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Haploinsufficiency of SF3B2 causes craniofacial microsomia [Meeting Abstract]

Timberlake, A; Griffin, C; Heike, C; Hing, A; Cunningham, M; Chitayat, D; Davis, M; Doust, S; Drake, A; Roque, M D; Goldblatt, J; Gustafson, J; Hurtado-Villa, P; Johns, A; Karp, N; Laing, N; Magee, L; Mullegama, S; Pachajoa, H; Hurtado, G L P; Schnur, R; Slee, J; Singer, S; Staffenberg, D; Timms, A; Wise, C; Ignacio, Z; Saint-Jeannet, J -P; Luquetti, D
Background/Purpose: Craniofacial microsomia (CFM) is the second most common congenital facial anomaly, yet its genetic etiology remains unknown. Methods/Description: We perform whole-exome or genome sequencing of 146 kindreds with sporadic (n=138) or familial (n=8) CFM.
Result(s): We identify a highly significant burden of loss of function variants in SF3B2 (P=3.8 x 10-10), a component of the U2 small nuclear ribonucleoprotein complex, in probands. We describe twenty individuals from seven kindreds harboring de novo or transmitted haploinsufficient variants in SF3B2. Probands display mandibular hypoplasia, microtia, facial and preauricular tags, epibulbar dermoids, lateral oral clefts in addition to skeletal and cardiac abnormalities. Targeted morpholino knockdown of SF3B2 in Xenopus results in disruption of cranial neural crest precursor formation and subsequent craniofacial cartilage defects, supporting a link between spliceosome mutations and impaired neural crest development in congenital craniofacial disease.
Conclusion(s): The results establish haploinsufficient variants in SF3B2 as the most prevalent genetic cause of CFM, explaining ~3% of sporadic and ~25% of familial cases
EMBASE:638055114
ISSN: 1545-1569
CID: 5251832

Comparing Incision Choices in Immediate Microvascular Breast Reconstruction after Nipple-Sparing Mastectomy: Unique Considerations to Optimize Outcomes

Salibian, Ara A; Bekisz, Jonathan M; Frey, Jordan D; Thanik, Vishal D; Levine, Jamie P; Karp, Nolan S; Choi, Mihye
BACKGROUND:Incision planning is a critical factor in nipple-sparing mastectomy outcomes. Evidence on optimal incision patterns in patients undergoing nipple-sparing mastectomy and immediate microvascular breast reconstruction is lacking in the literature. METHODS:A single-institution retrospective review was performed of consecutive patients undergoing nipple-sparing mastectomy and immediate microvascular autologous reconstruction from 2007 to 2019. Outcomes-including major mastectomy flap necrosis, full nipple-areola complex necrosis, and any major ischemic complication of the skin envelope-were compared among incision types. Multivariable logistic regression identified factors associated with major ischemic complication. RESULTS:Two hundred seventy-nine reconstructions (163 patients) were identified, primarily using internal mammary recipient vessels (98.9 percent). Vertical incisions were used in 139 cases; inframammary, in 53; lateral radial, in 51; and inverted-T, in 35. Thirty-two cases (11.5 percent) had major mastectomy flap necrosis, 11 (3.9 percent) had full nipple-areola complex necrosis, and 38 (13.6 percent) had any major ischemic complication. Inframammary incisions had higher rates of major ischemic complication (25 percent) than vertical (5.8 percent; p < 0.001) and lateral radial (7.8 percent; p = 0.032) incisions. Inverted-T incisions also had higher rates of major ischemic complication (36.1 percent) than both vertical (p < 0.001) and lateral radial (p = 0.002) incisions. Inframammary incisions (OR, 4.382; p = 0.002), inverted-T incisions (OR, 3.952; p = 0.011), and mastectomy weight (OR, 1.003; p < 0.001) were independently associated with an increased risk of major ischemic complication. Inframammary incisions with major ischemic complication demonstrated significantly higher body mass index, mastectomy weight, and flap weight compared to those without. CONCLUSIONS:Inframammary and inverted-T incisions are associated with a higher risk of major ischemic skin envelope complications after nipple-sparing mastectomy and immediate microvascular breast reconstruction. Radial incisions can be considered to optimize recipient vessel exposure without compromising perfusion. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, III.
PMID: 34644280
ISSN: 1529-4242
CID: 5116122

