Proceedings of the ISCT scientific signature series symposium, "Advances in cell and gene therapies for lung diseases and critical illnesses": International Society for Cell & Gene Therapy, Burlington VT, US, July 16, 2021.

The ISCT Scientific Signature Series Symposium "Advances in Cell and Gene Therapies for Lung Diseases and Critical Illnesses" was held as an independent symposium in conjunction with the biennial meeting, "Stem Cells, Cell Therapies, and Bioengineering in Lung Biology and Diseases," which took place July 12-15, 2021, at the University of Vermont. This is the third Respiratory System-based Signature Series event; the first 2, "Tracheal Bioengineering, the Next Steps" and "Cellular Therapies for Pulmonary Diseases and Critical Illnesses: State of the Art of European Science," took place in 2014 and 2015, respectively. Cell- and gene-based therapies for respiratory diseases and critical illnesses continue to be a source of great promise and opportunity. This reflects ongoing advancements in understanding of the mechanisms by which cell-based therapies, particularly those using mesenchymal stromal cells (MSCs), can mitigate different lung injuries and the increasing sophistication with which preclinical data is translated into clinical investigations. This also reflects continuing evolution in gene transfer vectors, including those designed for in situ gene editing in parallel with those targeting gene or cell replacement. Therefore, this symposium convened global thought leaders in a forum designed to catalyze communication and collaboration to bring the greatest possible innovation and value of cell- and gene-based therapies for patients with respiratory diseases and critical illnesses.

Blood conservation strategies to reduce the need for red blood cell transfusion in critically ill patients.

Anemia commonly affects critically ill patients. The causes are multifactorial and include acute blood loss, blood loss from diagnostic testing and blunted red blood cell production. Blood transfusions are frequently given to patients in intensive care units to treat low hemoglobin levels due to either acute blood loss or subacute anemia associated with critical illness. Although blood transfusion is a life-saving therapy, evidence suggests that it may be associated with an increased risk of morbidity and mortality. A number of blood conservation strategies exist that may mitigate anemia in hospital patients and limit the need for transfusion. These strategies include the use of hemostatic agents, hemoglobin substitutes and blood salvage techniques, the reduction of blood loss associated with diagnostic testing, the use of erythropoietin and the use of restrictive blood transfusion triggers. Strategies to reduce blood loss associated with diagnostic testing and the use of hemostatic agents and erythropoietin result in higher hemoglobin levels, but they have not been shown to reduce the need for blood transfusions or to improve clinical outcomes. Lowering the hemoglobin threshold at which blood is transfused will reduce the need for transfusions and is not associated with increased morbidity or mortality among most critically ill patients without active cardiac disease. Further research is needed to determine the potential roles for other blood conservation strategies.

Prediction scores do not correlate with clinically adjudicated categories of pulmonary embolism in critically ill patients.

BACKGROUND: Prediction scores for pretest probability of pulmonary embolism (PE) validated in outpatient settings are occasionally used in the intensive care unit (ICU). OBJECTIVE: To evaluate the correlation of Geneva and Wells scores with adjudicated categories of PE in ICU patients. METHODS: In a randomized trial of thromboprophylaxis, patients with suspected PE were adjudicated as possible, probable or definite PE. Data were then retrospectively abstracted for the Geneva Diagnostic PE score, Wells, Modified Wells and Simplified Wells Diagnostic scores. The chance-corrected agreement between adjudicated categories and each score was calculated. ANOVA was used to compare values across the three adjudicated PE categories. RESULTS: Among 70 patients with suspected PE, agreement was poor between adjudicated categories and Geneva pretest probabilities (kappa=0.01 [95% CI -0.0643 to 0.0941]) or Wells pretest probabilities (kappa=-0.03 [95% CI -0.1462 to 0.0914]). Among four possible, 16 probable and 50 definite PEs, there were no significant differences in Geneva scores (possible = 4.0, probable = 4.7, definite = 4.5; P=0.90), Wells scores (possible = 2.8, probable = 4.9, definite = 4.1; P=0.37), Modified Wells (possible = 2.0, probable = 3.4, definite = 2.9; P=0.34) or Simplified Wells (possible = 1.8, probable = 2.8, definite = 2.4; P=0.30). CONCLUSIONS: Pretest probability scores developed outside the ICU do not correlate with adjudicated PE categories in critically ill patients. Research is needed to develop prediction scores for this population.