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Background High dose vasopressors portend poor outcome in vasodilatory shock. We aimed to evaluate the impact of baseline vasopressor dose on outcomes in patients treated with angiotensin II (AT II). Methods Exploratory post-hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS-3) trial data. The ATHOS-3 trial randomized 321 patients with vasodilatory shock, who remained hypotensive (mean arterial pressure of 55–70 mmHg) despite receiving standard of care vasopressor support at a norepinephrine-equivalent dose (NED) > 0.2 µg/kg/min, to receive AT II or placebo, both in addition to standard of care vasopressors. Patients were grouped into low (≤ 0.25 µg/kg/min; n = 104) or high (> 0.25 µg/kg/min; n = 217) NED at the time of study drug initiation. The primary outcome was the difference in 28-day survival between the AT II and placebo subgroups in those with a baseline NED ≤ 0.25 µg/kg/min at the time of study drug initiation. Results Of 321 patients, the median baseline NED in the low-NED subgroup was similar in the AT II (n = 56) and placebo (n = 48) groups (median of each arm 0.21 µg/kg/min, p  = 0.45). In the high-NED subgroup, the median baseline NEDs were also similar (0.47 µg/kg/min AT II group, n = 107 vs. 0.45 µg/kg/min placebo group, n = 110, p  = 0.75). After adjusting for severity of illness, those randomized to AT II in the low-NED subgroup were half as likely to die at 28-days compared to placebo (HR 0.509; 95% CI 0.274–0.945, p  = 0.03). No differences in 28-day survival between AT II and placebo groups were found in the high-NED subgroup (HR 0.933; 95% CI 0.644–1.350, p  = 0.71). Serious adverse events were less frequent in the low-NED AT II subgroup compared to the placebo low-NED subgroup, though differences were not statistically significant, and were comparable in the high-NED subgroups. Conclusions This exploratory post-hoc analysis of phase 3 clinical trial data suggests a potential benefit of AT II introduction at lower doses of other vasopressor agents. These data may inform design of a prospective trial. Trial registration : The ATHOS-3 trial was registered in the clinicaltrials.gov repository (no. NCT02338843). Registered 14 January 2015.

Changes in receptor signaling, excessive production of nitric oxide, and absolute or relative deficiencies of vasoactive hormones, including cortisol, vasopressin, and angiotensin II, play a role. Interest was re-ignited following the Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3) study, a randomized controlled trial in patients with refractory shock which confirmed that Ang II was effective at maintaining mean arterial pressure and reducing norepinephrine requirements without an increase in side effects [1]. Pulmonary capillary endothelium-bound angiotensin-converting enzyme activity in acute lung injury.

During continuous renal replacement therapy (CRRT), anticoagulants are recommended for patients at low risk of bleeding and not already receiving systemic anticoagulants. Current anticoagulants used in CRRT in the US are systemic heparins or regional citrate. To better understand use of anticoagulants for CRRT in the US, we surveyed nephrologists and critical care medicine (CCM) specialists. The survey contained 30 questions. Respondents were board certified and worked in intensive care units of academic medical centers or community hospitals. 150 physicians (70 nephrologists and 80 CCM) completed the survey. Mean number of CRRT machines in use increased ∼30% from the pre-pandemic era to 2022. Unfractionated heparin was the most used anticoagulant (43% of estimated patients) followed by citrate (28%). Respondents reported 29% of patients received no anticoagulant. Risk of hypocalcemia (52%) and citrate safety (42%) were the predominant reasons given for using no anticoagulant instead of citrate in heparin-intolerant patients. 84% said filter clogging was a problem when no anticoagulant was used, and almost 25% said increased transfusions were necessary. Respondents using heparin (  = 131) considered it inexpensive and easily obtainable, although of moderate safety, citing concerns of heparin-induced thrombocytopenia and bleeding. Anticoagulant citrate dextrose solution was the most used citrate. Respondents estimated that 37% of patients receiving citrate develop hypocalcemia and 17% citrate lock. Given the increased use of CRRT and the lack of approved, safe, and effective anticoagulant choices for CRRT in the US, effective use of current and other anticoagulant options needs to be evaluated.

