Christine H. Rohde

Electromagnetic fields as first messenger in biological signaling: Application to calmodulin-dependent signaling in tissue repair

BACKGROUND The transduction mechanism for non-thermal electromagnetic field (EMF) bioeffects has not been fully elucidated. This study proposes that an EMF can act as a first messenger in the calmodulin-dependent signaling pathways that orchestrate the release of cytokines and growth factors in normal cellular responses to physical and/or chemical insults. METHODS Given knowledge of Ca(2+) binding kinetics to calmodulin (CaM), an EMF signal having pulse duration or carrier period shorter than bound Ca(2+) lifetime may be configured to accelerate binding, and be detectable above thermal noise. New EMF signals were configured to modulate calmodulin-dependent signaling and assessed for efficacy in cellular studies. RESULTS Configured EMF signals modulated CaM-dependent enzyme kinetics, produced several-fold increases in key second messengers to include nitric oxide and cyclic guanosine monophosphate in chondrocyte and endothelial cultures and cyclic adenosine monophosphate in neuronal cultures. Calmodulin antagonists and downstream blockers annihilated these effects, providing strong support for the proposed mechanism. CONCLUSIONS Knowledge of the kinetics of Ca(2+) binding to CaM, or for any ion binding specific to any signaling cascade, allows the use of an electrochemical model by which the ability of any EMF signal to modulate CaM-dependent signaling can be assessed a priori or a posteriori. Results are consistent with the proposed mechanism, and strongly support the Ca/CaM/NO pathway as a primary EMF transduction pathway. GENERAL SIGNIFICANCE The predictions of the proposed model open a host of significant possibilities for configuration of non-thermal EMF signals for clinical and wellness applications that can reach far beyond fracture repair and wound healing.

The Breast: A Clean-Contaminated Surgical Site

BACKGROUND Capsular contracture is one of the most common complications associated with breast implants. While the cause of this process has not yet been elucidated, subclinical infection is a likely culprit. OBJECTIVES The authors assess the hypothesis that a probable source of contamination is endogenous breast bacteria, likely originating in the ducts themselves and most concentrated near the nipple. METHODS Twenty-five healthy patients presenting for routine reduction mammaplasty were recruited as study participants. Tissue samples were taken intraoperatively from the periareolar, inframammary, and axillary regions of each sampled breast. Specimens were then processed in the microbiology laboratory, and quantitative bacterial counts were obtained. RESULTS Of the 50 breasts sampled, 19 yielded positive culture results, for a rate of 38%. There was a significant difference in the positive culture rate among all three sites, with increasing quantitative bacterial counts in the axillary, inframammary, and periareolar regions, respectively. The most commonly-identified organisms in this study included various species of Staphylococcus and Propionibacterium acnes, with S. epidermidis being the most common. CONCLUSIONS The breast harbors significant endogenous bacteria that can become the source of spontaneous or postoperative infection. Positive intraoperative cultures with high quantitative counts suggest that breast tissue harbors more bacteria than normal skin flora. Routine perioperative antibiotic prophylaxis may be suboptimal for the prevention of foreign body seeding in this setting. Furthermore, bacterial concentrations are highest in areas with the most ductal tissue, namely the periareolar region. These findings may be helpful when considering which incision site to select for augmentation mammaplasty.

The ability of intra-operative perfusion mapping with laser-assisted indocyanine green angiography to predict mastectomy flap necrosis in breast reconstruction: A prospective trial

Mastectomy skin flap ischaemia leading to necrosis is a common occurrence. Laser-assisted indocyanine green (ICG) angiography can assist to locate these poorly perfused areas intra-operatively. Our study aims to identify specific perfusion values produced by ICG angiography that accurately predict mastectomy flap necrosis. A total of 42 patients undergoing autologous or implant-based breast reconstruction had mastectomy flaps imaged using laser-assisted ICG angiography at the completion of reconstruction. Intra-operative perfusion values were correlated with postoperative skin flap outcomes. Risk factors for abnormal perfusion were recorded and analysed. A total of 62 breast reconstructions were imaged, including 48 tissue expander reconstructions, six transverse rectus abdominis myocutaneous (TRAM) flaps, six deep inferior epigastric perforator (DIEP) flaps and two direct-to-implant reconstructions. Eight cases (13%) of full-thickness skin necrosis were identified postoperatively. A SPY Elite(®) value of ≤ 7 accurately predicted the development of flap necrosis at 88% sensitivity and 83% specificity. False-positive cases (those with perfusion values ≤ 7 which did not develop necrosis) were more likely to have a smoking history and/or to have had an epinephrine-containing tumescent solution used during mastectomy. Excluding patients with smoking or epinephrine use, a SPY value of ≤ 7 predicted flap necrosis with a sensitivity of 83% and specificity of 97%. Thus, these data suggest that laser-assisted ICG angiography predicts postoperative outcomes with high accuracy. In our series, a SPY value of ≤ 7 correlated well with mastectomy flap necrosis. Furthermore, smoking and intra-operative injections containing epinephrine should be considered when evaluating low perfusion values as they can lead to false-positive test results.