A Systematic Review and Meta-Analysis of Microvascular Stacked and Conjoined-Flap Breast Reconstruction

Salibian, Ara A; Nolan, Ian T; Bekisz, Jonathan M; Frey, Jordan D; Karp, Nolan S; Choi, Mihye; Levine, Jamie P; Thanik, Vishal D
BACKGROUND: Stacked and conjoined (SC) flaps are a useful means of increasing flap volume in autologous breast reconstruction. The majority of studies, however, have been limited to smaller, single-center series. METHODS: A systematic literature review was performed to identify outcomes-based studies on microvascular SC-flap breast reconstruction. Pooled rates of flap and operative characteristics were analyzed. Meta-analytic effect size estimates were calculated for reconstructive complication rates and outcomes of studies comparing SC flaps to non-SC flaps. Meta-regression analysis identified risk factors for flap complications. RESULTS: = 0.00%), though rates of any flap and donor-site complication were similar. Age, body mass index, flap weight, and flap donor site and recipient vessels were not associated with increased risk of any flap complication. CONCLUSION/CONCLUSIONS: A global appraisal of the current evidence demonstrated the safety of SC-flap breast reconstruction with low complication rates, regardless of donor site, and lower rates of fat necrosis compared with non-SC flaps.
PMID: 33592635
ISSN: 1098-8947
CID: 4836342

Acellular Dermal Matrix-Associated Complications in Implant-Based Breast Reconstruction: A Multicenter, Prospective, Randomized Controlled Clinical Trial Comparing Two Human Tissues

Broyles, Justin M; Liao, Eric C; Kim, John; Heistein, Jonathan; Sisco, Mark; Karp, Nolan; Lau, Frank H; Chun, Yoon S
BACKGROUND:Implant-based breast reconstruction accounts for the vast majority of breast reconstruction procedures and is commonly performed with human acellular dermal matrix. There is no consensus as to the optimal human acellular dermal matrix preparation, and high-quality evidence concerning comparative effectiveness is lacking. This study is the first prospective, multicenter, randomized controlled clinical trial to compare human acellular dermal matrix-related complications of the two most commonly used human acellular dermal matrices in implant-based breast reconstruction. The authors hypothesize that there will be no difference in infection, seroma, and reconstructive failure between FlexHD Pliable and AlloDerm RTU. METHODS:The authors conducted a Level 1 prospective, randomized, controlled, multicenter clinical trial to assess complications associated with the use of two human acellular dermal matrices in immediate postmastectomy implant-based breast reconstruction across seven clinical sites. Group A patients received FlexHD Pliable (113 patients with 187 breast reconstructions), and group B patients received AlloDerm RTU (117 patients with 197 breast reconstructions). RESULTS:There was no significant difference with respect to patient demographics, indications, comorbidities, and reconstruction approach between groups. Mean follow-up time was 10.7 ± 3.2 months. There was no statistical difference in the overall matrix-related complications between groups A and B (4.3 percent versus 7.1 percent, p = 0.233). Obesity (OR, 1.14; 95 percent CI, 1.05 to 1.24; p = 0.001) and prepectoral placement of matrix (OR, 4.53; 95 percent CI, 1.82 to 11.3; p = 0.001) were independently associated with greater risks of overall matrix-related complications. CONCLUSION/CONCLUSIONS:This work supports the use of human acellular dermal matrices in implant-based breast reconstruction and demonstrates no significant difference in matrix-related complication rates between FlexHD Pliable and AlloDerm RTU.
PMID: 33877063
ISSN: 1529-4242
CID: 4889092

