Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study

Introduction: Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown. Methods: In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N?=?10) or placebo (N?=?10) plus standard of care. ATII was started at a dose of 20?ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65?mmHg. The infusion (either ATII or placebo) was continued for 6?hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65?mmHg. Results: ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6???29.3 mcg/min versus 7.4???12.4 mcg/min for the ATII cohort (P?=?0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P?=?1.00). Conclusion: Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10?ng/kg/min. Trial registration Clinicaltrials.gov NCT01393782. Registered 12 July 2011

Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P \u3c0.002), none of which achieved an AUC \u3e0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169

Clinical evaluation and treatment of phaeochromocytoma

Phaeochromocytoma and extra adrenal paraganglioma are rare neuroendocrine tumours and have the potential to secrete adrenaline, noradrenaline and dopamine causing a myriad of clinical symptoms. Prompt diagnosis is essential for clinicians and requires a multidisciplinary specialist approach for the clinical and laboratory investigation, diagnosis, treatment and follow-up of patients. This paper is an integrated review of the clinical and laboratory evaluation and treatment of patients suspected to have phaeochromocytoma or paraganglioma, highlighting recent developments and best practices from recent published clinical guidelines.</jats:p

Clinical prognostic indicators of dysphagia following prolonged orotracheal intubation in ICU patients

Introduction The development of postextubation wallowing dysfunction is well documented in the literature with high prevalence in most studies. However, there are relatively few studies with specific outcomes that focus on the follow-up of these patients until hospital discharge. The purpose of our study was to determine prognostic indicators of dysphagia in ICU patients submitted to prolonged orotracheal intubation (OTI). Methods We conducted a retrospective, observational cohort study from 2010 to 2012 of all patients over 18 years of age admitted to a university hospital ICU who were submitted to prolonged OTI and subsequently received a bedside swallow evaluation (BSE) by a speech pathologist. The prognostic factors analyzed included dysphagia severity rate at the initial swallowing assessment and at hospital discharge, age, time to initiate oral feeding, amount of individual treatment, number of orotracheal intubations, intubation time and length of hospital stay. Results After we excluded patients with neurologic diseases, tracheostomy, esophageal dysphagia and those who were submitted to surgical procedures involving the head and neck, our study sample size was 148 patients. The logistic regression model was used to examine the relationships between independent variables. In the univariate analyses, we found that statistically significant prognostic indicators of dysphagia included dysphagia severity rate at the initial swallowing assessment, time to initiate oral feeding and amount of individual treatment. In the multivariate analysis, we found that dysphagia severity rate at the initial swallowing assessment remained associated with good treatment outcomes. Conclusions Studies of prognostic indicators in different populations with dysphagia can contribute to the design of more effective procedures when evaluating, treating, and monitoring individuals with this type of disorder. Additionally, this study stresses the importance of the initial assessment ratings

Development and Standardization of a Furosemide Stress Test to Predict the Severity of Acute Kidney Injury

Introduction: In the setting of early acute kidney injury (AKI), no test has been shown to definitively predict the progression to more severe stages. Methods: We investigated the ability of a furosemide stress test (FST) (one-time dose of 1.0 or 1.5 mg/kg depending on prior furosemide-exposure) to predict the development of AKIN Stage-III in 2 cohorts of critically ill subjects with early AKI. Cohort 1 was a retrospective cohort who received a FST in the setting of AKI in critically ill patients as part of Southern AKI Network. Cohort 2 was a prospective multicenter group of critically ill patients who received their FST in the setting of early AKI. Results: We studied 77 subjects; 23 from cohort 1 and 54 from cohort 2; 25 (32.4%) met the primary endpoint of progression to AKIN-III. Subjects with progressive AKI had significantly lower urine output following FST in each of the first 6 hours (p\u3c0.001). The area under the receiver operator characteristic curves for the total urine output over the first 2 hours following FST to predict progression to AKIN-III was 0.87 (p = 0.001). The ideal-cutoff for predicting AKI progression during the first 2 hours following FST was a urine volume of less than 200mls(100ml/hr) with a sensitivity of 87.1% and specificity 84.1%.Conclusions: The FST in subjects with early AKI serves as a novel assessment of tubular function with robust predictive capacity to identify those patients with severe and progressive AKI. Future studies to validate these findings are warranted. © 2013 Chawla et al. licensee BioMed Central Ltd

Household Food Security Data Consensus Statement

Food insecurity in Australia is increasing, but a lack of consistent, regular monitoring and reporting of food insecurity using comprehensive, validated tools is limiting timely intervention. Regular monitoring is urgently needed from state/ territory and federal governments. Reporting of the prevalence of household food security needs to reflect levels of severity (marginal, moderate and severe food insecurity) in each state and territory across Australia. Commonly used short tools comprising one or two questions are inadequate for assessing the true prevalence of food insecurity and result in serious underestimation. The United States Department of Agriculture (USDA) 18-item Household Food Security Survey Module (HFSSM) should be adopted across settings to provide the most valid, internationally comparable data on food insecurity for both adults and children

Brain network adaptability across task states.

Activity in the human brain moves between diverse functional states to meet the demands of our dynamic environment, but fundamental principles guiding these transitions remain poorly understood. Here, we capitalize on recent advances in network science to analyze patterns of functional interactions between brain regions. We use dynamic network representations to probe the landscape of brain reconfigurations that accompany task performance both within and between four cognitive states: a task-free resting state, an attention-demanding state, and two memory-demanding states. Using the formalism of hypergraphs, we identify the presence of groups of functional interactions that fluctuate coherently in strength over time both within (task-specific) and across (task-general) brain states. In contrast to prior emphases on the complexity of many dyadic (region-to-region) relationships, these results demonstrate that brain adaptability can be described by common processes that drive the dynamic integration of cognitive systems. Moreover, our results establish the hypergraph as an effective measure for understanding functional brain dynamics, which may also prove useful in examining cross-task, cross-age, and cross-cohort functional change

Intravenous angiotensin II for the treatment of high-output shock (ATHOS trial): a pilot study

INTRODUCTION: Patients with distributive shock who require high dose vasopressors have a high mortality. Angiotensin II (ATII) may prove useful in patients who remain hypotensive despite catecholamine and vasopressin therapy. The appropriate dose of parenteral angiotensin II for shock is unknown. METHODS: In total, 20 patients with distributive shock and a cardiovascular Sequential Organ Failure Assessment score of 4 were randomized to either ATII infusion (N =10) or placebo (N =10) plus standard of care. ATII was started at a dose of 20 ng/kg/min, and titrated for a goal of maintaining a mean arterial pressure (MAP) of 65 mmHg. The infusion (either ATII or placebo) was continued for 6 hours then titrated off. The primary endpoint was the effect of ATII on the standing dose of norepinephrine required to maintain a MAP of 65 mmHg. RESULTS: ATII resulted in marked reduction in norepinephrine dosing in all patients. The mean hour 1 norepinephrine dose for the placebo cohort was 27.6 ± 29.3 mcg/min versus 7.4 ± 12.4 mcg/min for the ATII cohort (P =0.06). The most common adverse event attributable to ATII was hypertension, which occurred in 20% of patients receiving ATII. 30-day mortality for the ATII cohort and the placebo cohort was similar (50% versus 60%, P =1.00). CONCLUSION: Angiotensin II is an effective rescue vasopressor agent in patients with distributive shock requiring multiple vasopressors. The initial dose range of ATII that appears to be appropriate for patients with distributive shock is 2 to 10 ng/kg/min. TRIAL REGISTRATION: Clinicaltrials.gov NCT01393782. Registered 12 July 2011