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Expression microarray identifies novel markers of free flap failure in a rat model
Mithani, Suhail K; Bluebond-Langner, Rachel; Rodriguez, Eduardo D
Clinical detection of free flap failure lacks sensitivity. Failure is likely accompanied by altered gene expression; however, a genomic approach that identifies potential biomarkers and therapeutic targets has not been described. This study identifies genetic RNA expression alterations via microarray in a free flap failure animal model. A free tissue transfer rat model based on the inferior epigastric vessels was utilized. After microscopic anastomosis, the vein was occluded and RNA extracted from flap tissue of failure and control groups. Gene expression of 3 experimental and control group samples was assessed with the Affymetrix GeneChip Rat 230 v2.0 microarray. Quantitative reverse transcription polymerase chain reaction was performed on RNA of genes identified on an additional 6 experimental and 7 control group flaps. Eight hundred ninety of 28,000 genes had greater than 2-fold expression differences between experimental and controls. Student t test and 2-way analysis of variance filtering with equal variance identified 53 genes with statistically significant differences. Hierarchical clustering by gene ontology identified 4 genes with likely involvement in failure pathogenesis: RT1 class II, locus Bb, secreted frizzled-related protein 1, platelet/endothelial cell adhesion molecule, and Claudin 5. Validation performed by quantitative reverse transcription polymerase chain reaction revealed statistically significant expression alterations in locus Bb, platelet/endothelial cell adhesion molecule, and Claudin 5 of the failure group. Utilizing expression thresholds for test positivity, venous occlusion was predicted with 100% sensitivity and 86% specificity. Three highly sensitive and specific novel genes predictive of flap failure from venous occlusion were identified with altered expression in an animal model.
PMID: 19692897
ISSN: 0148-7043
CID: 631232
Functional outcomes of posttraumatic lower limb salvage: a pilot study of anterolateral thigh perforator flaps versus muscle flaps
Rodriguez, Eduardo D; Bluebond-Langner, Rachel; Copeland, Carol; Grim, T Nicole; Singh, Navin K; Scalea, Thomas
BACKGROUND: Functional outcomes of lower extremity reconstruction compared with amputation have been evaluated. However, there are little comparative data among the different reconstructive options. With the recent increase in perforator flaps, we compared the functional outcomes of muscle and perforator flaps. METHODS: We conducted a retrospective review of 136 lower extremity trauma patients who underwent reconstruction with either a free muscle or perforator flap during a 7-year period. Forty-two of these patients completed the study. Patients answered the short musculoskeletal functional assessment form and supplemental questions. A physical therapist evaluated performance of physical tasks. Donor site sensation was measured with the pressure specified sensing device. Radiographic fracture union was evaluated by an orthopedic surgeon. RESULTS: Of the 42 patients enrolled, 20 had coverage with perforator flaps and 22 with muscle flaps. Quality of life and functional outcomes demonstrate no difference (p > 0.05). Ninety-three percent of patients would go through the limb salvage process to avoid amputation. Sensation at the donor site was diminished in all patients; however, the perforator flap donor site had more significant sensory loss (p = 0.005). Time to bony union (p = 0.51), union in the presence of infection (p = 0.85), and infection after flap (p = 0.87) was not related to flap type. CONCLUSION: Both muscle and perforator flaps provide vascularized coverage, which nourishes the fracture but muscle flaps pilfer a functional unit which may not be inconsequential in a patient trauma. This pilot study suggests that functional outcomes of perforator skin flaps are equal to muscle flaps and a larger prospective study is warranted.