Mid-body contouring in the post-bariatric surgery patient

Background: Obesity has become an increasingly important health care problem. It is estimated that almost 20 percent of the adult U.S. population is obese, including approximately 5 percent of the population considered morbidly obese. Recent advances in bariatric surgery have improved the safety and efficacy of weight-loss operations. As a consequence of the above factors, there has been a 150 percent increase in the number of gastric bypass and vertical banding gastroplasty procedures performed over the past 3 years. Post–bariatric surgery care has become an integral part in the care of these patients, with plastic surgeons playing an important role. Methods: The senior author (B.S.) has developed unique variations of the circumferential and near-circumferential abdominoplasty operations to fulfill the needs of these patients. Seventy-five consecutive mid-body lift procedures have been performed over the past 5 years. The basic operation involves circumferential incisions, anterior flap undermining, and simultaneous flap thinning, without resorting to the need for an anterior midline incision. Results: A dramatic improvement in appearance results from the anterior resection and the lateral thigh and buttock lifts that this procedure affords. More recently, the lower back roll has been removed as well. A cohesive operative sequence that includes optimized patient preparation and positioning, tailoring of flaps for improved contour with avoidance of unnecessary midline scars, a strong superficial fascial system closure, and coordination with the entire operating room team has been developed. Conclusion: The procedure is associated with a low complication rate, a dramatically shortened operative time, and high patient satisfaction.

Bioengineering strategies to generate vascularized soft tissue grafts with sustained shape

Tissue engineering offers the possibility for soft tissue reconstruction and augmentation without autologous grafting or conventional synthetic materials. Two critical challenges have been addressed in a number of recent studies: a biology challenge of angiogenesis and an engineering challenge of shape maintenance. These two challenges are inter-related and are effectively addressed by integrated bioengineering strategies. Recently, several integrated bioengineering strategies have been applied to improve bioengineered adipose tissue grafts, including internalized microchannels, delivery of angiogenic growth factors, tailored biomaterials and transplantation of precursor cells with continuing differentiation potential. Bioengineered soft tissue grafts are only clinically meaningful if they are vascularized, maintain shape and dimensions, and remodel with the host. Ongoing studies have begun to demonstrate the feasibility towards an ultimate goal to generate vascularized soft tissue grafts that maintain anatomically desirable shape and dimensions.

Improving Access to Care: Breast Surgeons, the Gatekeepers to Breast Reconstruction

BACKGROUND Fewer than half of patients undergo reconstruction after breast cancer treatment, despite its quality of life benefits. Earlier studies demonstrated that most general surgeons do not discuss reconstructive options with patients. The aim of this study was to examine the likelihood of reconstruction within a cohort of mastectomy patients and compare rates of reconstruction between those referred and not referred for plastic surgery evaluation. STUDY DESIGN Retrospective review of the records of 471 consecutive patients between the ages of 19 and 94 years who underwent mastectomy between 2003 and 2007. Variables evaluated were age, body mass index, diabetes, laterality (unilateral vs bilateral), TNM staging, history of radiation, smoking history, insurance type, and race. RESULTS Of 471 patients, 313 were referred for consultation with a plastic surgeon and 158 were not; 91.7% of those referred were reconstructed and 100% of those not referred were not reconstructed. The 2 groups differed considerably in terms of age (mean age 61.84 years in the nonreferred group vs 51.83 years in the referred group), body mass index (25.9 in referred group, 27 in nonreferred group), diabetes (15% in nonreferred group vs 3.5% in referred group), and laterality (14% of nonreferred group underwent bilateral mastectomies vs 26% of those referred). The groups did not differ significantly in terms of race or tobacco use. Those with private insurance were more likely to be reconstructed, but no independent effect of insurance type was seen on multivariate analysis. CONCLUSIONS The breast surgeons decision to refer a patient for reconstruction significantly affects whether the patient will receive breast reconstruction. Factors that appear to influence the referral decision are age, diabetes, body mass index, and laterality of mastectomy (bilateral more than unilateral).

The absorbable dermal staple device: a faster, more cost-effective method for incisional closure.

