Abstract Since their widespread introduction more than half a century ago, Intensive Care Units (ICUs) have become an integral part of the health care system. While most ICUs are found in high income ...countries, they are increasingly a feature of health care systems in low and middle income countries. The World Federation of Societies of Intensive and Critical Care Medicine (WFSICCM) convened a task force whose objective was to answer the question, “What is an ICU” in an internationally meaningful manner, and to develop a system for stratifying ICUs on the basis of the intensity of the care they provide. We undertook a scoping review of the peer-reviewed and grey literature to assemble existing models for ICU stratification. Based on these, and on discussions amongst task force members by teleconference and two face-to-face meetings, we present a proposed definition and classification of ICUs. An ICU is an organized system for the provision of care to critically ill patients that provides intensive and specialized medical and nursing care, an enhanced capacity for monitoring, and multiple modalities of physiologic organ support to sustain life during a period of life-threatening organ system insufficiency. While an ICU is based in a defined geographic area of a hospital, its activities often extend beyond the walls of the physical space to include the emergency department, hospital ward, and follow-up clinic. A Level One ICU is capable of providing oxygen, non-invasive monitoring, and more intensive nursing care than on a ward, while a Level Two ICU can provide invasive monitoring and basic life support for a short period of time. A Level Three ICU provides a full spectrum of monitoring and life support technologies, serves as a regional resource for the care of critically ill patients, and may play an active role in developing the specialty of intensive care through research and education. A formal definition and descriptive framework for ICUs can inform health care decision-makers in planning and measuring capacity, and provide clinicians and patients with a benchmark to evaluate the level of resources available for clinical care.
There is increasing recognition that platelets have a functional role in the pathophysiology of sepsis, though this role has not been precisely defined. Whether sepsis alters the human platelet ...transcriptome and translational landscape has never been established. We used parallel techniques of RNA sequencing and ribosome footprint profiling to interrogate the platelet transcriptome and translatome in septic patients and healthy donors. We identified 1806 significantly differentially expressed (false discovery rate <0.05) transcripts in platelets from septic patients. Platelet translational events during sepsis were also upregulated. To explore the relevance of a murine model of sepsis, cecal ligation and puncture (CLP), we compared sepsis-induced changes in platelet gene expression between septic patients and mice subjected to CLP. Platelet transcriptional (ρ = 0.42, P = 3.2 × 10−285) and translational (ρ = 0.65, P = 1.09 × 10−56) changes were significantly correlated between septic patients and mice. We focused on ITGA2B, tracking and validating the expression, regulation, and functional impact of changes in ITGA2B during sepsis. Increased ITGA2B was identified in bone marrow megakaryocytes within 24 hours of sepsis onset. Subsequent increases in ITGA2B were seen in circulating platelets, suggesting dynamic trafficking of the messenger RNA. Transcriptional changes in ITGA2B were accompanied by de novo protein synthesis of αIIb and integrin αIIbβ3 activation. Increased αIIb was associated with mortality in humans and mice. These findings provide previously unrecognized evidence that human and murine sepsis similarly alters the platelet transcriptional and translational landscape. Moreover, ITGA2B is upregulated and functional in sepsis due to trafficking from megakaryocytes and de novo synthesis in platelets and is associated with increased mortality.
•Sepsis triggers transcriptional and translational alterations in platelets.•Sepsis-induced upregulation of ITGA2B predicts mortality.