PMID: 19430232
ISSN: 0022-5282
CID: 631262
Pathologic Findings in Patients With Ureteropelvic Junction Obstruction and Crossing Vessels
Richstone, Lee; Seideman, Casey A; Reggio, Ernesto; Bluebond-Langner, Rachel; Pinto, Peter A; Trock, Bruce; Kavoussi, Louis R
OBJECTIVES: To define the role of crossing vessels in the pathophysiology of ureteropelvic junction (UPJ) obstruction, we analyzed the relationship between the presence of crossing vessels and UPJ pathologic findings in patients undergoing laparoscopic pyeloplasty. The significance of crossing renal vessels in patients with UPJ obstruction is unclear. METHODS: We performed a retrospective analysis of 155 consecutive patients undergoing laparoscopic pyeloplasty. Pathologic specimens from the UPJ were evaluated in 95 patients. The presence or absence of crossing vessels was documented intraoperatively. The histopathologic findings allowed for categorization into 5 groups: group 1, normal ureteral tissue; group 2, chronic inflammation; group 3, smooth muscle hypertrophy, group 4, fibrosis; and group 5, smooth muscle atrophy. The pathologic findings between patients with and without crossing vessels were compared. RESULTS: Overall, crossing vessels were identified in 98 patients (63.2%). Of the 95 cases with specimens retrieved for histologic analysis, 65 had crossing vessels and 30 did not. The most common UPJ histologic finding in patients with crossing vessels was no intrinsic abnormality (43%). In contrast, this was seen in only 10% of patients without a crossing vessel. In the group without crossing vessels, chronic inflammation (40%) was the predominant histologic findings. Patients with a crossing vessel were less likely to have intrinsic histologic pathologic findings (P < .0003). CONCLUSIONS: Patients with crossing vessels and UPJ obstruction had no histologic abnormalities identified in 43% of cases. This finding implicates crossing vessels in the pathogenesis of select cases of UPJ obstruction and direct mechanical compression as the etiology of obstruction in these individuals
PMID: 19193425
ISSN: 1527-9995
CID: 95682
Predictable patterns of intracranial and cervical spine injury in craniomaxillofacial trauma: analysis of 4786 patients
Mithani, Suhail K; St-Hilaire, Hugo; Brooke, Benjamin S; Smith, Ian M; Bluebond-Langner, Rachel; Rodriguez, Eduardo D
BACKGROUND: Patients presenting with traumatic craniomaxillofacial fractures often have occult concomitant injuries. This study was designed to determine whether facial fracture patterns are associated with a particular constellation of concomitant head and neck injuries. METHODS: A retrospective review of 4786 consecutive patients diagnosed with maxillofacial fractures at a dedicated urban trauma center from 1998 to 2005 was conducted; maxillofacial fractures and cervical spine injuries were grouped by dividing the craniomaxillofacial skeleton and cervical spine into thirds. Univariate and multivariate logistic regression analyses were used to identify associations between facial fractures and other traumatic injuries. RESULTS: Among all patients with facial fractures, 461 (9.7 percent) also had cervical spine injuries and 2175 (45.5 percent) had associated head injuries. Fractures of the upper face were associated with increased likelihood of mid lower cervical spine injuries, severe intracranial injuries, and increased mortality rates. Unilateral mandible injuries were associated with an increased likelihood of having upper cervical spine injuries, whereas unilateral midface injuries were associated with basilar skull fractures and several intracranial injuries. Finally, bilateral midface injuries were associated with basilar skull fracture and death. CONCLUSIONS: Craniomaxillofacial fractures are commonly associated with head and cervical spine injuries that involve predictable patterns of force dispersion from the maxillofacial skeleton and transmission to the cranial vault and cervical spine. These results suggest that concomitant injuries should be investigated closely with distinct types of facial fractures.
PMID: 19337097
ISSN: 1529-4242
CID: 631272
Application of skeletal buttress analogy in composite facial reconstruction
Bluebond-Langner, Rachel; Rodriguez, Eduardo D
Reconstructive algorithms for composite craniofacial defects have focused on soft tissue flaps with or without bone grafts. However, volumetric loss over time limits long-term preservation of facial contour. Application of craniofacial skeletal buttress principles to high-energy trauma or oncologic defects with composite vascularized bone flaps restores the soft tissue as well as the buttresses and ultimately preserves facial contour. We conducted a retrospective review of 34 patients with craniofacial defects treated by a single surgeon with composite bone flaps at R Adams Cowley Shock Trauma Center and Johns Hopkins Hospital from 2001 to 2007. Data collected included age, sex, mechanism of injury, type of defect, type of reconstructive procedures, and outcome. Thirty-four patients with composite tissue loss, primarily males (n = 24) with an average age of 37.4 years, underwent reconstruction with vascularized bone flaps (28 fibula flaps and 6 iliac crest flaps). There were 4 cranial defects, 8 periorbital defects, 18 maxillary defects, and 4 maxillary and periorbital defects. Flap survival rate was 94.1% with an average follow-up time of 20.5 months. Restoration of facial height, width, and projection is achieved through replacement of skeletal buttresses and is essential for facial harmony. Since 2001, our unit has undergone a paradigm shift with regard to treatment of composite oncologic and traumatic defects, advocating vascularized bone flaps to achieve predictable long-term outcomes.
