The activation-induced cytidine deaminase enzyme (AID) is required for somatic hyper-mutation and class switch recombination at the immunoglobulin locus1. In GC-B cells, AID is highly expressed, with inherent mutator activity that helps generate antibody diversity2. However, AID may also regulate gene expression epigenetically by directly deaminating 5-methylcytosine (5mC) in concert with base excision repair to exchange cytosine3. This pathway promotes gene demethylation, thereby removing epigenetic memory. For example, AID promotes active demethylation of the genome in primordial germ cells4. However, different studies have suggested either a requirement5 or a lack of function6 for AID promoting pluripotency in somatic nuclei following fusion with embryonic stem cells (ESCs). We tested directly whether AID regulates epigenetic memory, by comparing the relative ability of cells lacking AID to reprogram from a differentiated cell type to an induced pluripotent stem cell (iPSC). We show that AID-null cells are transiently hyper-responsive to the reprogramming process. Although they initiate expression of pluripotency genes, they fail to stabilize the pluripotent state. The genome of AID-null cells remains hyper-methylated in reprogramming cells, and hyper-methylated genes associated with pluripotency fail to be stably up-regulated, including many MYC target genes. Recent studies identified a late step of reprogramming associated with methylation status7, and implicated a secondary set of pluripotency network components8. AID regulates this late step, removing epigenetic memory to stabilize the pluripotent state.

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Objectives The most common method of performing breast reconstruction after a mastectomy is using tissue expanders. Significant drainage that can lead to seromas and possible infection is a common sequela after mastectomies, and therefore, closed suction drains are routinely placed during the initial surgery (Vardanian et al. Plast Reconstr Surg. 2011;128:403–410). Drains, however, are associated with increased pain and discomfort for the patient and have been attributed to an increased infection rate by some authors (Degnim et al. Ann Surg. 2013;258:240–247; Saratzis et al. Clin Breast Cancer. 2009;9:243–246). We report on our experience using a dual-chamber tissue expander placed in the prepectoral space without acellular dermal matrix or other supportive material, which allows for drainage of periprosthetic fluid and avoids drain placement. Patients and Methods A retrospective, single-institution review of patients' records was performed for all patients who underwent prepectoral tissue expander placement between January 2018 and June 2019. Patients who had drains placed or who underwent autologous reconstruction in combination with expander placement were excluded. Thirty-nine patients were selected, with a total of 66 expander placements. Demographics including body mass index, comorbidities, history of smoking or steroid use, perioperative chemotherapy and radiation therapy, and intraoperative details and indications for surgery were retrospectively collected. Outcomes were separated into minor and major complications. Major complications were defined as complications that required surgical intervention. Results There were 51 prepectoral reconstructions with a dual-chamber tissue expander and no further surgical drain and 15 reconstructions using a standard expander with an additional closed suction drain. Overall complications for the no-drain cohort were 13.7% compared with 20% in the drain cohort (P = 0.68). Surgical site infection rate is 7.84% in the no-drain cohort compared with 13.3% in the drain cohort (P = 0.61). Mean numeric postoperative pain score at 6 hours was 3.2 in the no-drain cohort compared with 4.3 in the drain cohort (P = 0.03) and 4.17 compared with 5.6 at 12 hours, respectively (P = 0.04). Mean time to exchange of implant in the no-drain cohort was 152 days versus 126 days in the drain cohort (P = 0.38). Median follow-up times were 157 days for the no-drain cohort and 347 days for the drain cohort. Conclusions Immediate breast reconstruction using a dual-chamber tissue expander offers a drain-free alternative to the immediate implant-based breast reconstruction. Our infection rate with 7.8% is lower than our own reported rates with subpectoral tissue expander reconstruction using either acellular dermal matrix or poly-4-hydroxybutyrate (17% and 11%). The overall complication rate is similar to historic data associated with breast reconstruction after mastectomy and suggests that dual-chamber expander placement offers a safe alternative possibly decreasing the patient's postoperative pain and discomfort that often is associated with closed suction drains (Saratzis et al. Clin Breast Cancer. 2009;9:243–246).

Background: Advances in surgical technology and adjuvant therapies along with an aging and increasingly morbid U.S. population have led to an increase in complex spine surgery. With this increase comes an elevated risk of complications, including those related to the surgical wound, with some studies demonstrating wound complication incidences approaching 45 percent. The authors hypothesize that immediate muscle flap closure improves outcomes in high-risk patients. Methods: Three hundred one consecutive index cases of spinal wound closure using local muscle flaps performed by the senior author at a single institution between 2006 and 2018 were reviewed. The primary outcome was major wound complication (reoperation and/or readmission because of surgical-site infection, late infection, dehiscence, seroma, or hematoma). Logistic regression analysis was performed to identify predictors of this endpoint. Results: Major wound complications occurred in 6.6 percent of patients (reoperation, 3.6 percent; readmission, 3.0 percent), with a 6.0 percent infection rate and five cases requiring instrumentation removal because of infection. Risk factors identified included radiotherapy (OR, 5.9; p = 0.004), age 65 years or older (OR, 2.8; p = 0.046), and prior spine surgery (OR, 4.3; p = 0.027). The incidence of major wound complication increased dramatically with each additional risk factor. Mean drain dwell duration was 21.1 ± 10.0 days and not associated with major wound complications, including infection (OR, 1.04; p = 0.112). Conclusions: Immediate local muscle flap closure following complex spine surgery on high-risk patients is associated with an acceptable rate of wound complications and, as these data demonstrate, is safe and effective. Consideration should be given to immediate muscle flap closure in appropriately selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.