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Evolving evidence indicates that platelets and megakaryocytes (MKs) have unexpected activities in inflammation and infection; whether viral infections upregulate biologically active, antiviral immune ...genes in platelets and MKs is unknown, however. We examined antiviral immune genes in these cells in dengue and influenza infections, viruses that are global public health threats. Using complementary biochemical, pharmacological, and genetic approaches, we examined the regulation and function of interferon-induced transmembrane protein 3 (IFITM3), an antiviral immune effector gene not previously studied in human platelets and MKs. IFITM3 was markedly upregulated in platelets isolated from patients during clinical influenza and dengue virus (DENV) infections. Lower IFITM3 expression in platelets correlated with increased illness severity and mortality in patients. Administering a live, attenuated DENV vaccine to healthy subjects significantly increased platelet IFITM3 expression. Infecting human MKs with DENV selectively increased type I interferons and IFITM3. Overexpression of IFITM3 in MKs was sufficient to prevent DENV infection. In naturally occurring, genetic loss-of-function studies, MKs from healthy subjects harboring a homozygous mutation in IFITM3 (rs12252-C, a common single-nucleotide polymorphism in areas of the world where DENV is endemic) were significantly more susceptible to DENV infection. DENV-induced MK secretion of interferons prevented infection of bystander MKs and hematopoietic stem cells. Thus, viral infections upregulate IFITM3 in human platelets and MKs, and IFITM3 expression is associated with adverse clinical outcomes. These observations establish, for the first time, that human MKs possess antiviral functions, preventing DENV infection of MKs and hematopoietic stem cells after local immune signaling.
•Viral infections upregulate IFITM3 in human platelets and MKs, triggering rapid antiviral immune responses.•MKs are effective immune cells that prevent virus infection in naive MKs but also limit infection in bystander hematopoietic stem cells.
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Brain maturation is delayed in infants with complex congenital heart defects Licht, Daniel J., MD; Shera, David M., ScD; Clancy, Robert R., MD ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
03/2009, Letnik:
137, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Objective Small head circumferences and white matter injury in the form of periventricular leukomalacia have been observed in populations of infants with severe forms of congenital heart defects. ...This study tests the hypothesis that congenital heart defects delay in utero structural brain development. Methods Full-term infants with hypoplastic left heart syndrome or transposition of the great arteries were prospectively evaluated with preoperative brain magnetic resonance imaging. Patients with independent risk factors for abnormal brain development (shock, end-organ injury, or intrauterine growth retardation) were excluded. Outcome measures included head circumferences and the total maturation score on magnetic resonance imaging. Total maturation score is a previously validated semiquantitative anatomic scoring system used to assess whole brain maturity. The total maturation score evaluates 4 parameters of maturity: (1) myelination, (2) cortical infolding, (3) involution of glial cell migration bands, and (4) presence of germinal matrix tissue. Results The study cohort included 29 neonates with hypoplastic left heart syndrome and 13 neonates with transposition of the great arteries at a mean gestational age of 38.9 ± 1.1 weeks. Mean head circumference was 1 standard deviation below normal. The mean total maturation score for the cohort was 10.15 ± 0.94, significantly lower than reported normative data in infants without congenital heart defects, corresponding to a delay of 1 month in structural brain development. Conclusion Before surgery, term infants with hypoplastic left heart syndrome and transposition of the great arteries have brains that are smaller and structurally less mature than expected. This delay in brain development may foster susceptibility to periventricular leukomalacia in the preoperative, intraoperative, and postoperative periods.
In this comparison of CT colonography and optical colonoscopy in 2600 asymptomatic study participants 50 years of age or older at 15 centers, 90% of large colorectal adenomas and adenocarcinomas ...detected by optical colonoscopy were also detected on CT colonography, and 10% were missed by CT colonography.
In this comparison of CT colonography and optical colonoscopy, 90% of large colorectal adenomas and adenocarcinomas detected by optical colonoscopy were also detected on CT colonography.
Colorectal cancer is the third most common cancer and the second leading cause of death from cancer in the United States, with an estimated 154,000 new cases and 52,000 deaths in 2007.
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There is an enormous opportunity to save lives with broadly applied, widely accepted early-detection programs, since the natural history of colorectal cancer permits the recognition and curative treatment of both precursor adenomas and localized cancers. According to data from multiple sources, mortality from colorectal cancer is reduced with regular screening.
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Despite its effectiveness, colorectal-cancer screening remains underused for many reasons, including drawbacks in terms of the performance, . . .
