Post-LT ARI or ARF occurred frequently in patients with normal preoperative renal function and was associated with both preoperative and intraoperative risk factors. Although both post-LT ARI and ARF are associated with significant post-LT morbidity, the impact of ARF is greater.
Complement factor H (CFH) is an important regulatory protein in the alternative pathway of the complement system, and CFH polymorphisms increase the genetic risk of age-related macular degeneration dramatically. These same human CFH variants have also been associated with dense deposit disease. To mechanistically study the function of CFH in the pathogenesis of these diseases, we created transgenic mouse lines using human CFH bacterial artificial chromosomes expressing full-length human CFH variants and crossed these to Cfh knockout (Cfh(-/-)) mice. Human CFH protein inhibited cleavage of mouse complement component 3 and factor B in plasma and in retinal pigment epithelium/choroid/sclera, establishing that human CFH regulates activation of the mouse alternative pathway. One of the mouse lines, which express relatively higher levels of CFH, demonstrated functional and structural protection of the retina owing to the Cfh deletion. Impaired visual function, detected as a deficit in the scotopic electroretinographic response, was improved in this transgenic mouse line compared with Cfh(-/-) mice, and transgenics had a thicker outer nuclear layer and less sub-retinal pigment epithelium deposit accumulation. In addition, expression of human CFH also completely protected the mice from developing kidney abnormalities associated with loss of CFH. These humanized CFH mice present a valuable model for study of the molecular mechanisms of age-related macular degeneration and dense deposit disease and for testing therapeutic targets.
VATS lobectomy in patients treated with induction therapy for locally advanced NSCLC is feasible and effective and does not appear to compromise oncologic outcomes.
Background
Salvage surgical resection for non-small cell lung cancer (NSCLC) patients initially treated with definitive chemotherapy and radiation can be performed safely, but the long-term benefits are not well characterized.
Methods
Perioperative complications and long-term survival of all patients with NSCLC who received curative-intent definitive radiation with or without chemotherapy followed by lobectomy from 1995-2012 were evaluated.
Results
During the study period, 31 patients met inclusion criteria. Clinical stage distribution was: stage I (n=2,6%); stage II (n=5,16%); stage IIIA (n=15,48%);stage IIIB (n=5,16%); stage IV (n=3,10%); and unknown (n=1,3%). The reasons surgery was initially not considered were: patients deemed medically inoperable (5 [16%]); extent of disease considered unresectable (21 [68%]); small cell lung cancer misdiagnosis (1 [3%]); and unknown (4 [13%]). Definitive therapy was radiation alone (n=2, 6%), concurrent chemoradiation (n=28, 90%), and sequential chemoradiotherapy (n=1, 3%). The median radiation dose was 60 Gy. Patients were subsequently referred for resection because of obvious local relapse, medical tolerance of surgery or post-therapy imaging suggested residual disease.Median time from radiation to lobectomy was 17.7 weeks.There were no perioperative deaths, and morbidity occurred in 15 (48%) patients. None of 3 patients with residual pathologic nodal disease survived longer than 37 months, but the 5-year survival of pN0 patients was 36%. Patients who underwent lobectomy for obvious relapse (n=3) also did poorly with median overall survival of 9 months.
Conclusion
Lobectomy after definitive radiation therapy can be done safely and is associated with reasonable long-term survival, particularly when patients do not have residual nodal disease.
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