Natalia O. Glebova

Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis.

Mitochondrial cytochrome c release and inositol (1,4,5) trisphosphate receptor (InsP3R)-mediated calcium release from the endoplasmic reticulum mediate apoptosis in response to specific stimuli. Here we show that cytochrome c binds to the InsP3R during apoptosis. Addition of 1 nM cytochrome c blocks calcium-dependent inhibition of InsP3R function. Early in apoptosis, cytochrome c translocates to the endoplasmic reticulum where it selectively binds InsP3R, resulting in sustained, oscillatory cytosolic calcium increases. These calcium events are linked to the coordinate release of cytochrome c from all mitochondria. Our findings identify a feed-forward mechanism whereby early cytochrome c release increases InsP3R function, resulting in augmented cytochrome c release that amplifies the apoptotic signal.

Heterogeneous Requirement of NGF for Sympathetic Target Innervation In Vivo

The neurotrophin nerve growth factor (NGF) plays a crucial role in the development of the sympathetic nervous system. In addition to being required for sympathetic neuron survival in vivo and in vitro, NGF has been shown to mediate axon growth in vitro. The role of NGF in sympathetic axon growth in vivo, however, is not clear because of its requirement for survival. This requirement can be circumvented by a concomitant deletion of Bax, a pro-apoptotic Bcl-2 family member, thus allowing an examination of the role of neurotrophins in axon growth independently of their function in cell survival. Here, we analyzed peripheral sympathetic target organ innervation in mice deficient for both NGF and Bax. In neonatal NGF-/-; Bax-/- mice, sympathetic target innervation was absent in certain organs (such as salivary glands), greatly reduced in others (such as heart), somewhat diminished in a few (such as stomach and kidneys), but not significantly different from control in some (such as trachea). At embryonic day 16.5, peripheral target sympathetic innervation was also reduced in NGF-/-; Bax-/- mice, with analogous variability for different organs. Interestingly, in some organs such as the spleen the precise location at which sympathetic axons become NGF-dependent for growth was evident. We thus show that NGF is required for complete peripheral innervation of both paravertebral and prevertebral sympathetic ganglia targets in vivo independently of its requirement for cell survival. Remarkably, target organs vary widely in their individual NGF requirements for sympathetic innervation.

Fenestrated endovascular repair of abdominal aortic aneurysms is associated with increased morbidity but comparable mortality with infrarenal endovascular aneurysm repair

OBJECTIVE A recent prospective study found that fenestrated endovascular abdominal aortic aneurysm (AAA) repair (FEVAR) was safe and effective in appropriately selected patients at experienced centers. As this new technology is disseminated to the community, it will be important to understand how this technology compares with standard endovascular AAA repair (EVAR). The goal of this study was to compare the outcomes of FEVAR vs EVAR of AAAs. METHODS The American College of Surgeons-National Surgical Quality Improvement Program database from 2005 to 2012 was queried for AAAs (International Classification of Diseases, Ninth Revision code 441.4). Patients were stratified according to procedure (FEVAR vs EVAR). A bivariate analysis was done to assess preoperative and intraoperative risk factors for postoperative outcomes. Thirty-day postoperative mortality and complication rates were described for each procedure type. Multivariable logistic regression was performed to assess the association between the type of procedure and the risk of postoperative complications. RESULTS A total of 458 patients underwent FEVAR and 19,060 patients underwent EVAR for AAA. Patients undergoing FEVAR were older (P = .02) and less likely to have a bleeding disorder (P = .046). Otherwise, the incidence of comorbidities in both groups was similar. FEVAR was associated with increased median operative time (156 vs 137 minutes; P < .001), and average postoperative length of stay (3.3 vs 2.8 days; P = .03). There was a statistically significant increase in overall complications (23.6% vs 14.3%; P < .001) and postoperative transfusions (15.3% vs 6.1%, P < .001) and trends toward increased cardiac complications (2.2% vs 1.3%; P = .09) and the need for dialysis (1.5% vs 0.8%; P = .08) in the FEVAR group. Mortality (2.4% vs 1.5%; P = .12) was not statistically different. On multivariable analysis, FEVAR remained independently associated with the need for postoperative transfusions when operative time was <75th percentile (adjusted odds ratio, 1.72; 95% confidence interval, 1.09-2.72; P = .02) as well as when operative time was >75th percentile for respective procedures (adjusted odds ratio, 5.33; 95% confidence interval, 3.55-8.00; P < .001). CONCLUSIONS Patients undergoing FEVAR are more likely than patients undergoing EVAR to receive blood transfusions postoperatively and are more likely to sustain postoperative complications. Although mortality was similar, trends toward increased cardiac and renal complications may suggest the need for judicious dissemination of this new technology. Future research with larger number of FEVAR cases will be necessary to determine if these associations remain.

