One-Stage Deep Inferior Epigastric Perforator Flap Salvage of Infected Tissue Expanders.

BACKGROUND: Tissue expander-based breast reconstruction is associated with high rates of infectious complications, often leading to tissue expander explants and delays in receipt of definitive breast reconstruction and adjuvant therapy. In this study, we describe a single-stage technique where deep inferior epigastric artery perforator (DIEP) flaps are used to salvage actively infected tissue expanders among patients originally planning for free flap reconstruction. METHODS: In this technique, patients with tissue expander infections without systemic illness are maintained on oral antibiotics until the day of their DIEP flap surgery, at which time tissue expander explant is performed in conjunction with aggressive attempt at total capsulectomy and immediate DIEP flap reconstruction. Patients are maintained on 1-2 weeks of oral antibiotics tailored to culture data. Patients undergoing this immediate salvage protocol were retrospectively reviewed, and complications and length of stay were assessed. RESULTS: In a retrospective series, a total of six consecutive patients with culture-proven tissue expander infections underwent tissue expander removal and DIEP flap reconstruction in a single stage and were maintained on 7-14 days of oral antibiotics postoperatively. Within this cohort, no surgical site infections, microvascular complications, partial flap losses, reoperations, or returns to the operating room were noted within a 90-day period. CONCLUSIONS: Among a select cohort of patients, actively infected tissue expanders may be salvaged with free flap breast reconstruction in a single surgery with a low incidence of postoperative complications. Prospective studies are needed to evaluate the influence of this treatment strategy on costs, number of surgeries, and dissatisfaction after staged breast reconstruction complicated by tissue expander infections.

A Multi-institutional Analysis of a Textbook Outcome Among Patients Undergoing Microvascular Breast Reconstruction.

BACKGROUND: Individual outcomes may not accurately reflect the quality of perioperative care. Textbook outcomes (TOs) are composite metrics that provide a comprehensive evaluation of hospital performance and surgical quality. This study aimed to investigate the prevalence and predictors of TOs in a multi-institutional cohort of patients who underwent breast reconstruction with deep inferior epigastric artery perforator flaps. METHODS: For autologous reconstruction, a TO was previously defined as a procedure without intraoperative complications, reoperation, infection requiring intravenous antibiotics, readmission, mortality, systemic complications, operative duration ≤12 hours for bilateral and ≤10 hours for unilateral/stacked reconstruction, and length of stay (LOS) ≤5 days. We investigated associations between patient-level factors and achieving a TO using multivariable regression analysis. RESULTS: Of 1000 patients, most (73.2%) met a TO. The most common reasons for deviation from a TO were reoperation (9.6%), prolonged operative time (9.5%), and prolonged LOS (9.2%). On univariate analysis, tobacco use, obesity, widowed/divorced marital status, and contralateral prophylactic mastectomy or bilateral reconstruction were associated with a lower likelihood of TOs (P < 0.05). After adjustment, bilateral prophylactic mastectomy (odds ratio [OR], 5.71; P = 0.029) and hormonal therapy (OR, 1.53; P = 0.050) were associated with a higher likelihood of TOs; higher body mass index (OR, 0.91; P = <0.001) was associated with a lower likelihood. CONCLUSION: Approximately 30% of patients did not achieve a TO, and the likelihood of achieving a TO was influenced by patient and procedural factors. Future studies should investigate how this metric may be used to evaluate patient and hospital-level performance to improve the quality of care in reconstructive surgery.

Textbook outcomes in DIEP flap breast reconstruction: a Delphi study to establish consensus.