At the participating centers, all patients with reverse transcriptase polymerase chain reaction (rtPCR) positive testing for SARS-CoV-2, who received V-V ECMO from March 12 to June 5, 2020 (i.e., during the first wave of the pandemic), were included. [...]even though 90-day-survival of patients aged ≥ 71 years was significantly lower than for patients < 71 years, not all treatments in this elderly population ended fatal. [...]age limits should be viewed with caution and decisions for or against the use of ECMO for patients above 70 years of age should be performed on an individual case-by-case level. [...]our data may support the use of V-V ECMO in severe COVID-19 ARDS, also after prolonged periods of mechanical ventilation in selected patients. Collaborating authors (COVEC-study group): Jeff DellaVolpe, Methodist Hospital, San Antonio, Texas, USA; Dominik Scharpf, SLK-Hospital Heilbronn, Germany; Matthias Ulmer, RKH Hospital Ludwigsburg, Germany; Maximilian Halbe, Heart Center, University Hospital Zurich, Switzerland; Alexander Vogt, Department of Medicine III, University Clinic Halle (Saale), Germany; Raj Ramanan, University of Pittsburgh Medical Center (UPMC), Pennsylvania, USA; David Boldt, UCLA Healthcare System, Los Angeles, USA; Stephanie-Susanne Stecher, Medical Department II, LMU Hospital Munich, Germany; Andrea Montisci, Istituto Clinico Sant’Ambrogio, University of Milan, Italy; Tobias Spangenberg, Department of Cardiology, Angiology and Intensive Care, Marien Hospital Hamburg, Germany; Olivier Marggraf, Asklepios Clinic North, Hamburg, Germany; Chandra Kunavarapu, Methodist Hospital, San Antonio, Texas, USA; Lorenzo Peluso, Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium; Sebastian Muenz, SLK-Hospital Heilbronn, Germany; Monica Buerle, RKH Hospital Ludwigsburg, Germany; Naveen G. Nagaraj, Heart Center, University Hospital Zurich, Switzerland; Sebastian Nuding, Department of Medicine III, University Clinic Halle (Saale), Germany; Catalin Toma, University of Pittsburgh Medical Center (UPMC), Pennsylvania, USA; Vadim Gudzenko, UCLA Healthcare System, Los Angeles, USA; Hans Joachim Stemmler, Medical Department III, LMU Hospital Munich, Germany; Federico Pappalardo, Department of Anesthesia and Intensive Care, IRCCS ISMETT, UPMC Italy, Palermo, Italy; Georg Trummer, Department of Cardiovascular Surgery, Heart Center, University of Freiburg, Germany; Christoph Benk, Department of Cardiovascular Surgery, Heart Center, University of Freiburg, Germany; Guido Michels, Department of Acute and Emergency Care, St. Antonius Hospital Eschweiler, Eschweiler, Germany; Christoph Bode, Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany, Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany; Daniel Duerschmied, Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany, Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany; Constantin von zur Muehlen, Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany, Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany; Klaus Kaier, Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany, Institute of Medical Biometry and Statistics, Faculty of Medicine, University of Freiburg, Germany, Daniel Brodie, Columbia University College of Physicians & Surgeons/New York-Presbyterian Hospital, New York, USA, Center for Acute Respiratory Failure, Columbia University Medical Center, New York, USA; Tobias Wengenmayer, Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Germany, Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Germany.

The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival. Methods: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V-V ECMO (PRESERVE) Score, and 30-day survival. Results: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic—AUROC) ranged between 0.548 and 0.605. Conclusions: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V-V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.

As universities experience a declining number of applicants for their MBA programs, business schools are pressured to adjust their curriculum. This paper suggests using conjoint analysis to understand the needs of prospective students. The authors segmented the market preferences toward the university’s MBA program into three groups – high, medium and low utility. The high utility group preferred the current program, the low group would likely never consider it, but the medium group could be enticed with programmatic changes. The findings suggest that an increase in applications could occur by addressing the needs of the medium group.

In this article, the authors provide a historical review of how the U.S. government has funded its participation in major wars during the past 150 years. They focus attention on five conflicts--the Civil War, World War I, World War II, the Korean War and the Vietnam War. Those conflicts were funded in different ways, with each funding method having consequences for the economy. Those wars were selected because the spending associated with each conflict accounted for a significant share of the economy, in each case more than 7 percent of GDP (Edelstein 2000). They present useful lesson ideas for incorporating a discussion of war finance into a history course or a stand-alone economics course and give details in the appendix. Ways of using a variety of resources that are available from the Internet are also suggested.

Provides an introduction to the Internet with special focus on access issues, electronic communication, and tools for making the Internet easier to use. Identifies selected Internet resources appropriate for social studies. Includes three lesson plan ideas and five tables listing Internet resources. (CFR)

War offer very interesting case studies for learning about such economic concepts as opportunity cost, deficit spending, taxation, and hyperinflation. Here, Boldt and Kassis provide insights and lesson ideas for social studies teachers who might be interested in integrating economic concepts within the context of teaching about military conflicts. They focus attention on five conflicts-the Civil War, WWII, the Korean War and the Vietnam War.

When human lymphocytes are cultured in the presence of phytomitogens, 70-90% of the cells undergo blast transformation and synthesize DNA. However, less than 40% of these lymphocytes actually undergo mitosis while 35-90% of the newly synthesized DNA is excreted into the media. The release of DNA by the cells is selective since experiments with [14C]uridine indicate that RNA is not lost into the culture media. DNA excretion occurs under many culture conditions. The excreted DNA has an estimated molecular weight of 3 to 12 × 106as determined by gel filtration on Sepharose 2B. It forms a single sharp peak at a density of 1.055 g/cm3when examined by sucrose density gradient centrifugation, suggesting that the DNA is complexed to protein or lipid.