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Complete surgical resection of pulmonary metastatic disease in patients with osteosarcoma is crucial to long‐term survival. Open thoracotomy allows palpation of nodules not identified on imaging but the impact on survival is unknown. The objective of this study was to compare overall survival (OS) and pulmonary disease‐free survival (DFS) in children who underwent thoracotomy vs thoracoscopic surgery for pulmonary metastasectomy. A multi‐institutional collaborative group retrospectively reviewed 202 pediatric patients with osteosarcoma who underwent pulmonary metastasectomy by thoracotomy (n = 154) or thoracoscopy (n = 48). Results were analyzed by Kaplan‐Meier survival estimates and multivariate Cox proportional hazard regression models. With median follow‐up of 45 months, 135 (67.5%) patients had a pulmonary relapse and 95 (47%) patients were deceased. Kaplan‐Meier analysis showed no significant difference in 5‐year pulmonary DFS (25% vs 38%; P = .18) or OS (49% vs 42%, P = .37) between the surgical approaches of thoracotomy and thoracoscopy. In Cox regression analysis controlling for other factors impacting outcome, there was a significantly increased risk of mortality (HR 2.11; P = .027; 95% CI 1.09‐4.09) but not pulmonary recurrence (HR 0.96; P = .90; 95% CI 0.52‐1.79) with a thoracoscopic approach. However, in the subset analysis limited to patients with oligometastatic disease, thoracoscopy had no increased risk of mortality (HR 1.16; P = .62; 0.64‐2.11). In conclusion, patients with metastatic osteosarcoma and limited pulmonary disease burden demonstrate comparable outcomes after thoracotomy and thoracoscopy for metastasectomy. While significant selection bias in these surgical cohorts limits the generalizability of the conclusions, clinical equipoise for a randomized clinical trial in patients with oligometastatic disease is supported.

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The incidence and prevalence of inflammatory bowel disease (IBD) are increasing worldwide. IBD is known to be multifactorial, but inflammatory signaling within the intestinal epithelium and a subsequent failure of the intestinal epithelial barrier have been shown to play essential roles in disease pathogenesis. CaMKIV is a multifunctional protein kinase associated with inflammation and cell cycle regulation. CaMKIV has been extensively studied in autoimmune diseases, but a role in idiopathic intestinal inflammation has not been described. In this study, active CaMKIV was highly expressed within the intestinal epithelium of humans with ulcerative colitis and wild-type (WT) mice with experimental induced colitis. Clinical disease severity directly correlates with CaMKIV activation, as does expression of proinflammatory cytokines and histologic features of colitis. In WT mice, CaMKIV activation is associated with increases in expression of 2 cell cycle proarrest signals: p53 and p21. Cell cycle arrest inhibits proliferation of the intestinal epithelium and ultimately results in compromised intestinal epithelial barrier integrity, further perpetuating intestinal inflammation during experimental colitis. Using a CaMKIV null mutant mouse, we demonstrate that a loss of CaMKIV protects against murine DSS colitis. Small molecules targeting CaMKIV activation may provide therapeutic benefit for patients with IBD.-Cunningham, K. E., Novak, E. A., Vincent, G., Siow, V. S., Griffith, B. D., Ranganathan, S., Rosengart, M. R., Piganelli, J. D., Mollen, K. P. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation contributes to the pathogenesis of experimental colitis via inhibition of intestinal epithelial cell proliferation.

<b>Introduction:</b> Extracorporeal Membrane Oxygenation (ECMO) is used in selected patient with cardiogenic and/or re- spiratory shock. We report our experience with standardized management protocols and the application of the Qua- droxD oxygenator with a centrifugal pump to maximize end-organ recovery and improve survival. <b>Methods:</b> This is an Internal Review Board (IRB) approved, single institution retrospective study of end-organ recovery and survival in pa- tients who required ECMO for cardiogenic and/or respiratory shock between July 2010 and June 2011. <b>Results:</b> Sixteen patients (median age: 46 years) were initiated on either Veno-Arterial (VA) or Veno-Venous (VV) ECMO. Cardiogenic shock, acute respiratory distress syndrome (ARDS) and a combined respiratory and cardiogenic compromise were the primary indications for ECMO in 8 (50%), 5 (31%) and 3 (19%) patients respectively. The median time on ECMO was 8 days (range: 4 - 26 days). Twelve patients (75%) were successfully weaned off ECMO, of which four (25%) were bridged to a ventricular assist device (VAD) and eight (50%) were weaned to recovery. All eight patients (100%) that were weaned to recovery and two patients (50%) that were bridged to a VAD were successfully discharged from the hospital, resulting in a discharge rate of 63%. There was an improvement in pre- vs. post-ECMO AST (449 IU/L vs. 63 IU/L, p < 0.05) in 5 patients (31%) with liver injury; serum lactate (9.1 mmol/L vs. 1.9 mmol/L, p < 0.05) in 8 patients (50%); and PaO2/FiO2 ratio (87 to 161, p = 0.01) in 10 patients (62%) with ARDS. Patients with evidence of pulmonary edema (n = 8. 50%) and ARDS (n = 8, 50%) on chest X-ray showed radiographic evidence of complete resolution. Renal function was preserved in 15 patients (94%). <b>Conclusion:</b> ECMO using the QuadroxD oxygenator and a centrifugal pump, coupled with standardized management protocols is beneficial in carefully selected patients. Improvement or main- tenance of end-organ function is associated with successful bridge to device therapy and/or increased survival