PURPOSE: Composite measures, like textbook outcomes, may be superior to individual metrics when assessing hospital performance and quality of care. This study utilized a Delphi process to define a textbook outcome in DIEP flap breast reconstruction. METHODS: A two-round Delphi survey defined: (1) A textbook outcome, (2) Exclusion criteria for a study population, and (3) Respondent opinion regarding textbook outcomes. An a priori threshold of ≥ 70% agreement among respondents established consensus among the tested statements. RESULTS: Out of 85 invitees, 48 responded in the first round and 41 in the second. A textbook outcome was defined as one that meets the following within 90 days: (1) No intraoperative complications, (2) Operative duration ≤ 12 h for bilateral and ≤ 10 h for unilateral/stacked reconstruction, (3) No post-surgical complications requiring re-operation, (4) No surgical site infection requiring IV antibiotics, (5) No readmission, (6) No mortality, (7) No systemic complications, and (8) Length of stay < 5 days. Exclusion criteria for medical and surgical characteristics (e.g., BMI > 40, HgbA1c > 7) and case-volume cut-offs for providers (≥ 21) and institutions (≥ 44) were defined. Most agreed that textbook outcomes should be defined for complex plastic surgery procedures (75%) and utilized to gauge hospital performance for microsurgical breast reconstruction (77%). CONCLUSION: This Delphi study identified (1) Key elements of a textbook outcome for DIEP flap breast reconstruction, (2) Exclusion criteria for future studies, and (3) Characterized surgeon opinions regarding the utility of textbook outcomes in serving as quality metric for breast reconstruction care.

Air or Saline? A Propensity Score-Matched Analysis on the Effect of Tissue Expander Fill on Complications in Immediate Breast Reconstruction.

BACKGROUND: Tissue expander fill medium and volume have implications for the pressure exerted on mastectomy skin flaps. This study evaluated the influence of initial fill medium (air vs. saline) on complications in immediate breast reconstruction within a propensity score-matched cohort. PATIENTS AND METHODS: Patients undergoing immediate tissue expander-based breast reconstruction with initial intraoperative fill with air were propensity score matched 1:2 to those with saline initial fill based on patient and tissue expander characteristics. Incidence of overall and ischemic complications were compared by fill medium (air vs. saline). RESULTS: A total of 584 patients were included, including 130 (22.2%) with initial fill with air, 377 (64.6%) with initial fill with saline, and 77 (13.2%) with 0 cc of initial fill. After multivariate adjustment, higher intraoperative fill volume was associated with increased risk of mastectomy skin flap necrosis [regression coefficient (RC) 15.7; p = 0.049]. Propensity score matching was then conducted among 360 patients (Air: 120 patients vs. Saline: 240 patients). After propensity score matching, there were no significant differences in the incidences of mastectomy skin flap necrosis, extrusion, reoperation, or readmission between the air and saline cohorts (all p > 0.05). However, initial fill with air was associated with lower incidence of infection requiring oral antibiotics (p = 0.003), seroma (p = 0.004), and nipple necrosis (p = 0.03). CONCLUSIONS: Within a propensity score-matched cohort, initial fill with air was associated with a lower incidence of complications, including ischemic complications after nipple-sparing mastectomy. Initial fill with air and lower fill volumes may be strategies to reducing risk of ischemic complications among high-risk patients.

Efficacy of Prophylactic Postoperative Antibiotics in Tissue Expander-Based Breast Reconstruction: A Propensity Score-Matched Analysis.

