Preclinical evidence has demonstrated anti-tumorigenic effects of metformin. The effects of metformin following pancreatic cancer, however, remain undefined. We sought to assess the association between metformin use and survival using a large, nationally representative sample of patients undergoing surgery for pancreatic cancer. Patients undergoing a pancreatic resection between January 01, 2010, and December 31, 2012, were identified using the Truven Health MarketScan database. Clinical data, including history of metformin use, as well as operative details and information on long-term outcomes were collected. Multivariable Cox proportional hazards regression analysis was performed to assess the effect of metformin use on overall survival (OS). A total of 3393 patients were identified. The mean age of patients was 54.2 years (SD = 9.1 years). Roughly one half of patients were female (n = 1735, 51.1 %); 49.1 % (n = 1665) presented with a Charlson comorbidity index of 3 or greater (CCI ≥3); and 19.6 % (n = 664) had diabetes. At the time of surgery, 60.0 % (n = 2034) of patients underwent a pancreaticoduodenectomy, 35.7 % (n = 1212) a partial/distal pancreatectomy, while 4.3 % (n = 147) had a total pancreatectomy. On pathology, 1057 (31.2 %) had lymph node metastasis. Metformin use was identified in 456 patients (13.4 %) and was more commonly administered among patients without locally advanced disease (14.3 vs. 11.6 %, p = 0.038). While OS was comparable between patients within the first year of surgery (OS at 1 year 65.4 % [95 % confidence interval (CI) 63.4-67.3 %] vs. 69.2 % [95 % CI 64.2-73.4 %]), patients who received metformin demonstrated an improved OS beginning at 18 months following surgery. On multivariable analysis adjusting for patient and clinicopathologic characteristics, metformin use was independently associated with a decreased risk of mortality (hazard ratio [HR] = 0.79, 95 % CI 0.67-0.93, p = 0.005). Metformin use was associated with an improved overall survival among patients undergoing pancreatic surgery for pancreatic cancer. Further work is necessary to better understand its role in modifying cancer-specific and overall health outcomes.

OBJECTIVES: Stroke is commonly reported in patients receiving venovenous extracorporeal membrane oxygenation, but risk factors are not well described. We sought to determine preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors for both ischemic and hemorrhagic strokes in patients with venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective analysis. SETTING: Data reported to the Extracorporeal Life Support Organization by 366 extracorporeal membrane oxygenation centers from 2013 to 2019. PATIENTS: Patients older than 18 years supported with a single run of venovenous extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 15,872 venovenous extracorporeal membrane oxygenation patients, 812 (5.1%) had at least one type of acute brain injury, defined as ischemic stroke, hemorrhagic stroke, or brain death. Overall, 215 (1.4%) experienced ischemic stroke and 484 (3.1%) experienced hemorrhagic stroke. Overall inhospital mortality was 36%, but rates were higher in those with ischemic or hemorrhagic stroke (68% and 73%, respectively). In multivariable analysis, preextracorporeal membrane oxygenation pH (adjusted odds ratio = 0.10; 95% CI, 0.03–0.35; p < 0.001), hemolysis (adjusted odds ratio = 2.27; 95% CI, 1.22–4.24; p = 0.010), gastrointestinal hemorrhage (adjusted odds ratio = 2.01; 95% CI 1.12–3.59; p = 0.019), and disseminated intravascular coagulation (adjusted odds ratio = 3.61; 95% CI, 1.51–8.66; p = 0.004) were independently associated with ischemic stroke. Pre-extracorporeal membrane oxygenation pH (adjusted odds ratio = 0.28; 95% CI, 0.12–0.65; p = 0.003), preextracorporeal membrane oxygenation Po 2 (adjusted odds ratio = 0.96; 95% CI, 0.93–0.99; p = 0.021), gastrointestinal hemorrhage (adjusted odds ratio = 1.70; 95% CI, 1.15–2.51; p = 0.008), and renal replacement therapy (adjusted odds ratio=1.57; 95% CI, 1.22–2.02; p < 0.001) were independently associated with hemorrhagic stroke. CONCLUSIONS: Among venovenous extracorporeal membrane oxygenation patients in the Extracorporeal Life Support Organization registry, approximately 5% had acute brain injury. Mortality rates increased two-fold when ischemic or hemorrhagic strokes occurred. Risk factors such as lower pH and hypoxemia during the pericannulation period and markers of coagulation disturbances were associated with acute brain injury. Further research on understanding preextracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation risk factors and the timing of acute brain injury is necessary to develop appropriate prevention and management strategies.

Objectives: Although acute brain injury (ABI) is common in patients receiving extracorporeal membrane oxygenation (ECMO), little is known regarding the mechanism and predictors of ischemic and hemorrhagic stroke. We aimed to determine the risk factors and outcomes of each ischemic and hemorrhagic stroke in patients with venoarterial (VA)-ECMO support.Design: Retrospective analysis.Setting: Data reported to the Extracorporeal Life Support Organization by 310 extracorporeal membrane oxygenation centers from 2013 to 2017.Patients: Patients more than 18 years old supported with a single run of VA-ECMO. Interventions: None.Measurements and Main Results: Of 10,342 V-A ECMO patients, 401 (3.9%) experienced ischemic stroke and 229 (2.2%) experienced hemorrhagic stroke.