IMPORTANCE: Major postoperative complications and delirium contribute independently to adverse outcomes and high resource use in patients who undergo major surgery; however, their interrelationship ...is not well examined. OBJECTIVE: To evaluate the association of major postoperative complications and delirium, alone and combined, with adverse outcomes after surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study in 2 large academic medical centers of 566 patients who were 70 years or older without recognized dementia or a history of delirium and underwent elective major orthopedic, vascular, or abdominal surgical procedures with a minimum 3-day hospitalization between June 18, 2010, and August 8, 2013. Data analysis took place from December 13, 2013, through May 1, 2015. MAIN OUTCOMES AND MEASURES: Major postoperative complications, defined as life-altering or life-threatening events (Accordion Severity grade 2 or higher), were identified by expert-panel adjudication. Delirium was measured daily with the Confusion Assessment Method and a validated medical record review method. The following 4 subgroups were analyzed: (1) no complications or delirium; (2) complications only; (3) delirium only; and (4) complications and delirium. Adverse outcomes included a length of stay (LOS) of more than 5 days, institutional discharge, and rehospitalization within 30 days of discharge. RESULTS: In the 566 participants, the mean (SD) age was 76.7 (5.2) years, 236 (41.7%) were male, and 523 (92.4%) were white. Forty-seven patients (8.3%) developed major complications and 135 (23.9%) developed delirium. Compared with no complications or delirium as the reference group, major complications only contributed to prolonged LOS only (relative risk RR, 2.8; 95% CI, 1.9-4.0); by contrast, delirium only significantly increased all adverse outcomes, including prolonged LOS (RR, 1.9; 95% CI, 1.4-2.7), institutional discharge (RR, 1.5; 95% CI, 1.3-1.7), and 30-day readmission (RR, 2.3; 95% CI, 1.4-3.7). The subgroup with complications and delirium had the highest rates of all adverse outcomes, including prolonged LOS (RR, 3.4; 95% CI, 2.3-4.8), institutional discharge (RR, 1.8; 95% CI, 1.4-2.5), and 30-day readmission (RR, 3.0; 95% CI, 1.3-6.8). Delirium exerted the highest attributable risk at the population level (5.8%; 95% CI, 4.7-6.8) compared with all other adverse events (prolonged LOS, institutional discharge, or readmission). CONCLUSIONS AND RELEVANCE: Major postoperative complications and delirium are separately associated with adverse events and demonstrate a combined effect. Delirium occurs more frequently and has a greater effect at the population level than other major complications.
All coronaviruses known to have recently emerged as human pathogens probably originated in bats
. Here we use a single experimental platform based on immunodeficient mice implanted with human lung ...tissue (hereafter, human lung-only mice (LoM)) to demonstrate the efficient in vivo replication of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as well as two endogenous SARS-like bat coronaviruses that show potential for emergence as human pathogens. Virus replication in this model occurs in bona fide human lung tissue and does not require any type of adaptation of the virus or the host. Our results indicate that bats contain endogenous coronaviruses that are capable of direct transmission to humans. Our detailed analysis of in vivo infection with SARS-CoV-2 in human lung tissue from LoM showed a predominant infection of human lung epithelial cells, including type-2 pneumocytes that are present in alveoli and ciliated airway cells. Acute infection with SARS-CoV-2 was highly cytopathic and induced a robust and sustained type-I interferon and inflammatory cytokine and chemokine response. Finally, we evaluated a therapeutic and pre-exposure prophylaxis strategy for SARS-CoV-2 infection. Our results show that therapeutic and prophylactic administration of EIDD-2801-an oral broad-spectrum antiviral agent that is currently in phase II/III clinical trials-markedly inhibited SARS-CoV-2 replication in vivo, and thus has considerable potential for the prevention and treatment of COVID-19.
Background. The aim of this study was to determine the relationship between vasodilatation-induced ischemia and poststress glucose uptake. Coronary vasodilators may induce myocardial ischemia due to ...coronary steal through collateral circulation or transmural blood flow redistribution with diminished subendocardial perfusion. Myocardial ischemia can be demonstrated by increased glucose uptake as previously shown in patients with exercise-induced ischemia. Methods and Results. We studied 11 patients with single-vessel disease and no history of myocardial infarction. Five patients had no collateral circulation, and 6 had angiographic evidence of collateral vessels. We measured myocardial blood flow (MBF) and glucose uptake at baseline and after the administration of dipyridamole (0.56 mg/kg) with positron emission tomography, using O-15 water and fluorine 18 deoxyglucose (FDG) as perfusion and glucose tracers. MBF at baseline was 0.82 ± 0.13 mL/g/min in normal areas and 0.80 ± 0.15 mL/g/min in areas supplied by stenotic arteries. MBF during dipyridamole was 2.05 ± 0.66 and 1.19 ± 0.66 mL/g/min in normal areas and areas with stenotic arteries, respectively (P ≤ .001). FDG uptake at baseline was 1.36 ± 0.55 in normal areas and 1.57 ± 0.62 in areas supplied by stenotic arteries. FDG uptake after dipyridamole infusion was 1.79 ± 1.1 and 4.04 ± 0.84 in normal areas and areas with stenotic arteries, respectively (P ≤ .001). MBF and FDG uptake were not different between patients with collateral circulation and those without collateral circulation. Conclusions. Increased myocardial glucose uptake was consistently observed after dipyridamole administration in those areas with diminished coronary vasodilatory capacity. The similar MBF and FDG findings in patients with and without collateral circulation may indicate that transmural blood flow redistribution appears to be a possible mechanism of dipyridamole-induced myocardial ischemia. (J Nucl Cardiol 2001;8:339-46.)
