Purpose: To apply cross-correlation delay (XCD) analysis to myocardial phase contrast magnetic resonance (PCMR) tissue velocity data and to compare XCD to three established "time-to-peak" dyssynchrony parameters. Materials and Methods: Myocardial tissue velocity was acquired using PCMR in 10 healthy volunteers (negative controls) and 10 heart failure patients who met criteria for cardiac resynchronization therapy (positive controls). All dyssynchrony parameters were computed from PCMR velocity curves. Sensitivity, specificity, and receiver operator curve (ROC) analysis for separating positive and negative controls were computed for each dyssynchrony parameter. Results: XCD had higher sensitivity (90%) and specificity (100%) for discriminating between normal and patient groups than any of the time-to-peak dyssynchrony parameters. ROC analysis showed that XCD was the best parameter for separating the positive and negative control groups. Conclusion:XCD is superior to time-to-peak dyssynchrony parameters for discriminating between subjects with and without dyssynchrony and may aid in the selection of patients for cardiac resynchronization therapy.

Objective: This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease. Data Sources: Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital). Study Selection: Not applicable. Data Extraction: Not applicable. Data Synthesis: Not applicable. Conclusion: In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment.

Objective: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock," published in 2004. Design: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods: We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results: Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/ vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

The high incidence of cardiovascular events in chronic kidney disease (CKD) warrants an accurate evaluation of risk aimed at reducing the burden of disease and its consequences. The use of biomarkers to identify patients at high risk has been in use in the general population for several decades and has received mixed reactions in the medical community. Some practitioners have become staunch supporters and users while others doubt the utility of biomarkers and rarely measure them. In CKD patients numerous markers similar to those used in the general population and others more specific to the uremic population have emerged; however their utility for routine clinical application remains to be fully elucidated. The reproducibility and standardization of the serum assays are serious limitations to the broad implementation of these tests. The lack of focused research and validation in randomized trials rather than ad hoc measurement of multiple serum markers in observational studies is also cause for concern related to the clinical applicability of these markers. We review the current literature on biomarkers that may have a relevant role in field of nephrology.

As a result of the improved survival of patients with heart failure (HF) and the overall rise in the prevalence of HF,1 the number of patients in advanced (stage D) HF continues to increase, thus exceeding the limited availability of donor organs by a wide margin.2 Initially used primarily as a bridge to heart transplantation, mechanical circulatory support is now increasingly offered as a destination therapy to patients with advanced HF in clinical deterioration who are not candidates for transplantation. Improvement in survival to 80% at 1-year postimplantation3 has steadily followed the development of new technologies such as the continuous-flow pump, which now encompasses 99% of left ventricular assist devices (LVADs),3 and improvements in patient and device management. Far from being a panacea, mechanical circulatory support is still fraught with challenges. Among them, post-LVAD right ventricular failure (RVF) is a major cause of morbidity and mortality.

We sought to examine trends in the race-specific incidence of acute respiratory failure in the United States. Design: Retrospective cohort study. Setting: We used the National Hospital Discharge Survey database (1992-2007), an annual survey of approximately 500 hospitals weighted to provide national hospitalization estimates. Patients: All incident cases of noncardiogenic acute respiratory failure hospitalized in the United States. INTERVENTIONS:: None. Measurements and Main Results: We identified noncardiogenic acute respiratory failure by the presence of International Classification of Diseases, Ninth Revision, codes for respiratory failure or pulmonary edema (518.4, 518.5, 518.81, and 518.82) and mechanical ventilation (96.7×), excluding congestive heart failure. Incidence rates were calculated using yearly census estimates standardized to the age and sex distribution of the 2000 census population. Annual cases of noncardiogenic acute respiratory failure increased from 86,755 in 1992 to 323,474 in 2007. Noncardiogenic acute respiratory failure among black Americans increased from 56.4 (95% confidence interval 39.7-73.1) to 143.8 (95% confidence interval 123.8-163.8) cases per 100,000 in 1992 and 2007, respectively. Among white Americans, the incidence of noncardiogenic acute respiratory failure increased from 31.2 (95% confidence interval 26.2-36.5) to 94.0 (95% confidence interval 86.7-101.2) cases per 100,000 in 1992 and 2007, respectively. The average annual incidence of noncardiogenic acute respiratory failure over the entire study period was 95.1 (95% confidence interval 93.9-96.4) cases per 100,000 for black Americans compared to 66.5 (95% confidence interval 65.8-67.2) cases per 100,000 for white Americans (rate ratio 1.43, 95% confidence interval 1.42-1.44). Overall in-hospital mortality was greater for other-race Americans, but only among patients with two or more organ failures (57% [95% confidence interval 56%-59%] for other race, 51% [95% confidence interval 50%-52%] for white, 50% [95% confidence interval 49%-51%] for black). Conclusions: The incidence of noncardiogenic acute respiratory failure in the United States increased between 1992 and 2007. Black and other-race Americans are at greater risk of developing noncardiogenic acute respiratory failure compared to white Americans.

Objective: Angiotensin II is an endogenous hormone with vasopressor and endocrine activities. This is a systematic review of the safety of IV angiotensin II. Data Sources: PubMed, Medline, Scopus, and Cochrane. Study Selection: Studies in which human subjects received IV angiotensin II were selected whether or not safety was discussed. Data Extraction: In total, 18,468 studies were screened by two reviewers and one arbiter. One thousand one hundred twenty-four studies, in which 31,281 participants received angiotensin II (0.5-3,780 ng/kg/min), were selected. Data recorded included number of subjects, comorbidities, angiotensin II dose and duration, pressor effects, other physiologic and side effects, and adverse events. Data Synthesis: The most common nonpressor effects included changes in plasma aldosterone, renal function, cardiac variables, and electrolytes. Adverse events were infrequent and included headache, chest pressure, and orthostatic symptoms. The most serious side effects were exacerbation of left ventricular failure in patients with congestive heart failure and bronchoconstriction. One patient with congestive heart failure died from refractory left ventricular failure. Refractory hypotensive shock was fatal in 55 of 115 patients treated with angiotensin II in case studies, cohort studies, and one placebo-controlled study. One healthy subject died after a pressor dose of angiotensin II was infused continuously for 6 days. No other serious adverse events attributable to angiotensin II were reported. Heterogeneity in study design prevented meta-analysis. Conclusion: Adverse events associated with angiotensin II were infrequent; however, exacerbation of asthma and congestive heart failure and one fatal cerebral hemorrhage were reported. This systematic review supports the notion that angiotensin II has an acceptable safety profile for use in humans.