BACKGROUND: Conflicting evidence exists regarding the utility of prophylactic postoperative antibiotics in tissue expander (TE)-based breast reconstruction. This study evaluated the risk of surgical-site infection between patients receiving 24 hours of perioperative antibiotics alone versus prolonged postoperative antibiotics within a propensity score-matched cohort. METHODS: Patients undergoing TE-based breast reconstruction receiving 24 hours of perioperative antibiotics alone were propensity score-matched 1:3 to patients receiving postoperative antibiotics based on demographics, comorbidities, and treatment factors. Incidence of surgical-site infection was compared based on duration of antibiotic prophylaxis. RESULTS: Of a total of 431 patients undergoing TE-based breast reconstruction, postoperative antibiotics were prescribed in 77.2%. Within this cohort, 348 were included for propensity matching (no antibiotics, 87 patients; antibiotics, 261 patients). After propensity score matching, there was no significant difference in incidence of infection requiring intravenous (no antibiotics, 6.9%; antibiotics, 4.6%; P = 0.35) or oral antibiotics (no antibiotics, 11.5%; antibiotics, 16.1%; P = 0.16). In addition, rates of unplanned reoperation ( P = 0.88) and 30-day readmission ( P = 0.19) were similar. After multivariate adjustment, prescription of postoperative antibiotics was not associated with a reduction in surgical-site infection (OR, 0.5; 95% CI, -0.3 to 1.3; P = 0.23). CONCLUSIONS: Within a propensity score-matched cohort accounting for patient comorbidities and receipt of adjuvant therapies, prescription of postoperative antibiotics after TE-based breast reconstruction conferred no improvement in rates of TE infection, reoperation, or unplanned health care use. These data underscore the need for multicenter randomized trials on the utility of antibiotic prophylaxis in TE-based breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Vascularized composite tissue allotransplantation--state of the art.

Vascularized composite tissue allotransplantation is a viable treatment option for injuries and defects that involve multiple layers of functional tissue. In the past 15 yr, more than 150 vascularized composite allotransplantation (VCA) surgeries have been reported for various anatomic locations including - but not limited to - trachea, larynx, abdominal wall, face, and upper and lower extremities. VCA can achieve a level of esthetic and functional restoration that is currently unattainable using conventional reconstructive techniques. Although the risks of lifelong immunosuppression continue to be an important factor when evaluating the benefits of VCA, reported short- and long-term outcomes have been excellent, thus far. Acute rejections are common in the early post-operative period, and immunosuppression-related side effects have been manageable. A multidisciplinary approach to the management of VCA has proven successful. Reports of long-term graft losses have been rare, while several factors may play a role in the pathophysiology of chronic graft deterioration in VCA. Alternative approaches to immunosuppression such as cellular therapies and immunomodulation hold promise, although their role is so far not defined. Experimental protocols for VCA are currently being explored. Moving forward, it will be exciting to see whether VCA-specific aspects of allorecognition and immune responses will be able to help facilitate tolerance induction.

Vascularized composite allotransplantation and tissue engineering.

For many living with the devastating aftermath of disfiguring facial injuries, extremity amputations, and other composite tissues defects, conventional reconstruction offers limited relief. Full restoration of the face or extremities with anatomic equivalents recently became possible with decades of advancements in transplantation and regenerative medicine. Vascularized composite allotransplantation (VCA) is the transfer of anatomic equivalents from immunologically and aesthetically compatible donors to recipients with severe defects. The transplanted tissues are "composite" because they include multiple types essential for function, for example, skin, muscle, nerves, and blood vessels. More than 100 patients worldwide have benefited from VCA, the majority receiving hand or face transplants. Despite its demonstrated results, the clinical practice of VCA is limited by center experience, public awareness, donor shortage, and the risks of lifelong immune suppression. Tissue engineering (TE) is the generation of customized tissues in the laboratory using cells, biomaterials and bioreactors. Tissue engineering may eventually supersede VCA in the clinic, because it bypasses donor shortage and immune suppression challenges. Billions of dollars have been invested in TE research and development, which are expected to result in a myriad of clinical products within the mid- to long-term. First, tissue engineers must address challenges such as vascularization of engineered tissues and maintenance of phenotype in culture. If these hurdles can be overcome, it is to be hoped that the lessons learned through decades of research in both VCA and TE will act synergistically to generate off-the-shelf composite tissues that can thrive after implantation and in the absence of immune suppression.

Microvascular Breast Reconstruction in the Era of Value-Based Care: Use of a Cosurgeon Is Associated with Reduced Costs, Improved Outcomes, and Added Value.

