Acute hypertension during cardiac surgery can be difficult to manage and may adversely affect patient outcomes. Clevidipine is a novel, rapidly acting dihydropyridine L-type calcium channel blocker ...with an ultrashort half-life that decreases arterial blood pressure (BP). The Evaluation of CLevidipine In the Perioperative Treatment of Hypertension Assessing Safety Events trial (ECLIPSE) was performed to compare the safety and efficacy of clevidipine (CLV) with nitroglycerin (NTG), sodium nitroprusside (SNP), and nicardipine (NIC) in the treatment of perioperative acute hypertension in patients undergoing cardiac surgery.
We analyzed data from three prospective, randomized, open-label, parallel comparison studies of CLV to NTG or SNP perioperatively, or NIC postoperatively in patients undergoing cardiac surgery at 61 medical centers. Of the 1964 patients enrolled, 1512 met postrandomization inclusion criteria of requiring acute treatment of hypertension based on clinical criteria. The patients were randomized 1:1 for each of the three parallel comparator treatment groups. The primary outcome was the incidence of death, myocardial infarction, stroke or renal dysfunction at 30 days. Adequacy and precision of BP control was evaluated and is reported as a secondary outcome.
There was no difference in the incidence of myocardial infarction, stroke or renal dysfunction for CLV-treated patients compared with the other treatment groups. There was no difference in mortality rates between the CLV, NTG or NIC groups. Mortality was significantly higher, though, for SNP-treated patients compared with CLV-treated patients (P=0.04). CLV was more effective compared with NTG (P=0.0006) or SNP (P=0.003) in maintaining BP within the prespecified BP range. CLV was equivalent to NIC in keeping patients within a prespecified BP range; however, when BP range was narrowed, CLV was associated with fewer BP excursions beyond these BP limits compared with NIC.
CLV is a safe and effective treatment for acute hypertension in patients undergoing cardiac surgery.
With the authors' metropolitan area rates for ACS admissions as the response variable, simple regressions using various measures of the evenness of distribution of African American populations within ...metropolitan areas as the explanatory variable show strong associations. T.A. LaVeist, "Segregation, Poverty, and Empowerment: Health Consequences for African Ameri- cans," Milbank Quarterly 71, no. 1 (1993): 41-64; A.P. Poledňák, "Poverty, Residential Segregation, and Black/White Mortality Ratios in Urban Areas," Journal of Health Care for the Poor and Underserved 4, no. 4 (1993): 363-373; and A.P. Poledňák, "Black-White Differences in Infant Mortality in Thirty-eight Standard Metropolitan Statistical Areas," American Journal of Public Health 81, no. 11 (1991): 1480-1482. ...in analytical work not reported in our paper, we have regressed ACS admission rates on both poverty and racial composition measures at the ZIP code level and found that although the proportion of minorities in an area's population adds some independent explanatory power, the proportion of persons in poverty remains a stronger predictor of ACS admission rates for most areas.
Abstract
In 2021 May, the Dark Energy Spectroscopic Instrument (DESI) began a 5 yr survey of approximately 50 million total extragalactic and Galactic targets. The primary DESI dark-time targets are ...emission line galaxies, luminous red galaxies, and quasars. In bright time, DESI will focus on two surveys known as the Bright Galaxy Survey and the Milky Way Survey. DESI also observes a selection of “secondary” targets for bespoke science goals. This paper gives an overview of the publicly available pipeline (
desitarget
) used to process targets for DESI observations. Highlights include details of the different DESI survey targeting phases, the targeting ID (
TARGETID
) used to define unique targets, the bitmasks used to indicate a particular type of target, the data model and structure of DESI targeting files, and examples of how to access and use the
desitarget
code base. This paper will also describe “supporting” DESI target classes, such as standard stars, sky locations, and random catalogs that mimic the angular selection function of DESI targets. The DESI target-selection pipeline is complex and sizable; this paper attempts to summarize the most salient information required to understand and work with DESI targeting data.
Coronavirus vaccines that are highly effective against current and anticipated SARS-CoV-2 variants are needed to control COVID-19. We previously reported a receptor-binding domain (RBD)-sortase ...A-conjugated ferritin nanoparticle (scNP) vaccine that induced neutralizing antibodies against SARS-CoV-2 and pre-emergent sarbecoviruses and protected non-human primates (NHPs) from SARS-CoV-2 WA-1 infection. Here, we find the RBD-scNP induced neutralizing antibodies in NHPs against pseudoviruses of SARS-CoV and SARS-CoV-2 variants including 614G, Beta, Delta, Omicron BA.1, BA.2, BA.2.12.1, and BA.4/BA.5, and a designed variant with escape mutations, PMS20. Adjuvant studies demonstrate variant neutralization titers are highest with 3M-052-aqueous formulation (AF). Immunization twice with RBD-scNPs protect NHPs from SARS-CoV-2 WA-1, Beta, and Delta variant challenge, and protect mice from challenges of SARS-CoV-2 Beta variant and two other heterologous sarbecoviruses. These results demonstrate the ability of RBD-scNPs to induce broad neutralization of SARS-CoV-2 variants and to protect animals from multiple different SARS-related viruses. Such a vaccine could provide broad immunity to SARS-CoV-2 variants.
The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would ...be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VHDJH) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs VH chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show that Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate that V1V2-glycan bnAbs are more readily induced than CD4bs bnAbs, and define VH replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.
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•HIV-1 vaccine-induced broadly neutralizing antibodies targeted the V1V2-glycan site•V1V2-glycan antibodies arose when host factors limited CD4 binding site antibodies•V-region secondary rearrangement was a mechanism for generating V1V2-glycan antibodies
Saunders et al. demonstrate that HIV-1 broadly neutralizing antibodies can be induced by vaccination, albeit only in select animals. Studies in neutralizing antibody variable heavy chain (VH) knockin mice suggest a mechanism for broadly neutralizing antibody induction that involves heavy chain replacement and fusion of immunoglobulin diversity (D) regions.
Candida Urinary Tract Infection: Pathogenesis Fisher, John F.; Kavanagh, Kevin; Sobel, Jack D. ...
Clinical infectious diseases,
05/2011, Letnik:
52, Številka:
suppl_6
Journal Article
Recenzirano
Odprti dostop
Candida species are unusual causes of urinary tract infection (UTI) in healthy individuals, but common in the hospital setting or among patients with predisposing diseases and structural ...abnormalities of the kidney and collecting system. The urinary tract may be invaded in either an antegrade fashion from the bloodstream or retrograde via the urethra and bladder. Candida species employ a repertoire of virulence factors, including phenotypic switching, dimorphism, galvano - and thigmotropism, and hydrolytic enzymes, to colonize and then invade the urinary tract. Antegrade infection occurs primarily among patients predisposed to candidemia. The process of adherence to and invasion of the glomerulus, renal blood vessels, and renal tubules by Candida species was elegantly described in early histopathologic studies. Armed with modern molecular biologic techniques, the various virulence factors involved in bloodborne infection of the kidney are gradually being elucidated. Disturbances of urine flow, whether congenital or acquired, instrumentation of the urinary tract, diabetes mellitus, antimicrobial therapy, and immunosuppression underlie most instances of retrograde Candida UTI. In addition, bacterial UTIs caused by Enterobacteriaceae may facilitate the initial step in the process. Ascending infections generally do not result in candidemia in the absence of obstruction.
Simple, reliable measures of the quality of the environment in which a child was reared that can be used in clinical research and practice are lacking.
The reliability and validity of a global scale ...to retrospectively appraise the quality of that environment were examined. Fifty-three clinicians from 4 centers in Australia and 1 in Hong Kong, People's Republic of China, used the scale to rate 7 case vignettes; 4 clinicians rated 20 medical records, and 49 rated 211 subjects after clinical interviews.
