Predicting Complications in Breast Reconstruction: Development and Prospective Validation of a Machine Learning Model.

IMPORTANCE: Necrosis of the nipple-areolar complex (NAC) is the Achilles heel of nipple-sparing mastectomy (NSM), and it can be difficult to assess which patients are at risk of this complication (Ann Surg Oncol 2014;21(1):100-106). OBJECTIVE: To develop and validate a model that accurately predicts NAC necrosis in a prospective cohort. DESIGN: Data were collected from a retrospectively reviewed cohort of patients who underwent NSM and immediate breast reconstruction between January 2015 and July 2019 at our institution, a high -volume, tertiary academic center. Preoperative clinical characteristics, operative variables, and postoperative complications were collected and linked to NAC outcomes. These results were utilized to train a random-forest classification model to predict necrosis. Our model was then validated in a prospective cohort of patients undergoing NSM with immediate breast reconstruction between June 2020 and June 2021. RESULTS: Model predictions of NAC necrosis in the prospective cohort achieved an accuracy of 97% (95% confidence interval [CI], 0.89-0.99; P = 0.009). This was consistent with the accuracy of predictions in the retrospective cohort (0.97; 95% CI, 0.95-0.99). A high degree of specificity (0.98; 95% CI, 0.90-1.0) and negative predictive value (0.98; 95% CI, 0.90-1.0) were also achieved prospectively. Implant weight was the most predictive of increased risk, with weights greater than 400 g most strongly associated with NAC ischemia. CONCLUSIONS AND RELEVANCE: Our machine learning model prospectively predicted cases of NAC necrosis with a high degree of accuracy. An important predictor was implant weight, a modifiable risk factor that could be adjusted to mitigate the risk of NAC necrosis and associated postoperative complications.

Adult Cleft Patients: An Exploration of Functional Needs and Treatment Barriers.

BACKGROUND: Management of cleft lip and palate has been well characterized in pediatric patients, but limited data exist regarding the long-term functional outcomes of cleft patients once they reach adulthood. MATERIALS AND METHODS: An institutional, cross-sectional survey of adult patients with a history of cleft lip and/or palate was performed. The survey recorded patient characteristics, concerns, and barriers to care. Patient-reported outcome measures were assessed using the Nasal Obstruction Symptom Evaluation Scale, Epworth Sleepiness Scale, Mandibular Function Impairment Questionnaire, and the CLEFT-Q Speech Modules. RESULTS: A total of 63 patients (18.2%) participated in the survey. The mean patient age was 43.7 years (median: 41 y, range: 19-93 y), and the most common diagnosis was cleft lip and palate (51%) followed by isolated cleft palate (35%) and isolated cleft lip (14%). A subset of patients scored with moderate to severe dysfunction on each outcome measure including the Nasal Obstruction Symptom Evaluation Instrument (59%), Epworth Sleepiness Scale (7%), and Mandibular Function Impairment Questionnaire (13%). Respondent scores on the CLEFT-Q Speech modules demonstrated a bimodal distribution with lower scores in a significant subset of patients with cleft palate and cleft lip and palate. Many respondents (41%) were interested in clinical evaluation but cited barriers to seeking treatment including financial barriers (35%) or lack awareness of clinical options (27%). CONCLUSIONS: Many cleft patients have persistent needs or concerns in adulthood, especially regarding speech and nasal breathing. Systemic barriers pose challenges to these patients undergoing clinical evaluation.

Global Trends in Plastic Surgery on Social Media: Analysis of 2 Million Posts.

BACKGROUND: Plastic surgeons and patients increasingly use social media. Despite evidence implicating its importance in plastic surgery, the large volume of data has made social media difficult to study. OBJECTIVES: The aim of this study was to provide a comprehensive assessment of plastic surgery social media content worldwide by utilizing techniques for analyzing large-scale data. METHODS: The hashtag "#PlasticSurgery" was used to search public Instagram posts. Metadata were collected from posts between December 2018 and August 2020. In addition to descriptive analysis, 2 instruments were created to characterize textual data: a multilingual dictionary of procedural hashtags and a rule-based text classification model to categorize the source of the post. RESULTS: Plastic surgery content yielded more than 2 million posts, 369 million likes, and 6 billion views globally over the 21-month study. The United States had the most posts of 182 countries studied (26.8%, 566,206). Various other regions had substantial presence including Istanbul, Turkey, which led all cities (4.8%, 102,208). The classification model achieved high accuracy (94.9%) and strong agreement with independent raters (κ = 0.88). Providers accounted for 40% of all posts (847,356) and included the categories physician (28%), plastic surgery (9%), advanced practice practitioners and nurses (1.6%), facial plastics (1.3%), and oculoplastics (0.2%). Content between plastic surgery and non-plastic surgery groups demonstrated high textual similarity, and only 1.4% of posts had a verified source. CONCLUSIONS: Plastic surgery content has immense global reach in social media. Textual similarity between groups coupled with the lack of an effective verification mechanism presents challenges in discerning the source and veracity of information.

Do Nipple Necrosis Rates Differ in Prepectoral Versus Submuscular Implant-Based Reconstruction After Nipple-Sparing Mastectomy?

