Nelson H. Goldberg

Acute-Phase Serum Amyloid A: An Inflammatory Adipokine and Potential Link between Obesity and Its Metabolic Complications

Background Obesity is associated with low-grade chronic inflammation, and serum markers of inflammation are independent risk factors for cardiovascular disease (CVD). However, the molecular and cellular mechanisms that link obesity to chronic inflammation and CVD are poorly understood. Methods and Findings Acute-phase serum amyloid A (A-SAA) mRNA levels, and A-SAA adipose secretion and serum levels were measured in obese and nonobese individuals, obese participants who underwent weight-loss, and persons treated with the insulin sensitizer rosiglitazone. Inflammation-eliciting activity of A-SAA was investigated in human adipose stromal vascular cells, coronary vascular endothelial cells and a murine monocyte cell line. We demonstrate that A-SAA was highly and selectively expressed in human adipocytes. Moreover, A-SAA mRNA levels and A-SAA secretion from adipose tissue were significantly correlated with body mass index ( r = 0.47; p = 0.028 and r = 0.80; p = 0.0002, respectively). Serum A-SAA levels decreased significantly after weight loss in obese participants ( p = 0.006), as well as in those treated with rosiglitazone ( p = 0.033). The magnitude of the improvement in insulin sensitivity after weight loss was significantly correlated with decreases in serum A-SAA ( r = −0.74; p = 0.034). SAA treatment of vascular endothelial cells and monocytes markedly increased the production of inflammatory cytokines, e.g., interleukin (IL)-6, IL-8, tumor necrosis factor alpha, and monocyte chemoattractant protein-1. In addition, SAA increased basal lipolysis in adipose tissue culture by 47%. Conclusions A-SAA is a proinflammatory and lipolytic adipokine in humans. The increased expression of A-SAA by adipocytes in obesity suggests that it may play a critical role in local and systemic inflammation and free fatty acid production and could be a direct link between obesity and its comorbidities, such as insulin resistance and atherosclerosis. Accordingly, improvements in systemic inflammation and insulin resistance with weight loss and rosiglitazone therapy may in part be mediated by decreases in adipocyte A-SAA production.

Revascularization of human acellular dermis in full-thickness abdominal wall reconstruction in the rabbit model.

This study investigates whether human acellular dermis (Alloderm; LifeCell, Branchburg, NJ) revascularizes when used to reconstruct abdominal wall defects in rabbits. This could prove useful in infected situations in which prosthetic mesh is suboptimal. Twenty-five rabbits were randomly assigned to one of three groups: primary closure (n = 5), expanded polytetrafluoroethylene (GoreTex; W.L. Gore, Flagstaff, AZ) repair (n = 10), or AlloDerm (LifeCell) repair (n = 10). The rabbits in the primary closure group received a 7 cm × 0.5 cm full-thickness abdominal wall defect that was closed primarily. A 7 cm × 3 cm full-thickness abdominal wall defect was created in the other two groups. The defects were repaired with a GoreTex Mycromesh (W.L. Gore), or AlloDerm (LifeCell) patch. At 30 days, the following endpoints were evaluated: (1) incidence of herniation; (2) presence of intra-abdominal adhesions; (3) the breaking strength of the patch–fascial interface; and (4) evaluation of graft vascularization by fluorescein dye infusion and histological analysis. There was no incidence of herniation in any of the rabbits. Visceral adhesions to the patch were found in all animals in the Gore-Tex (W.L. Gore) group but in none in the AlloDerm (LifeCell) group. The size of the patch was unchanged in all the rabbits except for two rabbits in the AlloDerm (LifeCell) group that stretched 1 cm in the transverse dimension. The change in size was not statistically significant (p = 0.17) when compared with the change in size in the Gore-Tex (W.L. Gore) group. The mean breaking strength of the primary closure group was significantly higher (521.2 N/mm2 ± 223.0) than that of the two patch-repair groups (p < 0.05). But there was no significant difference between the mean breaking strength of the AlloDerm (LifeCell) fascial interface (288.6 N/mm2 ± 97.1 SD) and that of the Gore-Tex (W.L. Gore) fascial interface (337.0 N/mm2 ± 141.2). Fluorescein dye infusion and histological analysis confirmed vascularization of the AlloDerm (LifeCell) graft. This study demonstrates that AlloDerm (LifeCell) does become vascularized when used as a fascial interposition graft for abdominal wall reconstruction. AlloDerm (LifeCell) also performs mechanically as effectively as Gore-Tex (W.L. Gore) in ventral hernia repair at 1 month after operation in the rabbit model.