Breast Reconstruction during the COVID-19 Pandemic: A Systematic Review

Hemal, Kshipra; Boyd, Carter J; Bekisz, Jonathan M; Salibian, Ara A; Choi, Mihye; Karp, Nolan S
Introduction/UNASSIGNED:The COVID-19 pandemic posed unique challenges for breast reconstruction. Many professional organizations initially placed restrictions on breast reconstruction, leading surgeons to conceive innovative protocols for offering breast reconstruction. This study reviewed the current evidence on breast reconstruction during the COVID-19 pandemic to provide guidance for surgeons facing future crises. Methods/UNASSIGNED:The MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews were searched for studies (1) describing implant and autologous breast reconstruction following mastectomy and (2) occurring during or pertaining to the COVID-19 pandemic. Results/UNASSIGNED:Of the 1347 studies identified, 26 were included. Studies discussed type of reconstruction (18, 69%), complications (11, 42%), timing of reconstruction (10, 38%), protocols (10, 38%), COVID-19 screening (7, 27%), and length of hospital stay (7, 27%). The type of reconstruction varied depending on the stage of the pandemic: early on, autologous breast reconstruction was halted to preserve resources, but was later resumed. Within implant-based reconstruction, direct-to-implant was favored over serial tissue expansion. Several protocols were developed, with many emphasizing multidisciplinary collaborations for patient selection, use of specialized measures to reduce risk of COVID-19 transmission, and optimization of same-day discharge. Complication rates following breast reconstruction were similar to pre-pandemic rates. Conclusions/UNASSIGNED:The COVID-19 pandemic has forever changed the landscape of breast reconstruction by raising important questions about delivery of care, cost, and resource utilization. The findings of this review may inform surgeons as they plan for similar future crises or strive for improved patient care and efficacy even during nonpandemic times.
PMCID:8460228
PMID: 34584831
ISSN: 2169-7574
CID: 5067452

Do We Need Support in Prepectoral Breast Reconstruction? Comparing Outcomes with and without ADM

Salibian, Ara A; Bekisz, Jonathan M; Kussie, Hudson C; Thanik, Vishal D; Levine, Jamie P; Choi, Mihye; Karp, Nolan S
Background/UNASSIGNED:The majority of two-stage prepectoral breast reconstruction has been described utilizing acellular dermal matrix (ADM). Although reports of prepectoral breast reconstruction without ADM exist, there is a paucity of comparative studies. Methods/UNASSIGNED:A single-institution retrospective review was performed of consecutive patients undergoing immediate prepectoral two-stage breast reconstruction with tissue expanders from 2017 to 2019. Short-term reconstructive and aesthetic complications were compared between cases that utilized ADM for support and those that did not. Results/UNASSIGNED:0.362). Conclusions/UNASSIGNED:Immediate two-stage prepectoral breast reconstruction with tissue expanders has comparable rates of short-term complications with or without ADM support. Safety of prepectoral expander placement without ADM may warrant more selective ADM use in these cases.
PMCID:8354628
PMID: 34386310
ISSN: 2169-7574
CID: 5066802

Splitting the Difference: Using Synthetic and Biologic Mesh to Decrease Cost in Prepectoral Immediate Implant Breast Reconstruction

Karp, Nolan S; Salibian, Ara A
SUMMARY/CONCLUSIONS:Prepectoral breast reconstruction has minimized morbidity and dynamic deformities associated with submuscular implant-based breast reconstruction. However, reliance on implant coverage with acellular dermal matrix in immediate implant reconstruction remains limited by high material costs. The authors describe a technique in which anterior implant coverage in prepectoral reconstruction is split into acellular dermal matrix inferolaterally and synthetic, absorbable mesh superiorly. Use of acellular dermal matrix inferiorly provides coverage and reinforces the inframammary fold, whereas the absorbable mesh is trimmed and sutured to the acellular dermal matrix at the appropriate tension to support the implant and relieve pressure on mastectomy flaps. A retrospective review was performed on all consecutive prepectoral one-stage breast reconstructions using this technique at a single institution. Patient demographics, mastectomy and reconstruction characteristics, reconstructive outcomes, and cost of support materials were queried and analyzed. Eleven patients (21 breasts) underwent prepectoral immediate implant reconstruction with Vicryl and acellular dermal matrix anterior coverage. Average mastectomy weight was 775.8 g. Smooth, round cohesive implants were used in all cases and average implant size was 514.5 ml. Overall complication rates were low and included one minor infection (4.8 percent) and one case of minor mastectomy flap and partial nipple necrosis each (4.8 percent). Calculated cost savings of Vicryl and acellular dermal matrix anterior coverage was up to $3415 in unilateral and $6830 in bilateral cases. Prepectoral breast reconstruction using acellular dermal matrix inferiorly and Vicryl mesh superiorly is a safe technique that decreases material costs associated with support materials and allows the surgeon to precisely control the implant pocket and position. CLINICAL QUESTION/LEVEL OF EVIDENCE/METHODS:Therapeutic, IV.
PMID: 33620924
ISSN: 1529-4242
CID: 4814962

Deconstructing the Reconstruction: Evaluation of Process and Efficiency in Deep Inferior Epigastric Perforator Flaps

Daar, David A; Salibian, Ara A; Frey, Jordan D; Karp, Nolan S; Choi, Mihye
PMID: 33347084
ISSN: 1529-4242
CID: 4814572

Comparing outcomes between stacked/conjoined and non-stacked/conjoined abdominal microvascular unilateral breast reconstruction

Salibian, Ara A; Bekisz, Jonathan M; Frey, Jordan D; Nolan, Ian T; Kaoutzanis, Christodoulos; Yu, Jason W; Levine, Jamie P; Karp, Nolan S; Choi, Mihye; Thanik, Vishal D
BACKGROUND:Stacked and conjoined free flaps are increasingly utilized in autologous breast reconstruction to augment tissue transfer volume. However, there is a paucity of comparative data on abdominally-based stacked/conjoined versus non-stacked/conjoined flaps. The purpose of this study was to compare ability to match native breast size, complications, recovery, and symmetrizing procedures between these two cohorts in unilateral breast reconstruction. METHODS:A retrospective review of all stacked (two separate hemiabdominal)/conjoined (bipedicled full abdominal) flaps and non-stacked/conjoined (unipedicled hemiabdominal) flaps in unilateral abdominally-based autologous breast reconstructions was performed from 2011 to 2018. Variables including demographics, operative characteristics, complications, and revisions were compared in 36 stacked/conjoined patients versus 146 non-stacked/conjoined patients. RESULTS:The stacked/conjoined cohort had more DIEP flaps (91.7 vs. 65.1%) and the non-stacked/conjoined group more MS-TRAMs (34.2 vs. 6.9%, p = .000). Additionally, non-stacked/conjoined flaps had greater utilization of combined medial and lateral row perforators (p = .000). Mean flap weight was significantly higher than mastectomy weight in stacked/conjoined flaps (+110.7 g) when compared to non-stacked/conjoined flaps (-40.2) (p = .023). Average follow-up was 54.7 ± 27.5 and 54.6 ± 29.3 months, respectively. Stacked/conjoined flaps had lower fat necrosis rates (8.3 vs. 25.4%, p = .039) and had a decreased risk of fat necrosis on multivariable regression analysis (OR 0.278, p = 0.045). There were otherwise no differences in flap, breast, or donor-site complications. Stacked/conjoined flaps also had a lower rate of contralateral breast reduction (p = .041). CONCLUSION/CONCLUSIONS:Stacked/conjoined flaps were associated with a lower risk of fat necrosis compared with non-stacked/conjoined flaps and had a lower rate of contralateral symmetrizing reductions in patients undergoing unilateral abdominally-based breast reconstruction.
PMID: 32997369
ISSN: 1098-2752
CID: 4616942

Optimizing the Mastectomy Flap to Improve Aesthetic Outcomes

Salibian, Ara A; Frey, Jordan D; Choi, Mihye; Karp, Nolan S
The aesthetics of breast reconstruction inherently rely on both the ablative and reconstructive procedures. Mastectomy flap quality remains one of the most critical factors in determining the success of a reconstruction and its aesthetic outcome. Maintaining the segmental perfusion to the nipple and skin envelope during mastectomy requires preserving the subcutaneous tissue superficial to the breast capsule. Because this layer of tissue varies in thickness among different patients and within each breast, anatomic dissection along the appropriate planes is required rather than a "one-size-fits-all" mentality. A team-based approach between the breast surgeon and plastic surgeon will optimize both the ablative and reconstructive procedures while engaging in a process of shared decision-making with the patient. Preoperative clinical analysis and utilization of imaging to assess individual breast anatomy will help guide mastectomies as well as decisions on reconstructive modalities. Critical assessment of mastectomy flaps is paramount and requires flexibility to adapt reconstructive paradigms intraoperatively to minimize the risk of complications and provide the best aesthetic result.
PMID: 33202011
ISSN: 1527-330x
CID: 4684432