with lung cancer, and 135 720 persons ...died of the disease. The most important risk factor for lung cancer is smoking. Increasing age is also a risk factor for lung cancer. Lung cancer has a generally poor prognosis, with an overall 5-year survival rate of 20.5%. However, early-stage lung cancer has a better prognosis and is more amenable to treatment. OBJECTIVE: To update its 2013 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the accuracy of screening for lung cancer with low-dose computed tomography (LDCT) and on the benefits and harms of screening for lung cancer and commissioned a collaborative modeling study to provide information about the optimum age at which to begin and end screening, the optimal screening interval, and the relative benefits and harms of different screening strategies compared with modified versions of multivariate risk prediction models. POPULATION: This recommendation statement applies to adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. EVIDENCE ASSESSMENT: The USPSTF concludes with moderate certainty that annual screening for lung cancer with LDCT has a moderate net benefit in persons at high risk of lung cancer based on age, total cumulative exposure to tobacco smoke, and years since quitting smoking. RECOMMENDATION: The USPSTF recommends annual screening for lung cancer with LDCT in adults aged 50 to 80 years who have a 20 pack-year smoking history and currently smoke or have quit within the past 15 years. Screening should be discontinued once a person has not smoked for 15 years or develops a health problem that substantially limits life expectancy or the ability or willingness to have curative lung surgery. (B recommendation) This recommendation replaces the 2013 USPSTF statement that recommended annual screening for lung cancer with LDCT in adults aged 55 to 80 years who have a 30 pack-year smoking history and currently smoke or have quit within the past 15 years.
Chicago's Array of Things (AoT) project is aptly described as a technology experiment or a “smart city” prototype. The concept of such an extensible “instrument” arose within a larger translational ...research vision applying computer science and engineering research for the multidimensional benefit of people and communities in cities. The AoT project hypothesized that wireless intelligent sensor networks could enable both quantitative social science and urban monitoring while also stimulating youth interest in science and technology. Successful deployment of such sensor networks could provide open data from urban measurements not only in support of diverse research questions—in environmental dynamics, urban architecture, engineering, and social sciences—but also informing community groups and city planners. The AoT project and its successor SAGE project are a computer science and engineering experiment, but its success is inextricably tied to community engagement and experiential education. Simply put, community acceptance is a prerequisite to installing and testing the instrument.
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