Restoring abdominal wall integrity in contaminated tissue-deficient wounds using autologous fascia grafts

&NA; Necrotizing abdominal wall infections, enteric fistulae, or exposed prosthetic material after ventral hernia repair often results in a loss of abdominal wall integrity. Further surgical reconstruction with prosthetic material is usually contraindicated in the contaminated wound because of the high infection rate necessitating prosthetic removal and further abdominal wall debridement. Consequently, for the past 9 years, we have been using free grafts of autologous fascia lata to replace deficient abdominal wall fascia and muscle in situations where prosthetic material is contraindicated and local tissue rearrangement (i.e., component separation) would be inadequate. Thirty‐two patients (mean age 59 years) underwent abdominal wall reconstruction with autologous fascia lata grafts. Indications included exposed mesh (31 percent), enteric fistulae (28 percent), enteric contamination (22 percent), wound infection (13 percent), and immunosuppression alone (6 percent); 31 percent of all patients were immunosuppressed secondary to either a solid organ transplant or a systemic inflammatory disorder. Fascia grafts (mean size 10 × 17 cm) were sutured to the surrounding abdominal wall and covered by local skin flap advancement and/or myocutaneous flap rotation. All abdominal reconstructions were initially successful. Subsequent local abdominal wall complications included cellulitis (n = 3), seroma (n = 2), and skin dehiscence with exposed fascia grafts (n = 7). Five of seven patients with skin dehiscence healed by secondary intention, whereas two had split‐thickness skin grafts successfully applied to the granulating fascia. Thigh donor site complications included hematoma (n = 1), skin dehiscence (n = 1), and seroma (n = 2). There have been no cases of lateral knee instability. The average follow‐up period is 27 months (range 3 to 106 months). Recurrent hernia has been seen in three patients (9 percent). Interestingly, laparotomy has been performed through an intact fascia lata patch in three patients for unrelated intra‐abdominal conditions. In each case, the graft was intact and revascularized, confirming experimental animal data performed in our laboratory. Recurrent hernia has not been observed through the laparotomy site. Our 9‐year experience has demonstrated that in the face of large, contaminated abdominal wounds where prosthetic material is contraindicated and local tissue rearrangement would be inadequate, fascia lata autografts are a reliable adjuvant to abdominal wall reconstruction.

Efficacy of Operative Cure in Pressure Sore Patients

The advent of air flotation—type beds and purified growth factors that may accelerate open wound contraction, coupled with very high recurrence rates and decreasing health resources, suggests that surgical reconstruction of pressure sores may not be indicated in all patients. In an effort to define which patients might benefit from operation, we reviewed the data from 40 consecutive patients with 68 pressure sores operated on under the direction of a single surgeon between 1981 and 1989. Patients were categorized on the basis of the presence or absence of paraplegia and its etiology. Sixty-six operations were performed, 55 muscle or fasciocutaneous flaps and 11 cutaneous flaps. There was a 36 percent operative complication rate, with no operative mortalities. Follow-up ranged from 1 to 71 months, with a mean of 21 months. Despite an 80% healed rate at the time of discharge, 61% of sores and 69% of patients had recurrent ulceration within a mean of 9.3 months. Analysis of these data indicates that surgical reconstruction of pressure sores does not appear to be efficacious in young posttraumatic paraplegics or cerebrally compromised elderly patients. Further review of the data failed to identify those patients likely to remain healed after operative repair of their pressure sores.

What is the best surgical margin for a Basal cell carcinoma: a meta-analysis of the literature.

Background: Current management of basal cell carcinoma is surgical excision. Most resections use predetermined surgical margins. The basis of ideal resection margins is almost completely from retrospective data and mainly from small case series. This article presents a systematic analysis from a large pool of data to provide a better basis of determining ideal surgical margin. Methods: A systematic analysis was performed on data from 89 articles from a larger group of 973 articles selected from the PubMed database. Relevant inclusion and exclusion criteria were applied to all articles reviewed and the data were entered into a database for statistical analysis. Results: The total number of lesions analyzed was 16,066; size ranged from 3 to 30 mm (mean, 11.7 ± 5.9 mm). Surgical margins ranged from 1 to 10 mm (mean, 3.9 ± 1.4 mm). Negative surgical margins ranged 45 to 100 percent (mean, 86 ± 12 percent). Recurrence rates for 5-, 4-, 3-, and 2-mm surgical margins were 0.39, 1.62, 2.56, and 3.96 percent, respectively. Pooled data for incompletely excised margins have an average recurrence rate of 27 percent. Conclusions: A 3-mm surgical margin can be safely used for nonmorpheaform basal cell carcinoma to attain 95 percent cure rates for lesions 2 cm or smaller. A positive pathologic margin has an average recurrence rate of 27 percent.