BACKGROUND: Reducing complications while controlling costs is a central tenet of value-based health care. Bilateral microvascular breast reconstruction is a long operation with a relatively high complication rate. Using a two-surgeon team has been shown to improve safety in bilateral microvascular breast reconstruction; however, its impact on cost and efficiency has not been robustly studied. The authors hypothesized that a cosurgeon for bilateral microvascular breast reconstruction is safe, effective, and associated with reduced costs. METHODS: The authors retrospectively reviewed all patients who underwent bilateral microvascular breast reconstruction with either a single surgeon or surgeon/cosurgeon team over an 18-month period. Charges were converted to costs using the authors' institutional cost-to-charge ratio. Surgeon opportunity costs were estimated using time-driven activity-based costing. Propensity scoring controlled for baseline characteristics between the two groups. A locally weighted logistic regression model analyzed the cosurgeon's impact on outcomes and costs. RESULTS: The authors included 150 bilateral microvascular breast reconstructions (60 single-surgeon and 90 surgeon/cosurgeon reconstructions) with a median follow-up of 15 months. After matching, the presence of a cosurgeon was associated with a significantly reduced mean operative duration (change in operative duration, -107 minutes; p < 0.001) and cost (change in total cost, -$1101.50; p < 0.001), which was even more pronounced when surgeon/cosurgeon teams worked together frequently (change in operative duration, -132 minutes; change in total cost, -$1389; p = 0.007). The weighted logistic regression models identified that a cosurgeon was protective against breast-site complications and trended toward reduced overall and major complication rates. CONCLUSION: The practice of using a of cosurgeon appears to be associated with reduced costs and improved outcomes, thereby potentially adding value to bilateral microvascular breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Defining the Value of Breast Reconstruction Surgeons: Quantifying Clinical Encounter and Operative Volume at an Academic Center.

Despite growing rates of postmastectomy breast reconstruction, the time contribution of breast reconstruction surgeons in comprehensive breast cancer care is often poorly accounted for by hospital and healthcare systems. This study models encounter volume and operative time utilization of breast reconstruction surgeons among patients undergoing postmastectomy breast reconstruction. Methods: All clinical encounters and operative time from a consecutive sample of breast cancer patients undergoing mastectomy and reconstruction were analyzed. Encounter volume and operative time utilization less than or equal to 4 years after diagnosis were modeled over time. Results: A total of 5057 breast cancer encounters were analyzed. Mean (SD) clinical encounter volume was 45.9 (28.5) encounters per patient, with encounter volume varying by specialty [plastic surgery: 16.5; medical oncology: 15.9; breast surgery: 7.2; radiation oncology: 6.3 mean encounters]. Receipt of adjuvant radiation, neoadjuvant chemotherapy, and major complications during reconstruction predicted higher encounter volume. Mean (SD) operative time utilization was 702 (317) minutes per patient [plastic surgery: 547 (305); breast surgery: 155 (71) minutes]. While both encounter volume and operative time for radiation oncologists and breast surgeons, respectively, were concentrated in the first year after diagnosis, medical oncologists and plastic surgeons sustained high clinical and operative time utilization 3 years after breast cancer diagnosis. Conclusions: Encounter volume and operative time utilization with breast reconstruction surgeons persist 3 years after a breast cancer diagnosis and are tied to treatment characteristics and incidence of reconstruction complications. Institutional- and system-level resource allocation must account for the complex and lengthy duration of care inherent to breast reconstruction care.

Rehabilitation of distal radioulnar joint instability.

Distal radioulnar joint (DRUJ) instabilities are common and often combined with other injuries of the interosseous membrane and/or the proximal radioulnar joint. Once they are diagnosed and the treatment is chosen, physiotherapists have limited choices due to the lack of validated protocols. The benefits of proprioception and neuromuscular rehabilitation have been brought to light for the shoulder, knee and ankle joints, among others. However, no program has been described for the DRUJ. The purpose of this article is to study the muscular elements responsible for active DRUJ stability, and to propose a proprioceptive rehabilitation program suited to this condition.