BACKGROUND: Nipple-sparing mastectomy (NSM) has become increasingly popular, given its oncologic safety and preserved nipple areolar complex (NAC) aesthetics. Reconstruction has recently shifted from traditional submuscular (SM) to prepectoral (PP) implant placement. It remains unclear how the plane of implant placement might affect NAC perfusion. Our goal was to assess postoperative outcomes following NSM with SM versus PP implant placement. METHODS: A retrospective single-institution review was performed of all patients undergoing NSM and immediate breast reconstruction in either the PP or SM plane from January 2015 to June 2019. Clinicopathologic details and 90-day complication rates were collected. SM and PP group complications were compared using Chi square analysis. RESULTS: A total of 288 breasts (160 patients) were included, including SM in 79 cases (44 patients) and PP in 209 cases (116 patients). Clinicopathologic features between groups were similar. Overall, the rate of NAC necrosis was 15.1%, with no differences between the SM and PP cohorts (p = 0.79). In cases of NAC necrosis, there was no difference between the SM and PP groups in return to the operating room for debridement (p = 1.0) or explant (p = 0.33). CONCLUSIONS: In our cohort, immediate implant-based reconstruction in the SM and PP planes following NSM was equally safe with respect to postoperative complications and NAC ischemia.

Loss of signalling via Gα13 in germinal centre B-cell-derived lymphoma.

Germinal centre B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common malignancy, yet the signalling pathways that are deregulated and the factors leading to its systemic dissemination are poorly defined. Work in mice showed that sphingosine-1-phosphate receptor-2 (S1PR2), a Gα12 and Gα13 coupled receptor, promotes growth regulation and local confinement of germinal centre B cells. Recent deep sequencing studies of GCB-DLBCL have revealed mutations in many genes in this cancer, including in GNA13 (encoding Gα13) and S1PR2 (refs 5,6, 7). Here we show, using in vitro and in vivo assays, that GCB-DLBCL-associated mutations occurring in S1PR2 frequently disrupt the receptor's Akt and migration inhibitory functions. Gα13-deficient mouse germinal centre B cells and human GCB-DLBCL cells were unable to suppress pAkt and migration in response to S1P, and Gα13-deficient mice developed germinal centre B-cell-derived lymphoma. Germinal centre B cells, unlike most lymphocytes, are tightly confined in lymphoid organs and do not recirculate. Remarkably, deficiency in Gα13, but not S1PR2, led to germinal centre B-cell dissemination into lymph and blood. GCB-DLBCL cell lines frequently carried mutations in the Gα13 effector ARHGEF1, and Arhgef1 deficiency also led to germinal centre B-cell dissemination. The incomplete phenocopy of Gα13- and S1PR2 deficiency led us to discover that P2RY8, an orphan receptor that is mutated in GCB-DLBCL and another germinal centre B-cell-derived malignancy, Burkitt's lymphoma, also represses germinal centre B-cell growth and promotes confinement via Gα13. These findings identify a Gα13-dependent pathway that exerts dual actions in suppressing growth and blocking dissemination of germinal centre B cells that is frequently disrupted in germinal centre B-cell-derived lymphoma.

Clostridium difficile glutamate dehydrogenase is a secreted enzyme that confers resistance to H2O2.

Clostridium difficile produces an NAD-specific glutamate dehydrogenase (GDH), which converts l-glutamate into α-ketoglutarate through an irreversible reaction. The enzyme GDH is detected in the stool samples of patients with C. difficile-associated disease and serves as one of the diagnostic tools to detect C. difficile infection (CDI). We demonstrate here that supernatant fluids of C. difficile cultures contain GDH. To understand the role of GDH in the physiology of C. difficile, an isogenic insertional mutant of gluD was created in strain JIR8094. The mutant failed to produce and secrete GDH as shown by Western blot analysis. Various phenotypic assays were performed to understand the importance of GDH in C. difficile physiology. In TY (tryptose yeast extract) medium, the gluD mutant grew slower than the parent strain. Complementation of the gluD mutant with the functional gluD gene reversed the growth defect in TY medium. The presence of extracellular GDH may have a functional role in the pathogenesis of CDI. In support of this assumption we found higher sensitivity to H2O2 in the gluD mutant as compared to the parent strain. Complementation of the gluD mutant with the functional gluD gene reversed the H2O2 sensitivity.

Characterization of a human cell line stably over-expressing the candidate oncogene, dual specificity phosphatase 12.

BACKGROUND: Analysis of chromosomal rearrangements within primary tumors has been influential in the identification of novel oncogenes. Identification of the "driver" gene(s) within cancer-derived amplicons is, however, hampered by the fact that most amplicons contain many gene products. Amplification of 1q21-1q23 is strongly associated with liposarcomas and microarray-based comparative genomic hybridization narrowed down the likely candidate oncogenes to two: the activating transcription factor 6 (atf6) and the dual specificity phosphatase 12 (dusp12). While atf6 is an established transcriptional regulator of the unfolded protein response, the potential role of dusp12 in cancer remains uncharacterized. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate the oncogenic potential of dusp12, we established stable cell lines that ectopically over-express dusp12 in isolation and determined whether this cell line acquired properties frequently associated with transformed cells. Here, we demonstrate that cells over-expressing dusp12 display increased cell motility and resistance to apoptosis. Additionally, over-expression of dusp12 promoted increased expression of the c-met proto-oncogene and the collagen and laminin receptor intergrin alpha 1 (itga1) which is implicated in metastasis. SIGNIFICANCE: Collectively, these results suggest that dusp12 is oncologically relevant and exposes a potential association between dusp12 and established oncogenes that could be therapeutically targeted.