Recalcitrant abdominal wall hernias: long-term superiority of autologous tissue repair.

Secondary repair of recurrent ventral hernia is difficult, and success depends on re-establishing the functional integrity of the abdominal wall. Current techniques used for closure of these defects have documented recurrence rates as high as 54 percent. The authors’ 8-year experience utilizing variations of the components separation technique for autologous tissue repair of recalcitrant hernias emphasizes that recurrent or recalcitrant hernias benefit from the creation of a dynamic abdominal wall. A total of 389 patients were retrospectively identified as having abdominal wall defects, and 284 of these patients met the selection criteria. Study patients were grouped according to the type of surgical repair used. The recurrence rate was 20.7 percent over all study groups and was directly related to the extent of repair required. Group 1 patients (wide tissue undermining) had a recurrence rate of only 15 percent, while in group 2 (complete components separation), the recurrence rate was 22 percent. Group 3 patients (interpositional fascia lata graft) had a 29 percent recurrence rate. Time to recurrence was also significantly different across treatment groups, with study group 3 experiencing earlier hernia recurrence. The most frequent postoperative complication was wound infection, which was directly related to the repair performed. The relative odds of recurrence versus the risk factors of age, sex, perioperative steroid use, wound infection, defect size, and the presence of enterocutaneous fistula were studied with a logistic regression analysis. These factors did not possess statistical significance for predicting hernia recurrence. The preoperative presence of mesh was independently significant for hernia recurrence, increasing the relative odds 2.2 times (p = 0.01). Similarly, when other risk factors were controlled for, increasing the complexity of the treatment group, from study group 1 (wide tissue undermining) to study group 3 (interpositional fascia lata graft), also increased the odds of hernia recurrence 1.5-fold per group (p = 0.04). Average inpatient cost was

Advantages of autologous fascia versus synthetic patch abdominal reconstruction in experimental animal defects.

24,488. The length of inpatient stay ranged from 2 to 172 days (average, 12.8 days). The length of inpatient stay and costs were directly related to the extent of repair required. Using the analysis of variance test for multiple factors, the presence of an enterocutaneous fistula (p = 0.0014) or a postoperative wound infection (p = 0.008) independently increased the length of inpatient stay and hospital costs. A total of 108 successfully repaired patients were contacted by telephone and agreed to participate in a self-reported satisfaction survey. The patients noticed improvements in the appearance of their abdomen, in their postoperative emotional state, and in their ability to lift objects, arise from a chair or a bed, and exercise. These results suggest that recalcitrant hernia defects should be solved, when possible, by reconstructing a dynamic abdominal wall.

Acellular Dermal Matrix Compared with Synthetic Implant Material for Repair of Ventral Hernia in the Setting of Peri-Operative Staphylococcus aureus Implant Contamination: A Rabbit Model

&NA; Although prosthetic patches (i.e., expanded polytetrafluoroethylene) are commonly used to repair abdominal fascial defects, autologous tissue is preferred in the presence of wound contamination. This study was undertaken to discover (1) whether fascial grafts are revascularized and incorporated as living tissue, and (2) whether fascial grafts are more resistant to bacterial contamination than prosthetic patches. In the first experiment, 18 New Zealand White rabbits underwent full‐thickness resection of the central abdominal wall preserving only panniculus carnosus and skin. Six control animals had only skin repaired, and all developed large ventral hernias. Twelve animals had the defect repaired with thoracodorsal fascia patches. At 3‐ and 6‐week intervals, no hernias were present and all patches were incorporated with minimal contraction. Fluorescein angiography verified revascularization from the surrounding abdominal wall. Next, 36 rabbits underwent similar resection followed by repair with either autologous fascia (n = 18) or expanded polytetrafluoroethylene (n = 17). Six rabbits of each repair group were inoculated with 104 Staphylococcus aureus and twelve rabbits with each repair were inoculated with 109 S. aureus. All rabbits receiving 104 S. aureus were infectionfree survivors. Seven of the twelve expanded polytetrafluoroethylene‐repaired animals receiving 109 S. aureus developed necrotizing wound infections and died. Only 2 of 12 rabbits with autologous fascia repairs died from wound sepsis and 1 died of diarrhea with a healed wound. Differences in wound infection rates achieved statistical significance, whereas survival differences approached significance (Fishers exact test), suggesting that revascularized fascial grafts may be more resistant to bacterial contamination than expanded polytetrafluoroethylene patches at this concentration (109 S. aureus). (Plast. Reconstr. Surg. 97: 801, 1996.)