Interrater reliability (intraclass correlation coefficient) was 0.82 (time 1) and 0.84 (time 2) for case vignettes, 0.90 for medical records, and 0.89 for clinical interviews. Consistency in time was high (r = 0.91). Lower ratings, indicative of a less adequate environment, were associated with a clinical diagnosis of oppositional defiant or conduct disorder.
Our simple-to-use scale appears to measure reliably a relevant clinical construct and fills a gap among the instruments available. Ratings may be useful as a cost-effective index to consider in outcome studies, when examining response to treatment, or in other clinical research.
Risk stratifying patients with cardiogenic shock (CS) is a major unmet need. The recently proposed Society for Cardiovascular Angiography and Interventions (SCAI) stages as an approach to identify ...patients at risk for in-hospital mortality remains under investigation. We studied the utility of the SCAI stages and further explored the impact of hemodynamic congestion on clinical outcomes.
The CS Working Group registry includes patients with CS from 8 medical centers enrolled between 2016 and 2019. Patients were classified by the maximum SCAI stage (B-E) reached during their hospital stay according to drug and device utilization. In-hospital mortality was evaluated for association with SCAI stages and hemodynamic congestion.
Of the 1414 patients with CS, the majority were due to decompensated heart failure (50%) or myocardial infarction (MI; 35%). In-hospital mortality was 31% for the total cohort, but higher among patients with MI (41% versus 26%, MI versus heart failure,
<0.0001). Risk for in-hospital mortality was associated with increasing SCAI stage (odds ratio 95% CI, 3.25 2.63-4.02) in both MI and heart failure cohorts. Hemodynamic data was available in 1116 (79%) patients. Elevated biventricular filling pressures were common among patients with CS, and right atrial pressure was associated with increased mortality and higher SCAI Stage.
Our findings support an association between the proposed SCAI staging system and in-hospital mortality among patient with heart failure and MI. We further identify that venous congestion is common and identifies patients with CS at high risk for in-hospital mortality. These findings provide may inform future management protocols and clinical studies.
Nonmydriatic fundus photography by non-ophthalmic-trained personnel has recently been shown to be a potential alternative to direct ophthalmoscopy in the emergency department (ED). We evaluated the ...reliability of a novel quality rating scale and applied this scale to nonmydriatic fundus photographs taken during routine ED patient encounters to determine factors associated with diminished photograph quality.
Prospective, cross-sectional study.
We included 350 patients enrolled in the Fundus photography versus Ophthalmoscopy Trials Outcomes in the Emergency Department study who were photographed by nurse practitioners after <30 minutes of training followed by supervision.
Photographs of both eyes were graded for quality on 2 occasions by 2 neuro-ophthalmologists. Four regions were independently evaluated for quality: Optic disc, macula, and superior and inferior vascular arcades. Quality as a function of the number of photographs taken was evaluated by Kaplan-Meier analysis. Mixed effects ordinal logistic regression was used to evaluate for predictors of image quality while accounting for the repeated measures design.
Overall photographic quality (1-5 scale; 5 best).
We evaluated 1734 photographs. Inter- and intraobserver agreements between neuro-ophthalmologists were very good (weighted kappa, 0.84-0.87). Quality of the optic disc area was better than those of other retinal areas (P<0.002). Kaplan-Meier analysis showed that if a high-quality photograph of an eye was not obtained by the third attempt, it was unlikely that one would be obtained at all. A 10-second increase in the interphotograph interval before a total of 40 seconds increased the odds of a 1-unit higher quality rating by 1.81 times (95% confidence interval CI, 1.68-1.98), and a 10-year increase in age decreased the odds by 0.76 times (95% CI, 0.69-0.85). Black patients had 0.42 times (95% CI, 0.28-0.63) the odds of a 1-unit higher quality rating compared with whites.
Our 5-point scale is a reliable measure of nonmydriatic photograph quality. The region of interest, interphotograph interval, and patient age and race are significant predictors of image quality for nonmydriatic photographs taken by nurse practitioners in the ED. Addressing these factors may have a direct impact on the successful implementation of nonmydriatic fundus photography into the ED.
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