Shayan A. Izaddoost

Discs Lost, a Novel Multi-PDZ Domain Protein, Establishes and Maintains Epithelial Polarity

Polarization of epithelial cells depends on a hierarchical process whereby specific membrane-associated proteins become targeted to specialized membrane domains. Here, we describe a novel Drosophila protein, Discs Lost (DLT), that plays a crucial role in the polarization of embryonic epithelia during cellular blastoderm formation. At subsequent stages of development, DLT interacts with the apical determinant Crumbs (CRB) and the laterally localized protein Neurexin IV (NRX IV). Mutations in dlt or double-stranded RNA interference lead to aberrant localization of CRB and NRX IV and cause a concomitant loss of epithelial cell polarity. Hence, DLT is required to establish and maintain cell polarity and participates in different molecular complexes that define apical and lateral membrane domains.

Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres

Drosophila Crumbs (Crb) is required for apical–basal polarity and is an apical determinant in embryonic epithelia. Here, we describe properties of Crb that control the position and integrity of the photoreceptor adherens junction and photosensitive organ, or rhabdomere. In contrast to normal photoreceptor adherens junctions and rhabdomeres, which span the depth of the retina, adherens junctions and rhabdomeres of Crb-deficient photoreceptors initially accumulate at the top of the retina and fail to maintain their integrity as they stretch to the retinal floor. We show that Crb controls localization of the adherens junction through its intracellular domain containing a putative binding site for a protein 4.1 superfamily protein (FERM). Although loss of Crb or overexpression of the FERM binding domain causes mislocalization of adherens junctions, they do not result in a significant loss of photoreceptor polarity. Mutations in CRB1, a human homologue of crb, are associated with photoreceptor degeneration in retinitis pigmentosa 12 (RP12) and Leber congenital amaurosis (LCA). The intracellular domain of CRB1 behaves similarly to its Drosophila counterpart when overexpressed in the fly eye. Our studies may provide clues for mechanisms of photoreceptor degeneration in RP12 and LCA.

Novel signaling from the peripodial membrane is essential for eye disc patterning in Drosophila.

The Drosophila eye disc is a sac of single layer epithelium with two opposing sides, the peripodial membrane (PM) and the disc proper (DP). Retinal morphogenesis is organized by Notch signaling at the dorsoventral (DV) boundary in the DP. Functions of the PM in coordinating growth and patterning of the DP are unknown. We show that the secreted proteins, Hedgehog, Wingless, and Decapentaplegic, are expressed in the PM, yet they control DP expression of Notch ligands, Delta and Serrate. Peripodial clones expressing Hedgehog induce Serrate in the DP while loss of peripodial Hedgehog disrupts disc growth. Furthermore, PM cells extend cellular processes to the DP. Therefore, peripodial signaling is critical for eye pattern formation and may be mediated by peripodial processes.

Salvage of infected left ventricular assist device with antibiotic beads.

Background: The use of left ventricular assist devices has become common for the treatment of end-stage heart failure, both as a bridge to transplantation and as destination therapy. The nature of these devices and the comorbid conditions of the patients in whom the devices are implanted lead to high rates of device infection that are related directly to mortality. Methods: Over 2 years, the senior author (S.A.I.) treated 26 patients with left ventricular assist device infections, ranging from superficial driveline infections to deeper pocket infections and device infections. An algorithm involving the use of repeated débridement and placement of antibiotic beads was used in treatment of these infections. Once cleared of infection, patients were treated with definitive closure or flap coverage of the formerly infected device component. Results: Seventeen of 26 patients with left ventricular assist device–related infections were cleared of their infection using this method. Ten of these patients underwent flap coverage of the device after their infection was cleared. In patients that were cleared of infection, mortality was 29 percent, whereas patients with recalcitrant infections had a mortality of 67 percent over the course of the study. Conclusions: A systematic approach to treating left ventricular assist device–related infections has the potential to treat and clear these infections, with promising overall survival rates. This proposed algorithm led to high infection clearance rates compared with previously published literature. Infection clearance in patients on left ventricular assist device destination therapy may result in mortality rates approaching those of their uninfected peers. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Ultra-thin, Fascia-only Anterolateral Thigh Flap

BACKGROUND While many potential donor sites have been described for fascial (fascia-only) flaps, a fascial flap harvested from the anterolateral thigh (ALT) donor site has not gained popularity, likely because of concerns regarding inadequate perfusion of the deep fascia. However, recent clinical experience demonstrates that the ALT fascia-only flap is a suitable option for reconstructions necessitating thin and pliable coverage. METHODS In this study a retrospective chart review was performed examining the clinical experience of two plastic surgeons with the fascia-only ALT perforator flap from 2008 to 2012. Each flap was initially raised as a standard ALT flap, but all the overlying skin and adipose tissue was excised off the deep fascia before the inset, resulting in the creation of a fascia-only ALT flap. Immediate split- or full-thickness skin grafts were used to cover the flap. The results are reported in this article. RESULTS Overall seven patients underwent reconstruction of wounds using either free (six) or pedicled (one) fascia-only ALT flaps (length, 10-20 cm, width, 5-10 cm). The following regions were successfully reconstructed using a fascia-only ALT flap: occipital scalp, lower extremity, upper extremity, and groin. All patients were followed for at least 6 months postoperatively. CONCLUSIONS The fascia-only ALT flap was successfully used to reconstruct a variety of defects in seven patients. The authors experience demonstrates the viability of the fascia-only version of the ALT flap for reconstructions requiring thin coverage with good contour, and further adds to the versatility of the ALT as a donor site for flaps.

The Delay Phenomenon: A Compilation of Knowledge across Specialties

Objective The purpose of this article is to review and integrate the available literature in different fields to gain a better understanding of the basic physiology and optimize vascular delay as a reconstructive surgery technique. Methods A broad search of the literature was performed using the Medline database. Two queries were performed using “vascular delay,” a search expected to yield perspectives from the field of plastic and reconstructive surgery, and “ischemic preconditioning,” (IPC) which was expected to yield research on the same topic in other fields. Results The combined searches yielded a total of 1824 abstracts. The “vascular delay” query yielded 76 articles from 1984 to 2011. The “ischemic preconditioning” query yielded 6534 articles, ranging from 1980 to 2012. The abstracts were screened for those from other specialties in addition to reconstructive surgery, analyzed potential or current uses of vascular delay in practice, or provided developments in understanding the pathophysiology of vascular delay. 70 articles were identified that met inclusion criteria and were applicable to vascular delay or ischemic preconditioning. Conclusion An understanding of IPCs implementation and mechanisms in other fields has beneficial implications for the field of reconstructive surgery in the context of the delay phenomenon. Despite an incomplete model of IPCs pathways, the anti-oxidative, anti-apoptotic and anti-inflammatory benefits of IPC are well recognized. The activation of angiogenic genes through IPC could allow for complex flap design, even in poorly vascularized regions. IPCs promotion of angiogenesis and reduction of endothelial dysfunction remain most applicable to reconstructive surgery in reducing graft-related complications and flap failure.

Sternal reconstruction with omental and pectoralis flaps: a review of 415 consecutive cases.

BackgroundSternal wound infections are a life-threatening complication of cardiovascular surgery, and management can present a great challenge for the plastic surgeon. Successful treatment involves a multidisciplinary approach, immediate detection, meticulous debridement, and delivery of vascularized tissue to the infected wound bed. MethodsTwenty-nine years experience of a single surgeon in 415 sternal wound reconstructions is retrospectively analyzed. Flap choice was based on the amount of vascularized tissue required. Low-risk, early infections were treated with debridement and a single flap. Large, high-risk wounds were treated with multiple debridements and covered with a combination of flaps to reduce infection and eliminate dead space. ResultsImmediate wound closure with aggressive debridement and flap coverage in a single-stage early in the series (first 12 patients, 1980–1981) led to a mortality rate of 25% due to sepsis and cardiovascular instability. Thereafter, treatment was altered, and patient stability and wound preparation were emphasized, often requiring multiple debridements (91% of all patients). Nine percent of patients, with early low-risk infections, underwent single-stage rewiring and coverage with pectoralis or omental flaps. Coverage of multiple debrided purulent wounds was performed using pectoralis major flap (37% of total number of patients), omentum (18%), a pectoralis/omentum combination (34%), or rectus abdominis flap (2%). A multistage approach and use of 2 flaps for coverage resulted in a 1.5% mortality due to sepsis, 2.5% infection rate, 1.5% skin necrosis rate, and 1.5% hematoma/seroma rate. The use of multiple flaps in large, complex wounds resulted in a complication rate similar to smaller wounds covered with a single flap. In all, 3.5% of the patients required a salvage operation with alternate flaps. ConclusionThis large series demonstrates the importance of early detection of infection, meticulous staged debridement of nonviable tissue, and elimination of dead space with multiple vascularized flaps.