Technical risk factors for portal vein reconstruction thrombosis in pancreatic resection

OBJECTIVE Vascular reconstruction can facilitate pancreas tumor resection, but optimal methods of reconstruction are not well studied. We report our results for portal vein reconstruction (PVR) for pancreatic resection and determinants of postoperative patency. METHODS We identified 173 patients with PVR in a prospective database of 6522 patients who underwent pancreatic resection at our hospital from 1970 to 2014. There were 128 patients who had >1 year of follow-up with computed tomography imaging. Preoperative, intraoperative, and postoperative factors were recorded. Patients with and without postoperative PVR thrombosis were compared by univariable, multivariable, and receiver operating characteristic curve analyses. RESULTS The survival of patients was 100% at 1 month, 88% at 6 months, 66% at 1 year, and 39% on overall median follow-up of 310 days (interquartile range, 417 days). Median survival was 15.5 months (interquartile range, 25 months); 86% of resections were for cancer. Four types of PVR techniques were used: 83% of PVRs were performed by primary repair, 8.7% with interposition vein graft, 4.7% with interposition prosthetic graft, and 4.7% with patch. PVR patency was 100% at 1 day, 98% at 1 month, 91% at 6 months, and 83% at 1 year. Patients with PVR thrombosis were not significantly different from patients with patent PVR in age, survival, preoperative comorbidities, tumor characteristics, perioperative blood loss or transfusion, or postoperative complications. They were more likely to have had preoperative chemotherapy (53% vs 9%; P < .0001), radiation therapy (35% vs 2%; P < .0001), and prolonged operative time (618 ± 57 vs 424 ± 20 minutes; P = .002) and to develop postoperative ascites (76% vs 22%; P < .001). Among patients who developed ascites, 38% of those with PVR thrombosis did so in the setting of tumor recurrence at the porta detected on imaging, whereas among patients with patent PVR, 50% did so (P = .73). Patients with PVR thrombosis were more likely to have had prosthetic graft placement compared with patients with patent PVRs (18% vs 2.7%; P = .03; odds ratio [OR], 7.7; 95% confidence interval [CI], 1.4-42). PVR patency overall was significantly worse for patients who had an interposition prosthetic graft reconstruction (log-rank, P = .04). On multivariable analysis, operative time (OR, 1.01; 95% CI, 1.01-1.02) and prosthetic graft placement (OR, 8.12; 95% CI, 1.1-74) were independent predictors of PVR thrombosis (C statistic = 0.88). CONCLUSIONS Long operative times and use of prosthetic grafts for reconstruction are risk factors for postoperative portal vein thrombosis. Primary repair, patch, or vein interposition should be preferentially used for PVR in the setting of pancreatic resection.

Readmissions after complex aneurysm repair are frequent, costly, and primarily at nonindex hospitals

OBJECTIVE Readmissions after complex vascular surgery are not well studied. We sought to determine the rate of readmission after thoracic and thoracoabdominal aortic aneurysm repair (TAA/TAAAR) at our institution and to identify risk factors for and costs of readmission. METHODS Using a prospectively collected institutional database in conjunction with a Maryland statewide database, we reviewed index admissions and early readmissions for all patients who underwent TAA/TAAAR between 2002 and 2013 at the Johns Hopkins Hospital. Only Maryland residents were included to capture readmissions to any Maryland hospital. RESULTS We identified 115 Maryland residents (58% men; mean age, 65 ± 1.2 years) undergoing TAA/TAAAR (57% open repair). Early readmissions were frequent and occurred in 29% of patients. Of the readmitted patients, 79% (P < .001) were not readmitted to the index hospital where their operation was performed. Readmitted patients were not significantly different from nonreadmitted patients in age, gender, race, aneurysm type, and index length of stay. They were not different in preoperative comorbidities (including coronary artery disease, diabetes mellitus, smoking, renal insufficiency, and pulmonary disease), postoperative neurologic, renal, and cardiovascular complications, or 30-day or 5-year mortality. Multivariable analysis showed that significant risk factors for readmission were open repair (odds ratio, 3.12; 95% confidence interval, 1.12-9.54; P = .03) and postoperative pneumonia (odds ratio, 4.31; 95% confidence interval, 1.28-15.4; P = .02). Readmitted patients had significantly lower average income compared with the nonreadmitted cohort (U.S.

Effect of Patching on Reducing Restenosis in the Carotid Revascularization Endarterectomy Versus Stenting Trial

62,000 ±

Drivers of readmissions in vascular surgery patients

4000 vs

Contributions of planned readmissions and patient comorbidities to high readmission rates in vascular surgery patients.

73,000 ±

Risk of Disease Progression in Patients with Moderate Asymptomatic Carotid Artery Stenosis: Implications of Tobacco Use and Dual Antiplatelet Therapy

3000; P = .04). Striking differences were seen between patients readmitted to the index hospital where the operation was performed, and those who were readmitted to a nonindex hospital: patients readmitted to the index hospital were readmitted mainly for aneurysm-related surgical issues, whereas patients readmitted to the nonindex hospital were readmitted for medical morbidities. An aneurysm-related intervention was required in 75% of patients readmitted to the index hospital vs in 9% of patients readmitted to the nonindex hospital. Readmissions to a nonindex hospital cost significantly less than to the index hospital (U.S.

Outcomes of arterial resection during pancreatectomy for tumor

20,000 ±