The phosphoinositide pathway of lymphoid cells: labeling after permeabilization by alveolysin, a bacterial sulfhydryl-activated cytolysin.

An improved method allowing incorporation of [3H]myo-inositol into the phosphoinositide pool of human lymphoid cells is described. The procedure devised involves cell permeabilization with a thiol-activated membranolytic toxin, alveolysin, and optimization of the phosphoinositide labeling and extraction. In these conditions 4 to 10% of the added [3H]myo-inositol is found intracellularly and half of this amount (2-5%) is incorporated into the phosphoinositide pool in only 1 h as compared to the classical 0.2 to 0.3% incorporation obtained after 10 to 20 h. The integrity of coupling between receptors and phospholipase C was assessed by the inositol phosphate production after cell stimulation by various agonists.

Diapause in the pea aphid (Acyrthosiphon pisum) is a slowing but not a cessation of development.

BACKGROUND: Many insects undergo a period of arrested development, called diapause, to avoid seasonally recurring adverse conditions. Whilst the phenology and endocrinology of insect diapause have been well studied, there has been comparatively little research into the developmental details of diapause. We investigated developmental aspects of diapause in sexually-produced embryos of the pea aphid, Acyrthosiphon pisum. RESULTS: We found that early stages of embryogenesis progressed at a temperature-independent rate, characteristic of diapause, whereas later stages of embryogenesis progressed at a temperature-dependent rate. However, embryos maintained at very high temperatures during the temperature-independent stage showed severe developmental abnormalities. Under no temperature regime did embryos display a distinct resting stage. Rather, morphological development progressed slowly but continuously throughout embryogenesis. CONCLUSION: Diapause in the pea aphid, and perhaps in many other insects, is a temperature-independent slowing but not a cessation of morphological development. This suggests that the mechanisms limiting developmental rate during diapause may be the same as those controlling developmental rate at other stages of growth.

[Purification of an extracellular thiol-dependent hemolysin from Bacillus alvei]. / Purification de l'hémolysine thiol-dépendante extracellulaire de Bacillus alvei.

Alveolysin a sulfhydryl-dependent cytolytic extracellular protein released by Bacillus alvei has been purified by salting-out by ammonium sulfate, gel filtration, isoelectric focusing on pH gradient and chromatography on DEAE-cellulose. The purified protein after reduction by thiols (active hemolytic form) proved homogeneous by disc polyacrylamide gel electrophoresis and by gel immunodiffusion. The molecular weight was 60,000 daltons, Two molecular forms of pI 5.1 and 7.0 were detected by gel isoelectrofocusing. The toxin was lethal to the mouse. Lytic activity was inhibited by cholesterol and antistreptolysin O anstisera. Immunological cross-reaction was observed between alveolysin and streptolysin O.

The sulphydryl-activated cytolysin and a sphingomyelinase C are the major membrane-damaging factors involved in cooperative (CAMP-like) haemolysis of Listeria spp.

The negative mutant approach was used in this study to identify listerial cytolytic factors involved in cooperative haemolysis (CAMP-like phenomenon) with Staphylococcus aureus and Rhodococcus equi. A Listeria monocytogenes non-haemolytic mutant specifically impaired in listeriolysin O (LLO) production gave no CAMP reaction with S. aureus, and was virtually CAMP-negative with R. equi, indicating that the listerial sulphydryl-activated toxin played a major role in cooperative haemolysis. This was confirmed by direct evidence using purified LLO and alveolysin (from Bacillus alvei) in diffusion CAMP assays. To our knowledge, this is the first evidence of involvement of a sulphydryl-activated toxin in cooperative lytic processes. Phosphatidylcholine- and phosphatidylinositol-specific phospholipases C from L. monocytogenes did not seem to significantly contribute to cooperative haemolysis, as the corresponding mutants displayed wild-type CAMP reactions. In contrast, the sphingomyelinase C from Listeria iva-novii was the cytolytic factor responsible for the characteristic shovel-shaped CAMP reaction shown by this listerial species with R. equi. Possible mechanisms of lytic cooperation are discussed.

