Contemporary Use of Venoarterial Extracorporeal Membrane Oxygenation: Insights from the Multicenter RESCUE Registry

BackgroundVenoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a life-saving therapy for patients with cardiovascular collapse, but identifying patients unlikely to benefit remains a challenge.Methods and ResultsWe created the RESCUE registry, a retrospective, observational registry of adult patients treated with VA-ECMO between January 2007 and June 2017 at 3 high-volume centers (Columbia University, Duke University, and Washington University) to describe short-term patient outcomes. In 723 patients treated with VA-ECMO, the most common indications for deployment were postcardiotomy shock (31%), cardiomyopathy (including acute heart failure) (26%), and myocardial infarction (17%). Patients frequently suffered in-hospital complications, including acute renal dysfunction (45%), major bleeding (41%), and infection (33%). Only 40% of patients (n = 290) survived to discharge, with a minority receiving durable cardiac support (left ventricular assist device [n = 48] or heart transplantation [n = 7]). Multivariable regression analysis identified risk factors for mortality on ECMO as older age (odds ratio [OR], 1.26; 95% confidence interval [CI], 1.12–1.42) and female sex (OR, 1.44; 95% CI, 1.02–2.02) and risk factors for mortality after decannulation as higher body mass index (OR 1.17; 95% CI, 1.01-1.35) and major bleeding while on ECMO support (OR, 1.92; 95% CI, 1.23–2.99).ConclusionsDespite contemporary care at high-volume centers, patients treated with VA-ECMO continue to have significant in-hospital morbidity and mortality. The optimization of outcomes will require refinements in patient selection and improvement of care delivery.     

Epithelium-dependent and -independent inhibitory effects of sivelestat, a neutrophil elastase inhibitor, on substance P-induced contraction of airway smooth muscle in lipopolysaccharide-treated guinea-pigs.

The underlying mechanism involved in the interaction between neutrophil elastase inhibitors and tachykinins has not been elucidated. In this study we have examined the effects of sivelestat, a neutrophil elastase inhibitor, on the in vitro responses of airways from lipopolysaccharide (LPS)-untreated or -treated guinea-pigs to substance P. Substance P (0.01-30 micromol/l) produced concentration-dependent contractions of both tracheal and bronchial ring preparations of LPS-untreated or -treated guinea-pigs. Responsiveness to substance P in these isolated airway preparations was augmented by either epithelium removal or LPS treatment. In epithelium-intact tracheal ring preparations isolated from LPS-untreated guinea-pigs, sivelestat (100 micromol/l) significantly inhibited substance P-induced contractions. The inhibitory action was markedly attenuated by pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l), and was almost undetected following removal of the epithelium. On the other hand, in bronchial ring preparations isolated from LPS-untreated guinea-pigs, sivelestat had only a very slight effect on substance P-induced contraction of the epithelium-intact preparation, whereas sivelestat greatly inhibited contraction in epithelium-removed bronchial ring preparations. In LPS-treated guinea-pigs, whether the epithelium was intact or not, sivelestat significantly inhibited the substance P-induced contraction of bronchial ring preparations. Pretreatment with L-NAME (100 micromol/l) or indomethacin (2 micromol/l) did not affect the inhibitory effect of sivelestat in bronchial ring preparations. In conclusion, epithelium removal or LPS treatment induced hyperreactivity to substance P in the guinea-pig airway. Sivelestat caused epithelium-, nitric oxide- and prostaglandin-dependent inhibition of the substance P-induced contraction of isolated guinea-pig tracheal ring preparations. In contrast, the inhibitory effect of sivelestat on substance P-induced contraction of guinea-pig bronchial ring preparations is mediated by epithelium-, nitric oxide- and prostaglandin-independent mechanisms. Sivelestat may be effective in reducing the airway hyperresponsiveness to tachykinins induced by epithelial injury as occurs in LPS-mediated inflammatory lung diseases.     

Coronary artery bypass grafting with combined arterial grafts

Coronary artery bypass grafting with combined arterial graft using the left internal mammary artery (IMA), right IMA, and the right gastroepiploic artery (GEA) was performed in 45 patients with saphenous vein graft (SVG) (29 patients) or without SVG (16 patients) from February 1989 to October 1989. The left IMA was used in all patients, the right IMA was used in 9 patients, and the GEA was used in 43 patients. Perioperative myocardial infarction was noted in two patients who had hospital deaths. Reopening the chest for postoperative bleeding was performed in two patients, and the cerebral accident was noted in one patient. Fourteen patients were operated on without the requirement for blood transfusion. Studied within 3 postoperative months, all arterial grafts were patent though the patency was 97.7% (43/44) in SVG. It is concluded that the combined arterial graft utilizing the IMAs and GEA can be used safely and effectively.     

The analysis of lymphocyte surface receptors recognized by wheat germ agglutinin for negative regulation of immune responses in cancer patients

The population of peripheral blood lymphocytes expressing surface receptors for a lectin, wheat germ agglutinin (WGA), which has been shown to recognize the same receptors as the soluble immune suppressor factor (SISF) elaborated from suppressor cells on the lymphocyte surface, was analyzed by using fluorescein isothiocyanate-conjugated WGA on flow cytometry in cancer patients. It was found that the populations of WGA+ lymphocytes in cancer patients were significantly higher than those in either normal volunteers or patients with benign disease and increased with progress of the tumor. The populations decreased after treatment in patients who underwent curative resection of the tumor and in responders of immunochemotherapy but not in those who received non-curative surgery or in non-responders. It was suggested that the increase of receptors for SISF on the lymphocyte surface might play an important role in the negative regulation of immune responses in cancer patients and that WGA might be a useful parameter for immunosuppression.     

Reduced Expression of nm23 Is Associated with Metastasis of Human Gastric Carcinomas

Reduced expression of nm23 gene is implicated in high metastatic potential In a variety of malignancies. To elucidate the role of nm23 in human gastric carcinomas, we examined loss of heterozygosity (LOH) of nm23 gene by Southern blotting, nm23 mRNA expression by Northern blotting and nm23 protein expression by Western blotting as well as immunohistochemistry in both primary and metastatic tumors. LOH of nm23 gene was found in 2 (8%) out of the 23 informative gastric carcinomas. Twenty-two (84%) out of the 26 cases expressed nm23 mRNA at higher levels in primary tumor tissue than in corresponding non-neoplastic mucosa. No obvious correlation was observed between clinico-pathological features and LOH of nm23 gene or nm23 mRNA expression. On the other hand, 52% of the gastric carcinomas showed reduction of nm23 immunoreactivity in the metastatic tumor of regional lymph nodes, as compared to the primary tumor. Interestingly, 71% of the gastric carcinomas showed weaker nm23 immunoreactivity in the liver metastasis than in the primary tumor. These results suggest that nm23 overexpression is linked with development of gastric carcinomas and the decrease in expression of nm23 participates in metastasis.