The IDEAL IMPLANT ® Structured Breast Implant utilizes different technology than unstructured saline or silicone gel implants, making it a third type of implant. FDA and Health Canada granted ...approval in November 2014. This saline-filled implant has an internal structure consisting of a series of nested shells that support the upper pole when upright and control movement of the saline to provide a natural feel. Because women can look in the mirror to know their implants are intact, they have peace of mind. In contrast, most women are concerned about silicone gel implant ruptures, which are silent and require FDA-recommended MRI or ultrasound scans for detection.
This US trial enrolled 502 women: 399 for primary and 103 for revision augmentation. Investigators were 45 ABPS certified plastic surgeons at 35 sites. Of the 502 women enrolled, 426 (84.9%) completed 10-year follow-up visits, a higher percentage than all other FDA breast implant trials.
Through 10 years of follow-up, surgeon satisfaction was 94.8% for primary and 87.4% for revision augmentation; patient satisfaction was 92.7% for primary and 82.3% for revision augmentation. Cumulative Kaplan-Meier risk rates for two major adverse events were lower than in the silicone gel implant trials: Baker Class III & IV capsular contracture was 6.6% for primary, 11.5% for revision augmentation; rupture/deflation was 3.7% for primary, 4.7% for revision augmentation.
10-year results from 426 women show the IDEAL IMPLANT has high patient and surgeon satisfaction, a low rate of capsular contracture and a low rate of rupture/deflation.
Neutrophil granulocytes, also called polymorphonuclear leukocytes (PMNs), extrude molecular lattices of decondensed chromatin studded with histones, granule enzymes, and antimicrobial peptides that ...are referred to as neutrophil extracellular traps (NETs). NETs capture and contain bacteria, viruses, and other pathogens. Nevertheless, experimental evidence indicates that NETs also cause inflammatory vascular and tissue damage, suggesting that identifying pathways that inhibit NET formation may have therapeutic implications. Here, we determined that neonatal NET-inhibitory factor (nNIF) is an inhibitor of NET formation in umbilical cord blood. In human neonatal and adult neutrophils, nNIF inhibits key terminal events in NET formation, including peptidyl arginine deiminase 4 (PAD4) activity, neutrophil nuclear histone citrullination, and nuclear decondensation. We also identified additional nNIF-related peptides (NRPs) that inhibit NET formation. nNIFs and NRPs blocked NET formation induced by pathogens, microbial toxins, and pharmacologic agonists in vitro and in mouse models of infection and systemic inflammation, and they improved mortality in murine models of systemic inflammation, which are associated with NET-induced collateral tissue injury. The identification of NRPs as neutrophil modulators that selectively interrupt NET generation at critical steps suggests their potential as therapeutic agents. Furthermore, our results indicate that nNIF may be an important regulator of NET formation in fetal and neonatal inflammation.
Platelets are chief effector cells in hemostasis. In addition, however, their specializations include activities and intercellular interactions that make them key effectors in inflammation and in the ...continuum of innate and adaptive immunity. This review focuses on the immune features of human platelets and platelets from experimental animals and on interactions between inflammatory, immune, and hemostatic activities of these anucleate but complex and versatile cells. The experimental findings and evidence for physiologic immune functions include previously unrecognized biologic characteristics of platelets and are paralleled by new evidence for unique roles of platelets in inflammatory, immune, and thrombotic diseases.
Advective–diffusive transport of passive scalars in confined environments (e.g. vessels and channels) within a network is of fundamental importance in a plethora of biological and geophysical ...phenomena. We conduct a leading-order analysis, consistent with the theory of hydrodynamic dispersion, which averages out the radial variability within a vessel. One-dimensional solutions for individual vessels (edges of a network), obtained for arbitrary (undefined) transient Dirichlet boundary conditions, serve as a building block for a network model. A network transport solution is developed by iteratively linking single-vessel solutions to each other in a bifurcating fractal tree model, i.e. at nodes of the network. We find transport behaviour to be strongly affected by the network geometry and daughter vessels to significantly impact the rate of transport in the upstream parent vessels.
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