Background: Closure with dermal sutures is time consuming, may increase the risks of inflammation and infection secondary to foreign body reaction, exposes the surgeon to possible needlestick injuries, and has variable cosmetic outcomes depending on each surgeons technique. The absorbable INSORB dermal stapler is hypothesized to be faster and more cost effective than sutures for dermal layer closures and provides a safer and more consistent result. Methods: This is a prospective, randomized, controlled study. Patients undergoing bilateral breast reconstruction with tissue expanders had one incision randomized to dermal closure with absorbable dermal staples. The contralateral side was closed with dermal sutures. During the expansion period, wounds were assessed by a blinded plastic surgeon using the 13-point Vancouver Scar Scale. At the time of implant exchange, both scars were excised and examined for histologic signs of inflammation. Results: Eleven patients (22 incisions) were enrolled in the study. The dermal stapler was four times faster than standard suture closure, reducing closure time by 10.5 minutes (p ≤ 0.001). Overall cost savings with the dermal stapler was

Gustilo grade IIIB tibial fractures requiring microvascular free flaps: external fixation versus intramedullary rod fixation.

220 per case. In the early postoperative period, the dermal stapler had a higher Vancouver Scar Scale score than sutures because of superior wound eversion, a beneficial characteristic for wound healing. By 4 months postoperatively, no significant difference in scar scores was found between interventions. At 6 months, histologic analysis suggested decreased inflammatory cell invasion of the dermal stapler-closed scar. Conclusion: Closure using the absorbable dermal stapler can be performed significantly faster than standard suture closure techniques, allowing for a more cost-effective incisional closure with equivalent cosmetic results.

Perioperative Antibiotics in the Setting of Microvascular Free Tissue Transfer: Current Practices

Background:Gustilo IIIB fractures involve high-energy tibial fractures for which there is inadequate soft tissue coverage. In addition to orthopedic fixation, these injuries require soft tissue reconstruction, often in the form of a microvascular free flap. Although the majority of orthopedic literature favorably compares intramedullary rod fixation to external fixation in open tibial fractures, these studies have not focused on the role of either method of fixation in relation to the soft tissue reconstruction. Methods:Because we had noted numerous complications after providing free-flap coverage over intramedullary rodded fractures, we sought to investigate whether there were differences in outcomes between free flap-covered lower-extremity fractures which were fixated by external fixation versus intramedullary rods. A retrospective chart review was performed on all patients in our institution who had lower-extremity free flaps for coverage of Gustilo IIIB fractures from 1995–2005 in relation to the type of bony fixation. Results:Of the 38 patients studied, 18 underwent external fixation of the tibial fracture, and 20 had intramedullary rodding. Overall flap survival was 95%, with 1 failure in each group. However, the intramedullary rod group had higher incidences of wound infection, osteomyelitis, and bony nonunion (25%, 25%, and 40%, respectively) than the external fixation group (6%, 11%, 17%, respectively). Conclusions:For Gustilo IIIB fractures that require free-flap coverage, the added bony and soft tissue manipulation required for intramedullary rodding may disrupt the surrounding blood supply and lead to higher rates of complications that threaten the overall success of the reconstruction. Plastic and orthopedic surgeons should discuss the optimal method of bony fixation for complex tibial fractures when a free flap will likely be needed for soft tissue coverage. This integrated team approach may help minimize complications.

A Recommended Protocol for the Immediate Postoperative Care of Lower Extremity Free-Flap Reconstructions

Microvascular free tissue transfer is a ubiquitous and routine method of restoring anatomic defects. There is a paucity of data regarding the role of perioperative antibiotics in free tissue transfer. We designed a survey to explore usage patterns among microvascular surgeons and thereby define a standard of care. A 24-question survey regarding the perioperative antibiotic use in microvascular head and neck, breast, and lower extremity reconstruction was sent to all those members of the American Society for Reconstructive Microsurgery who had registered e-mail addresses ( N = 450). Ninety-nine members responded. A first-generation cephalosporin is the most frequent choice of perioperative antibiotics across most categories: 93.5% for breast, 59.2% for head and neck, 91.1% for nontraumatic lower extremity, and 84.9% for traumatic noninfected lower extremity reconstruction. In penicillin-allergic patients, clindamycin is the most common choice. For traumatic lower extremity reconstruction in the presence of soft tissue infection or osteomyelitis, culture and sensitivity results determine the selection of perioperative antibiotics in 74%. A first-generation cephalosporin is the standard of care for perioperative antibiotic use in microvascular breast, head and neck, nontraumatic lower extremity, and traumatic noninfected lower extremity reconstruction. No consensus exists regarding the appropriate duration of coverage. These data may serve as a guide until a large controlled prospective trial is performed and a standard of care is established.