To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more ...than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms.
ACC Advocacy: Engage, Influence, Advocate Fry, Edward T A; Jones, Samuel O; Morse, Nick
Journal of the American College of Cardiology,
11/2022, Letnik:
80, Številka:
19
Journal Article
Using data derived from two large New York State registries, this study compared three-year survival rates among patients with multivessel coronary disease who had undergone coronary-artery bypass ...grafting (CABG) and those who had received a coronary stent. Survival rates were uniformly superior with CABG. Although this study was not randomized, it has important implications for the selection of revascularization procedures in patients with multivessel coronary disease.
This study compared three-year survival rates among patients with multivessel coronary disease who had undergone coronary-artery bypass grafting (CABG) and those who had received a coronary stent.
Coronary-artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) have long been the definitive aggressive options for treating patients with coronary artery disease. In the past few years, several randomized clinical trials
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and observational studies
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have examined the relative long-term benefits of these interventions. However, with few exceptions, these studies were conducted before the availability of stenting.
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We used observational data from a very large registry to compare short-term and long-term outcomes among patients with multivessel disease who underwent CABG or stenting in New York State hospitals.
Methods
Databases
The two main databases used in . . .
Two-photon excitation microscopy (TPEM) is used to visualize and track the uptake and movement of anthracene and phenanthrene from a contaminated growth medium into living unmodified roots of maize ...and wheat over a 56-day period. The degradation of anthracene was also directly observed within the cortex cells of both species. The power of this technique is that neither the plant nor the compound require altering (staining or sectioning) to visualize them, meaning they are in their natural form throughout the experiment. Initially both compounds bound to the epidermis along the zone of elongation, passing through the epidermal cells to reach the cortex within the root hair, and branching zones of the root. The PAHs entered the epidermis radially; however, once within the cortex cells this movement was dominated by slow lateral movement of both compounds toward the shoot. Highly focused “streams” of compound were observed to form over time; zones where phenanthrene concentrated extended up to 1500 μm in length over a 56-day period, for example, passing through several adjoining cells, and were detectable in cell walls and cell vacuoles. Radial movement was not observed to extend beyond the cortex cells to reach the vascular tissues of the plant. The longitudinal movement of both compounds was not observed to extend beyond the root base into the stem or vegetative parts of the plant. The lateral movement of both compounds within the cortex cells was dominated by movement within the cell walls, suggesting apoplastic flow through multiple cell walls, but with a low level of symplastic movement to transport compound into the cellular vacuoles. Degradation of anthracene to the partial breakdown products anthrone, anthraquinone, and hydroxyanthraquinone was observed directly in the zones of root elongation and branching. The technique and observations have important applications to the fields of agrochemistry and phytoremediation.
South American (SA) societies are highly vulnerable to droughts and pluvials, but lack of long-term climate observations severely limits our understanding of the global processes driving climatic ...variability in the region. The number and quality of SA climatesensitive tree ring chronologies have significantly increased in recent decades, now providing a robust network of 286 records for characterizing hydroclimate variability since 1400 CE. We combine this network with a self-calibrated Palmer Drought Severity Index (scPDSI) dataset to derive the South American Drought Atlas (SADA) over the continent south of 12°S. The gridded annual reconstruction of austral summer scPDSI is the most spatially complete estimate of SA hydroclimate to date, and well matches past historical dry/wet events. Relating the SADA to the Australia–New Zealand Drought Atlas, sea surface temperatures and atmospheric pressure fields, we determine that the El Niño–Southern Oscillation (ENSO) and the Southern Annular Mode (SAM) are strongly associated with spatially extended droughts and pluvials over the SADA domain during the past several centuries. SADA also exhibits more extended severe droughts and extreme pluvials since the mid-20th century. Extensive droughts are consistent with the observed 20th-century trend toward positive SAM anomalies concomitant with the weakening of midlatitude Westerlies, while low-level moisture transport intensified by global warming has favored extreme rainfall across the subtropics. The SADA thus provides a long-term context for observed hydroclimatic changes and for 21st-century Intergovernmental Panel on Climate Change (IPCC) projections that suggest SA will experience more frequent/ severe droughts and rainfall events as a consequence of increasing greenhouse gas emissions.
The stromal microenvironment of tumors, which is a mixture of hematopoietic and mesenchymal cells, suppresses immune control of tumor growth. A stromal cell type that was first identified in human ...cancers expresses fibroblast activation protein-α (FAP). We created a transgenic mouse in which FAP-expressing cells can be ablated. Depletion of FAP-expressing cells, which made up only 2% of all tumor cells in established Lewis lung carcinomas, caused rapid hypoxic necrosis of both cancer and stromal cells in immunogenic tumors by a process involving interferon-γ and tumor necrosis factor-α. Depleting FAP-expressing cells in a subcutaneous model of pancreatic ductal adenocarcinoma also permitted immunological control of growth. Therefore, FAP-expressing cells are a nonredundant, immune-suppressive component of the tumor microenvironment.
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