Formulations of single or multiple H. pylori antigens with DC Chol adjuvant induce protection by the systemic route in mice. Optimal prophylactic combinations are different from therapeutic ones.

The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol. This compound acts both as a formulating agent and as an adjuvant and induces a balanced Th1/Th2 response shown to be more effective for protection in our previous studies. Urease-DC Chol induced a significant protection in prophylaxis but not in therapeutic immunization. The protection level was between 1.5 and 2 log reduction of bacterial density measured by quantitative culture compared to unimmunized-infected mice. In parallel, the protective efficacy of other H. pylori antigens formulated in a similar way and administered with DC Chol was tested. These antigens were tested alone or in combination in prophylactic and therapeutic regimens. Some combinations of antigens induced a better prophylactic or therapeutic activity than urease alone (0.5-1.5 log further reduction in prophylaxis and therapy respectively, P<0.05). The combinations that induced the best protection were different in prophylaxis and therapy. In conclusion, DC Chol provides a convenient and efficient method to formulate different antigens even when they are present in non-compatible buffers initially. Moreover, the results obtained in protection against H. pylori with such formulations should lead the way to future clinical trials.

Purified -SH-activated toxins (streptolysin O, alveolysin): new tools for determination of platelet enzyme activities.

The purpose of this study was to examine the lytic effect on human platelet preparations (washed, gel-filtered and dextran-isolated) of two sulfhydryl-activated bacterial protein toxins, streptolysin 0 and and alveolysin, and to compare their efficacy with that of other disruptive procedures (freezing and thawing, ultrasonic, mechanical, or nystatin-toluene treatment) as a method for the determination of various platelet enzyme activities. The enzymes assayed were alkaline and acid phosphatases, monoamine oxidase, phenolsulfotransferase, N-acetyltransferase, hydroxyindole-O-methyltransferase, glutathione peroxidase and lactate dehydrogenase. In all cases, the lowest activities were found after freezing and thawing and/or ultrasonic disruption. The highest activities were always observed in the platelet lysates obtained after toxin, and in some instances after nystatin-toluene treatment. Intermediate values were obtained for mechanical disruption. The -SH-activated cytolysins thus appear to be appropriate and gentle tools for the assay of platelet enzymes when compared to the physical or chemical procedures generally employed.

Two different modes of membrane damaging action by bacterial thiol-activated haemolysins.

The mode of action to cause membrane damage to human diploid fibroblasts by streptolysin 0 is not typical for that of all thiol-activated cytolysins. Theta-toxin and alveolysin, on the other hand, share all properties investigated and may thus, with regard to mechanisms of membrane damaging action, constitute a subgroup among thiol-activated haemolysins.

Current principles of facial allotransplantation: the Brigham and Women's Hospital Experience.

BACKGROUND: Facial allotransplantation is a revolutionary operation that has at last introduced the possibility of nearly normal facial restoration to patients afflicted by the most severe cases of facial disfigurement. METHODS: The facial transplantation team at Brigham and Women's Hospital evaluated more than 20 patients as potential face transplant recipients; of these, six became face transplant candidates and underwent full screening procedures. The team performed facial allotransplantations in four of these patients between April of 2009 and May of 2011. This is the largest clinical volume of facial transplant recipients in the United States to date. RESULTS: The authors have learned important lessons from each of these four unique cases and from the more than 20 patients that they have evaluated as potential face transplant recipients. The authors have translated lessons learned through direct experience into a set of fundamental surgical principles of the operation. CONCLUSIONS: The authors' surgical principles emphasize safety, technical feasibility, preservation of functional facial units, and return of motor and sensory function. This article describes each of these principles along with their rationale and, in some instances, illustrates their application.