Reconstructing property, borders, and sites: nestling the built

The built environment is built for resilience. It is curated to have prominence over natural systems, formulated to withstand, and rebuilt to withstand, once ruined. The power of the biosphere is subverted, however, building to protect against nature undermines opportunities within natural systems to protect us. My thesis is focusing on the problems at play with property and our pressing climate issues. I will be looking at what opportunities exist to deprioritize owned property, to allow for a dispersal of stewardship, and acknowledgment of natural systems

Statins: a role in infected critically ill patients?

Terblanche and colleagues add to the ongoing controversy over the role, if any, for statins in patients with sepsis. The authors note that statins fail to prevent progression to organ dysfunction in critically ill patients. However, like most publications, the study is retrospective and stimulates the controversy but fails to resolve it. The time has come for robust randomized controlled clinical trials

Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute Respiratory Distress Syndrome.

Background:Acute kidney injury (AKI) commonly occurs in patients with sepsis and acute respiratory distress syndrome (ARDS). Objective:To investigate whether statin treatment is protective against AKI in sepsis-associated ARDS. Design:Secondary analysis of data from Statins for Acutely Injured Lungs in Sepsis (SAILS), a randomized controlled trial that tested the impact of rosuvastatin therapy on mortality in patients with sepsis-associated ARDS. Setting:44 hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials Network. Patients:644 of 745 participants in SAILS who had available baseline serum creatinine data and who were not on chronic dialysis. Measurements:Our primary outcome was AKI defined using the Kidney Disease Improving Global Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the primary predictor. Additional covariates include demographics, ARDS etiology, and severity of illness. Methods:We used multivariable logistic regression to analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with stage 1 AKI at randomization. Results:Among individuals without AKI at randomization, rosuvastatin treatment did not change the risk of AKI (adjusted odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum creatinine was adjusted for cumulative fluid balance among those with preexisting stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds ratio: 1.85, 95% CI: 0.70-4.84). Limitations:Sample size, lack of urine output data, and prehospitalization baseline creatinine. Conclusion:Treatment with rosuvastatin in patients with sepsis-associated ARDS did not protect against de novo AKI or worsening of preexisting AKI

Recent advances in understanding and treating acute respiratory distress syndrome [version 1; referees: 2 approved]

Acute respiratory distress syndrome (ARDS) is a clinically and biologically heterogeneous disorder associated with many disease processes that injure the lung, culminating in increased non-hydrostatic extravascular lung water, reduced compliance, and severe hypoxemia. Despite enhanced understanding of molecular mechanisms, advances in ventilatory strategies, and general care of the critically ill patient, mortality remains unacceptably high. The Berlin definition of ARDS has now replaced the American-European Consensus Conference definition. The recently concluded Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG-SAFE) provided worldwide epidemiological data of ARDS including prevalence, geographic variability, mortality, and patterns of mechanical ventilation use. Failure of clinical therapeutic trials prompted the investigation and subsequent discovery of two distinct phenotypes of ARDS (hyper-inflammatory and hypo-inflammatory) that have different biomarker profiles and clinical courses and respond differently to the random application of positive end expiratory pressure (PEEP) and fluid management strategies. Low tidal volume ventilation remains the predominant mainstay of the ventilatory strategy in ARDS. High-frequency oscillatory ventilation, application of recruitment maneuvers, higher PEEP, extracorporeal membrane oxygenation, and alternate modes of mechanical ventilation have failed to show benefit. Similarly, most pharmacological therapies including keratinocyte growth factor, beta-2 agonists, and aspirin did not improve outcomes. Prone positioning and early neuromuscular blockade have demonstrated mortality benefit, and clinical guidelines now recommend their use. Current ongoing trials include the use of mesenchymal stem cells, vitamin C, re-evaluation of neuromuscular blockade, and extracorporeal carbon dioxide removal. In this article, we describe advances in the diagnosis, epidemiology, and treatment of ARDS over the past decade

Evolution of changes in the computed tomography scans of the brain of a patient with left middle cerebral artery infarction: a case report

<p>Abstract</p> <p>Introduction</p> <p>Stroke is a common and important condition in medicine. Effective early management of acute stroke can reduce morbidity and mortality.</p> <p>Case presentation</p> <p>A 63-year-old man presented to the Accident and Emergency department with a history of collapse and progressive right-sided weakness. Clinically this was a cerebrovascular accident affecting the left hemisphere of the brain causing right hemiplegia. Computed tomography scans, performed 3 days apart, showed the evolution of infarction in the brain caused by the thrombus in the left middle cerebral artery. This is one of the early signs for stroke seen on computed tomography imaging and it is called the hyperdense middle cerebral artery sign.</p> <p>Conclusion</p> <p>Patients admitted with a stroke, undergo CT brain within 24 hours. The scan usually takes place at admission into the hospital and is done to rule out a bleed or a space occupying lesion within the brain. A normal CT brain does not confirm a stroke has not taken place. When scanned early, the changes seen on the CT due to an infarction from a thrombus may not have taken place yet. This paper highlights the early changes that can be seen on the CT brain following a stroke caused by infarction due to a thrombus in the middle cerebral artery.</p

Optimal sedative dose of propofol to start MRI in children with cerebral palsy

BACKGROUND: This study was designed to determine the optimal sedative dose of propofol to start brain magnetic resonance imaging (MRI) in children with cerebral palsy (CP). METHODS: Twenty children, aged 0.5-5 years, were administered propofol to achieve a University of Michigan Sedation Scale (UMSS) score ≥ 3 in the MRI room. The proper dose of propofol was determined using the up-and-down method. RESULTS: The ED50 and ED95 for successful sedation with a UMSS ≥ 3 were 2.07 mg/kg (95% CI 1.69-2.56) and 2.69 mg/kg (95% CI 2.35-5.59). Respiratory events occurred in 5 patients and were resolved with neck extension, chin lift, or transient respiratory assistance with successful sedation. CONCLUSIONS: Low dose propofol can safely facilitate the initiation of MRI in children with CPope

Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

OBJECTIVE: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. DESIGN: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). SETTING: Research laboratories of Hannover Medical School and Harvard Medical School. PATIENTS: Septic patients/C57Bl/6 mice and human endothelial cells. INTERVENTIONS: Food and Drug Administration-approved library screening. MEASUREMENTS AND MAIN RESULTS: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. CONCLUSIONS: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage