Ingrid Ganske

Adenovirus Fiber Disrupts CAR-Mediated Intercellular Adhesion Allowing Virus Escape

Adenovirus binds its receptor (CAR), enters cells, and replicates. It must then escape to the environment to infect a new host. We found that following infection, human airway epithelia first released adenovirus to the basolateral surface. Virus then traveled between epithelial cells to emerge on the apical surface. Adenovirus fiber protein, which is produced during viral replication, facilitated apical escape. Fiber binds CAR, which sits on the basolateral membrane where it maintains tight junction integrity. When fiber bound CAR, it disrupted junctional integrity, allowing virus to filter between the cells and emerge apically. Thus, adenovirus exploits its receptor for two important but distinct steps in its life cycle: entry into host cells and escape across epithelial barriers to the environment.

Minimizing Complications With the Use of Acellular Dermal Matrix for Immediate Implant-based Breast Reconstruction

BackgroundAcellular dermal matrix (ADM) use in implant-based breast reconstruction has been associated with higher rates of postoperative seroma and infection. This follow-up study was performed to determine whether specific modifications in technique are associated with a reduction in the rate of complications. MethodsThe authors performed a retrospective analysis of immediate ADM-assisted implant-based breast reconstructions performed by the lead author (Y.C.) during an 18-month period after instituting specific modifications to prevent seroma. These included draining both the submastectomy and sub-ADM planes, lowering the threshold for drain removal, and addition of postoperative soft compression dressings and surgical bras. A total of 179 implant-based reconstructions were evaluated for rates of complications, including infection, hematoma, seroma, and skin flap necrosis. These were compared to results of a series of 150 similar procedures performed by the lead author before institution of the procedural modifications described. ResultsSeroma rate decreased from 18.6% to 4.7% (P = 0.0022), and major infection rate decreased from 7% to 1.9% (0.0250). ConclusionsAlthough implant-based breast reconstruction using ADM has been associated with increased seroma and possible infection rates, the use of specific clinical practices designed to prevent seroma has minimized our rate of these postoperative complications.

Comparison of clinical outcomes and patient satisfaction in immediate single-stage versus two-stage implant-based breast reconstruction.

Background: The purpose of this study was to assess the outcomes of immediate, single-stage, implant-based reconstruction compared with traditional, two-stage reconstruction (i.e., tissue expander placement followed by exchange to implant). Methods: A retrospective review of consecutive patients who underwent immediate unilateral or bilateral breast reconstruction over an 8-year period was performed. The primary predictor variable was method of reconstruction (single-stage versus two-stage). Outcome measures were postoperative complication rates, revision rates, and BREAST-Q patient satisfaction scores. Descriptive, bivariate, and multiple regression statistics were computed. Results: The study sample consisted of 346 subjects who underwent reconstruction of 582 breasts (166 single-stage and 416 two-stage reconstructions). Complication rates between the single-stage and two-stage groups were similar for minor infections, major infections, hematoma formation, seroma formation, minor necrosis, and major necrosis (p ≥ 0.20). In a multiple logistic regression model, subjects undergoing single-stage reconstruction were found to be 87 percent more likely to require revision necessitating an additional operation (p = 0.005). In an adjusted regression model, subjects undergoing two-stage reconstruction had higher BREAST-Q scores for satisfaction with medical and office staff (p ⩽ 0.02). Subjects undergoing single-stage reconstruction had higher sexual well-being satisfaction scores. Conclusions: There is no significant difference in complication rates between single-stage versus two-stage implant-based breast reconstructions. Although single-stage reconstruction is associated with higher sexual well-being satisfaction, it is more than 80 percent more likely to require additional operative revisions. Two-stage reconstruction is associated with significantly higher satisfaction with the medical and office staff. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Delayed hypersensitivity reaction to acellular dermal matrix in breast reconstruction: the red breast syndrome?

BackgroundAcellular dermal matrix (ADM) has become a valuable tool in reconstructive breast surgery, in part because it has been considered to be a non-reactive and non-immunogenic entity. However, some patients who undergo breast reconstruction with ADMs develop postoperative erythema overlying their ADM grafts. The etiology of this phenomenon is poorly understood. MethodsIn this article, we summarize clinical cases in which patients developed localized breast erythema following reconstruction with ADMs. We review what is known about postoperative breast erythema after ADM-based breast reconstructions and the possible antigenicity of biologic mesh implants. ResultsWe report 4 implant-based breast reconstruction patients who developed erythematous reactions overlying the region where ADM was placed: one demonstrated a delayed-type hypersensitivity reaction on punch biopsy of the affected skin, leading to removal of the biologic product; 2 others had a similar clinical presentation that responded to corticosteroids without removal of the biologic material, with 1 patient experiencing recrudescence of erythema that responded fully to a second course of corticosteroids; and a fourth showed erythema that was only moderately responsive to antibiotic therapy but which improved consistently after the patient initiated chemotherapy. ConclusionWe propose that the etiology of erythema overlying ADM grafts, and the so-called red breast syndrome, may in some patients be a delayed-type hypersensitivity reaction to the ADM product. Affected patients may benefit from treatment with corticosteroids or similar medications, and that such treatment may, in some cases, enable patients to retain the ADM grafts and enable salvage of the reconstructed breast.

Abstract 89: Minimizing Complications Associated With Use of Acellular Dermal Matrix in Implant-Based Breast Reconstruction

Purpose: Acellular dermal matrix (ADM) is a common adjunct to tissue expander (TE) and implant-based breast reconstruction. While ADM can enhance aesthetic outcome, its use has been associated with seroma and infection. Specific procedural modifications have been made to reduce seroma and minimize complications when using ADM, including changes in drain position, drainage duration, and addition of post-operative soft compression. This study was performed to evaluate their effectiveness.

The Changing Nasolabial Dimensions following Repair of Unilateral Cleft Lip: An Anthropometric Study in Late Childhood

Background: Repair of unilateral cleft lip and nasal deformity in three dimensions requires anticipation of changes in the fourth dimension that can be determined by periodic and objective assessment. Methods: Fifty patients with unilateral cleft lip with or without cleft palate underwent primary repair from 1999 to 2004 and were followed through 2014. Anthropometry was performed immediately postoperatively and at a first and second follow-up interval, occurring at an average age of 6.6 and 11.5 years, respectively. Measured differences between cleft and noncleft sides included heminasal width (subnasale-alare), cutaneous labial height (subnasale-crista philtri inferior, subalare-crista philtri inferior), and transverse labial width at the cutaneous-vermilion border (crista philtri inferior-chelion). Contrasts for the rates of growth were assessed with t tests for correlated measures. Using the same method, the difference between growth on cleft and noncleft sides in the second period was compared to that in the first period. Results: Heminasal width remained narrower on the cleft side, but this difference decreased over time. Subnasale-crista philtri inferior remained longer on the cleft side; there was no difference between the rate of growth on the cleft and noncleft sides in the second period. Subalare-crista philtri inferior remained shorter on the cleft side by a consistent difference at both times of follow-up measurements. Transverse labial width at the cutaneous-vermilion border remained shorter on the cleft side, but this difference decreased in the second period. Conclusion: Understanding how nasolabial features change with growth is critical to crafting the initial repair of unilateral cleft lip and nasal deformity. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Cleft Lip and Palate in CHARGE Syndrome: Phenotypic Features That Influence Management

Objective: Infants with syndromic cleft lip and/or cleft palate (CL/P) often require more complex care than their nonsyndromic counterparts. Our purpose was to (1) determine the prevalence of CL/P in patients with CHARGE syndrome and (2) highlight factors that affect management in this subset of children. Design: This is a retrospective review from 1998 to 2016. Patients: Patients with CHARGE syndrome were diagnosed clinically and genetically. Main Outcomes Measures: Prevalence of CL/P was determined and clinical details tabulated: phenotypic anomalies, cleft types, operative treatment, and results of repair. Results: CHARGE syndrome was confirmed in 44 patients: 11 (25%) had cleft lip and palate and 1 had cleft palate only. Surgical treatment followed our usual protocols. Two patients with cardiac anomalies had prolonged recovery following surgical correction, necessitating palatal closure prior to nasolabial repair. One of these patients was too old for dentofacial orthopedics and underwent combined premaxillary setback and palatoplasty, prior to labial closure. Velopharyngeal insufficiency was frequent (n = 3/7). All patients had feeding difficulty and required a gastrostomy tube. All patients had neurosensory hearing loss; anomalies of the semicircular canals were frequent (n = 3/4). External auricular anomalies, colobomas, and cardiovascular anomalies were also common (n = 8/11). Other associated anomalies were choanal atresia (n = 4/11) and tracheoesophageal fistula (n = 2/11). Conclusions: CHARGE syndrome is an under-recognized genetic cause of cleft lip and palate. Hearing loss and speech and feeding difficulties often occur in these infants. Diagnosis can be delayed if the child presents with covert phenotypic features, such as chorioretinal colobomas, semicircular canal hypoplasia, and unilateral choanal atresia.

Abstract: Long-Term Outcomes Following Flap Reconstruction in Pediatric Pressure Ulcers

Long-Term Outcomes Following Flap Reconstruction in Pediatric Pressure Ulcers The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Firriolo, Joseph M., Ingrid M. Ganske, Carolyn M. Pike, Catherine Caillouette, Heather R. Faulkner, and Brian I. Labow. 2017. “Abstract: Long-Term Outcomes Following Flap Reconstruction in Pediatric Pressure Ulcers.” Plastic and Reconstructive Surgery Global Open 5 (9 Suppl): 166-167. doi:10.1097/01.GOX.0000526404.47863.87. http:// dx.doi.org/10.1097/01.GOX.0000526404.47863.87. Published Version doi:10.1097/01.GOX.0000526404.47863.87 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492185 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-ofuse#LAA

Long-term Outcomes After Flap Reconstruction in Pediatric Pressure Ulcers

Background Pressure ulcers refractory to nonoperative management may undergo flap reconstruction. This study aims to evaluate the long-term outcomes and recurrence rates of flap reconstruction for pediatric pressure ulcers. Methods We reviewed the records of patients who underwent flap reconstruction for pressure ulcer(s) from 1995 to 2013. Results Twenty-four patients with 30 pressure ulcers, requiring 52 flaps were included. Ulcers were stages III and IV and mostly involved either the ischia (15/30) or sacrum (8/30). Flaps were followed for a median of 4.9 years. Twenty-three patients were wheelchair dependent, and 20 had sensory impairment at their ulcer site(s). Ten patients had a history of noncompliance with preoperative management, 8 of whom experienced ulcer recurrence. Twenty-one ulcers had underlying osteomyelitis, associated with increased admissions (P = 0.019) and cumulative length of stay (P = 0.031). Overall, there was a 42% recurrence rate in ulceration after flap reconstruction. Recurrence was associated with a preoperative history of noncompliance with nonoperative therapy (P = 0.030), but not with flap type or location, age, sex, body mass index, osteomyelitis, or urinary/fecal incontinence (P > 0.05, all). Conclusions Flap reconstruction can be beneficial in the management of pediatric pressure ulcers. Although high rates of long-term success with this intervention have been reported in children, we found rates of ulcer recurrence similar to that seen in adults. Poor compliance with nonoperative care and failure to modify the biopsychosocial perpetuators of pressure ulcers will likely eventuate in postoperative recurrence. Despite the many comorbidities observed in our patient sample, compliance was the best indicator of long-term skin integrity and flap success.

A Different Angle: Physician and Architect

There is increasing need for medical expertise within architecture, especially looking at the relationship between design and health outcomes, increasing financial constraints, and technological advances. Design considerations in healthcare include operational efficiency, patient safety, environmental issues, disaster planning, pandemic preparedness, and physiologic experience. Architectural education can be informal or require a formal degree, depending on your role and degree of involvement with design.