Bindu Akkanti

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

SUMMARY Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer.

Inhibition of Hyaluronan Synthesis Attenuates Pulmonary Hypertension Associated with Lung Fibrosis

Group III pulmonary hypertension (PH) is a highly lethal and widespread lung disorder that is a common complication in idiopathic pulmonary fibrosis (IPF) where it is considered to be the single most significant predictor of mortality. While increased levels of hyaluronan have been observed in IPF patients, hyaluronan‐mediated vascular remodelling and the hyaluronan‐mediated mechanisms promoting PH associated with IPF are not fully understood.

Prolonged venovenous extracorporeal membrane oxygenation in a patient with acute respiratory distress syndrome

A 30 year-old Hispanic man with no significant previous medical history presented with refractory hypoxemia after flu-like symptoms. Because of progressive hypoxemia despite appropriate ventilator strategies, venovenous extracorporeal membrane oxygenation (VV-ECMO) was initiated for severe acute respiratory distress syndrome (ARDS). His course was complicated at our hospital by subarachnoid hemorrhage, right ventricular failure, multiple pneumothoraces, and significant deconditioning. He was able to be weaned off VV-ECMO after 193 days and was ambulatory at discharge from the hospital.

Simultaneous left ventricular assist device placement and laparoscopic sleeve gastrectomy as a bridge to transplant for morbidly obese patients with severe heart failure

From the Department of Surgery, University of Texas Medical School at Houston, Houston, Texas; Division of Critical Care, Pulmonary and Sleep, University of Texas Medical School at Houston, Houston, Texas; Center for Advanced Heart Failure, University of Texas Medical School at Houston, Houston, Texas; and the Michael E. DeBakey Institute for Comparative Cardiovascular Science and Biomedical Devices, Texas A&M University, College Station, Texas.

Ventricular assist devices and sleep-disordered breathing

Congestive heart failure is one of the leading causes of morbidity and mortality in the United States, and left ventricular assist devices have revolutionized treatment of end-stage heart failure. Given that sleep apnea results in significant morbidity in these patients with advanced heart failure, practicing sleep physicians need to have an understanding of left ventricular assist devices. In this review, we summarize what is known about ventricular assist devices as they relate to sleep medicine.

Cardiac sarcoidosis presenting as arrhythmogenic right ventricular cardiomyopathy/dysplasia with ventricular aneurysms: a case report

A 70-year old Caucasian man with recurrent ventricular tachycardia and progressive biventricular failure attributed to arrhythmogenic right ventricular cardiomyopathy/dysplasia was evaluated for heart transplantation. Cardiac ventriculography revealed an abnormal left ventricle with five saccular aneurysms. Heart transplantation was performed. Pathology of the explanted heart showed multifocal sarcoid granulomas. Replacement fibrosis was widespread in both ventricles and associated with saccular aneurysms. No genetic basis was identified. Thus, the evidence suggested progressive cardiac sarcoidosis caused this patients unusual condition.

CT Imaging of Complications Associated with Continuous-Flow Left Ventricular Assist Devices (LVADs)

Heart failure is becoming increasingly prevalent, and more patients are being treated with left ventricular assist devices (LVADs), either as a bridge to transplant or as destination therapy. The use of continuous-flow LVADs is on the rise. LVAD therapy is associated with several classes of complications, including bleeding, thrombosis, and infection. CT imaging can be used effectively to diagnose LVAD complications, including mediastinal hematomas and pericardial, abdominal wall, and retroperitoneal hemorrhage, inflow and outflow graft and aortic thrombi, and driveline and pump pocket infections. CT can also be helpful in cases of device malfunction and can detect outflow graft kinking and inflow cannula misalignment. When interpreting CT scans in patients with LVADs, accessory materials implanted with the device should not be mistaken for hemorrhage or calcification. With training in recognizing LVAD complications, radiologists can play an important role in the evaluation of patients with heart failure.

Intra-pericardial use of recombinant factor VIIa in a patient with acute hemorrhagic pericardial effusion following transcutaneous aortic valve replacement-a case report

Perioperative bleeding can be a serious life-threatening complication in adult patients undergoing cardiac surgery, given the older age and additional comorbidities present in this patient population. The standard treatment options include transfusion of blood components and surgical re-exploration. We report the first case of an elderly female patient treated with local administration of recombinant factor VIIa (rFVIIa) for intractable hemorrhagic pericardial effusion, which developed following a transcutaneous aortic valve replacement (TAVR) procedure for severe aortic stenosis. No thromboembolic phenomena or adverse effects were observed. Local administration of rFVIIa is an efficacious treatment option for cardiac surgery patients as opposed to systemic administration of rFVIIa, use of massive blood products, or surgical re-exploration.

144: OBESITY PARADOX IN PATIENTS UNDERGOING VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION SUPPORT

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) transplantation (HT). We sought to characterize outcomes for these children. Methods: Retrospective review of HT patients in our pediatric referral hospital between 1995 and 2015. Inclusion criteria were all patients cannulated to ECMO within the first 7 days after HT. Demographics and risk factors were compared between survivors and non-survivors. Standard statistical methods were applied. Results: There were 246 HT performed in the study period. Congenital heart disease (CHD) and cardiomyopathy (CM) patients were evenly represented (119, 48% vs 115, 47%). ECMO was instituted within 7 days of transplant for 28 patients (11%), 18 (64%) of whom survived to hospital discharge. CHD was the most common indication for HT in those managed with early ECMO (18, 64% vs 10, 36% CM). Median time to ECMO was 1 day (range 0-2 days), with 11 patients (61%) cannulated to ECMO from cardio-pulmonary bypass in the operating room. Survival to hospital discharge did not differ according to patient factors such as age, weight, gender, pre-transplant diagnosis, liver or renal function, panel reactive antibody level or pre-transplant pulmonary vascular resistance. Transplant factors such as donor:recipient weight ratio and organ ischemic time were not associated with survival, nor was indication for ECMO. Patients cannulated to ECMO in the operating room were less likely to survive to hospital discharge (4 of 11, 36%, p=0.02). Four patients treated with early ECMO received another ECMO run (4/28, 14%) at median time 55 days after decannulation (range 18 to 635 days). Conclusions: ECMO can be used to rescue children with early graft dysfunction after HT. It is associated with early mortality, with only 64% of supported patients surviving to hospital discharge. Cannulation to ECMO in the operating room may represent severe early graft failure and these patients were less likely to survive.

Acute eosinophilic pneumonia

We report the case of an 18-year-old woman who presented to an outside hospital in respiratory distress and was found to have pulmonary eosinophilia. She remained profoundly hypoxaemic despite maximal ventilatory strategies and underwent cannulation for veno-venous extra corporeal membrane oxygenation (ECMO). The respiratory failure improved with time, using corticosteroids, and the veno-venous ECMO helped in stabilisation of the patient in the setting of profound hypoxaemia.