Compartment syndrome in all four extremities: a rare case associated with systemic capillary leak syndrome

While isolated limb injuries often lead to suspicion for and treatment of compartment syndrome, multi-limb compartment syndrome induced by a systemic disease is a rare entity, in which lack of immediate diagnosis can have catastrophic consequences to the patient. We present a patient with idiopathic systemic capillary leak syndrome (SCLS) resulting in compartment syndrome in all four extremities. Treatment required bilateral hand, forearm, calf, and thigh fasciotomies. Presenting symptoms included pain in all four extremities, malaise, and confusion. Laboratory data included polycythemia, hypoalbuminemia, leukocytosis, and elevated creatinine, but not a monoclonal spike on serum electrophoresis as is common in SCLS. Thus, when faced with clinical evidence of multiple extremity compartment syndrome, the surgeon should consider systemic disorders, such as SCLS, and aggressively treat the compartment syndrome as well as the underlying disease.

One-step Salvage of Infected Prosthetic Breast Reconstructions Using Antibiotic-impregnated Polymethylmethacrylate Plates and Concurrent Tissue Expander Exchange

PurposePeriprosthetic infection represents a major complication in breast reconstruction, frequently leading to expander-implant loss. Recent studies report variable success in the salvage of infected breast prostheses through systemic antibiotic therapy and surgical intervention. There is currently no consensus regarding a management algorithm for attempted salvage. The purpose of this pilot study was to evaluate the early outcomes of a protocol using antibiotic-impregnated polymethylmethacrylate (PMMA) implant placement with expander device exchange. MethodsA retrospective database was queried to identify all patients with infected implant-based breast reconstruction who were treated by the study authors and who underwent attempted salvage under the study protocol. All patients received intravenous antibiotics followed by surgical debridement of the infected pocket, insertion of antibiotic-impregnated PMMA plates and/or beads, device exchange, and postoperative antibiotics. After clinical resolution of infection, tissue expansion was performed with the PMMA implants remaining in situ until exchanged to permanent implants. ResultsAll patients with infected prosthetic breast reconstructions achieved implant pocket sterilization using this method. At a mean follow-up of 8.2 months (range, 1–19 months), none of these patients have required reoperation for capsular contracture. One patient, while under treatment with prednisone for a rash, developed recurrent infection, which led to explantation of her implant. Two patients underwent radiation therapy while an antibiotic plate and tissue expander were in place, with no observed exposure or infection recurrence. ConclusionsSustained local antibiotic delivery using PMMA implants and expander device exchange can successfully salvage an infected breast implant. Perceived benefits include shorter time to completed reconstruction, preserved skin envelope integrity, and possibly improved long-term aesthetic outcomes.

Use of a Three-Dimensional Model to Optimize a MEDPOR Implant for Delayed Reconstruction of a Suprastructure Maxillectomy Defect.

The use of a three-dimensional (3-D) model has been well described for craniomaxillofacial reconstruction, especially with the preoperative planning of free fibula flaps. This article reports the application of an innovative 3-D model approach for the calculation of the exact contours, angles, length, and general morphology of a prefabricated MEDPOR 2/3 orbital implant for reconstruction of a suprastructure maxillectomy defect. The 3-D model allowed intraoperative modification of the MEDPOR implant which decreased the risk of iatrogenic harm, contamination while also improving aesthetic results and function. With the aid of preoperative 3-D models, porous polypropylene facial implants can be contoured efficiently intraoperatively to precisely reconstruct complex craniomaxillofacial defects.