PMCID:3052649
PMID: 22110793
ISSN: 1943-3875
CID: 631302
Facial subunit composite tissue allografts in nonhuman primates: I. Technical and immunosuppressive requirements for prolonged graft survival
Barth, Rolf N; Bluebond-Langner, Rachel; Nam, Arthur; Stanwix, Matthew; Shipley, Steven; Bartlett, Stephen T; Rodriguez, Eduardo D
BACKGROUND: Widespread application of composite tissue allotransplantation has been impeded by risks of rejection and conventional immunosuppression. The authors have developed a nonhuman primate composite tissue allotransplantation model that demonstrated reliable and long-term success necessary to progress to preclinical studies. METHODS: Composite facial subunits (e.g., skin, muscle, and bone) were transplanted between mismatched cynomolgus monkeys. Vascular supply was based on the common carotid artery and external and internal jugular veins. Facial allografts were heterotopically transplanted to the recipient's lower abdomen with end-to-side anastomoses of the common carotid artery to the common femoral artery and of both the internal and external jugular veins to the common femoral vein. Animals received tacrolimus monotherapy. Grafts were inspected daily, submitted to biopsy regularly, and studied with magnetic resonance imaging. RESULTS: Thirteen transplants were performed. Two grafts based on the common carotid artery and only the internal jugular vein failed within 3 to 5 days because of venous thrombosis not related to rejection. Subsequent transplants included anastomoses of both the internal and external jugular veins to the common femoral vein without thromboses. Immunosuppression consisted of tacrolimus monotherapy and was tolerated without complications. Long-term success was achieved with rejection-free graft survival (60 to 177 days). CONCLUSIONS: The authors have developed the first successful model of facial composite tissue allotransplantation in a nonhuman primate. Technical requirements include preservation of both internal and external jugular venous outflow. Tacrolimus monotherapy permitted prolonged rejection-free graft survival without early complications. This model provides a platform for further investigation of composite tissue allotransplantation tolerance and requirements for indefinite survival.
PMID: 19182606
ISSN: 1529-4242
CID: 631312
Frontal bandeau reconstruction with a fibula flap in a patient with Freeman-Sheldon syndrome [Case Report]
Bluebond-Langner, Rachel; Zamani, Amir; Rodriguez, Eduardo D
A 29-year-old woman with Freeman-Sheldon syndrome had a history of recurrent frontal sinus infections for which she underwent a 1-stage frontal sinus obliteration and cranioplasty using a free fibula osteocutaneous flap. This case is unique in that a free fibula flap had never been used to obliterate the frontal sinus in a patient with Freeman-Sheldon syndrome, nor had it been harvested from a limb with a clubfoot.
PMID: 19165042
ISSN: 1049-2275
CID: 631322
Horizontal maxillary osteotomy with interpositional fibula flap
Bluebond-Langner, Rachel; Witkin, Lisa R; Rodriguez, Eduardo D
Horizontal maxillary osteotomy with an interpositional fibula flap for maxillary deficiency offers several advantages over conventional techniques for maxillary reconstruction. Maxillary deficiencies in all 3 planes, vertical, anterior-posterior, and transverse, can be corrected with a long-term stable construct while simultaneously restoring bony and soft tissue deficiencies. We conducted a retrospective review of patients with maxillary hypoplasia who underwent Horizontal maxillary osteotomy with interpositional osteoseptocutaneous fibula flaps. Compared with nonvascularized bone grafts, vascularized bone flaps undergo less resorption and can be used in poorly vascularized, mechanically unstable, irradiated, or scarred wound beds.
PMID: 18812848
ISSN: 1049-2275
CID: 631352
Correction of the recalcitrant posttraumatic periorbital soft-tissue deformity: a novel microsurgical approach
Rodriguez, Eduardo D; Bluebond-Langner, Rachel; Devgan, Lara; Grant, Michael P; Iliff, Nicholas; Manson, Paul N
PMID: 18520884
ISSN: 1529-4242
CID: 631362
Maintenance of weight loss after body contouring surgery for massive weight loss
Shermak, Michele A; Bluebond-Langner, Rachel; Chang, David
BACKGROUND: Weight loss can be achieved through gastric bypass surgery or diet. Surgery has been reported to be more effective in achieving long-term weight loss. The authors aimed to determine whether massive weight loss is maintained or improved after body contouring. METHODS: Seventy patients underwent body contouring surgery after massive weight loss from January of 2001 to January of 2005. Data collected included age; gender; mode of massive weight loss; body mass index before massive weight loss, at contour surgery, and at follow-up; and weight of skin excised. RESULTS: Weight loss was achieved by open (n = 57) or laparoscopic gastric bypass surgery (n = 7), or by diet (n = 6). Average weight loss at contour surgery was 152 lb for open gastric bypass, 139 lb for laparoscopic gastric bypass, and 140 lb for the diet group. Mean weight of excised skin was 12.8 lb. Gastric bypass patients on average gained 2.3 lb, whereas nonsurgical patients gained 22 lb after body contouring, netting out skin excised. On multivariate analysis, weight loss did not differ between laparoscopic and open gastric bypass (p = 0.9); however, surgery led to a 27-lb greater weight loss compared with diet (p = 0.03). This effect was more remarkable with follow-up less than or equal to 18 months compared with more prolonged follow-up. Every year increase in age was associated with an 0.8-lb weight gain (p = 0.03). CONCLUSIONS: Gastric bypass surgery patients maintain massive weight loss better than "diet" patients. Weight loss tapers over time for gastric bypass surgery patients, with ultimate weight gain, comparable to that seen in the general population as it ages.
PMID: 18520903
ISSN: 1529-4242
CID: 2244092