Comparison of acellular dermal matrix and synthetic mesh for lateral chest wall reconstruction in a rabbit model.

BACKGROUND Implant infection is a common clinical complication of abdominal hernia repair. Our objectives were to determine if acellular dermal matrix (ADM) grafts resisted Staphylococcus aureus infection better (as measured by ability to reduce or clear bacterial counts) than synthetic (polytetrafluoroethylene [PTFE]) mesh when used in abdominal wall reconstruction, and to determine whether vascularization of the implant occurred. We hypothesized that the ability of the ADM grafts to vascularize and allow cellular ingrowth would allow the immune system to clear the infection better in these animals. METHODS In New Zealand White rabbits (average weight, 3.0 kg), a full-thickness 3 x 3 cm(2) abdominal defect was created, then repaired with an interpositional implant (ADM, n = 62; PTFE, n = 57). Before skin closure, the epidermal surface of each implant was inoculated with 1 mL of S. aureus at various concentrations (10(4) colony-forming units [CFU]/mL, n = 82; 10(6) CFU/mL, n = 27; 10(9) CFU/mL, n = 10), and the rabbits were harvested at either day 7 or day 21. RESULTS At day 7, ADM grafts inoculated with 10(4) CFU had lower counts or no bacteria (p = 0.006), fewer adhesions (p = 0.005), and fewer abscesses (p = 0.008) than PTFE grafts. By day 21, more ADM (n = 12) than PTFE (n = 0) grafts were free of bacteria (p = 0.002). Fewer rabbits with ADM grafts formed abscesses (13 vs. 19; p = 0.03). When evaluating the 7- and 21-day 10(4) CFU groups combined, a total of 15 rabbits with ADM cleared the bacteria completely vs. none of those with PTFE grafts (p < 0.001). There was no significant difference in bacterial counts or wound complications at days 7 or 21 between PTFE and ADM implants when inoculated with 10(6) CFU. All rabbits inoculated with 10(9) CFU died of sepsis within 48 h. Herniation did not occur in any of the animals. CONCLUSIONS Our study demonstrates that ADM resists surgical site infection caused by S. aureus in an animal model without compromising the ventral hernia repair. This ability of ADM grafts to perform well in the setting of infection is most likely attributable to their capacity to vascularize and aid clearance of bacteria.

Prevention of adriamycin-induced full-thickness skin loss using hyaluronidase infiltration

Background: Synthetic mesh is used for chest wall reconstruction, but infection or exposure can occur and necessitate removal. Human acellular dermal matrix (AlloDerm) has been used to reconstruct musculofascial defects in the trunk with low infection and herniation rates. AlloDerm may have advantages over synthetic mesh for chest wall reconstruction. This study compared outcomes and repair strengths of AlloDerm to expanded polytetrafluoroethylene mesh used for repair of rib cage defects. Methods: A 3 × 3-cm, full-thickness, lateral rib cage defect was created in each rabbit and repaired with expanded polytetrafluoroethylene (n = 8) or acellular dermal matrix (n = 9). At 4 weeks, the animals were euthanized and evaluated for lung herniation/dehiscence, strength of adhesions between the implant and intrapleural structures, and breaking strength of the implant materials and the implant-fascia interface. Tissue sections were analyzed with histologic and immunohistochemical staining to evaluate cellular infiltration and vascularization. Results: No herniation or dehiscence occurred with either material. The incidence and strength of adhesions was similar between materials. The mean breaking strength of the AlloDerm-fascia interface (14.5 ± 8.9 N) was greater than the expanded polytetrafluoroethylene–fascia interface (8.7 ± 4.4 N; p = 0.027) and similar to the rib-intercostal-rib interface of the contralateral native chest wall (14.0 ± 5.6 N). The AlloDerm grafts became infiltrated with cells and vascularized after implantation. Conclusions: AlloDerm used for chest wall reconstruction results in greater implant-defect interface strength than expanded polytetrafluoroethylene. The ability of AlloDerm to become vascularized and remodeled by autologous cells and to resist infection may be advantageous for chest wall reconstruction.