Protein engineering a PhotoRNR chimera based on a unifying evolutionary apparatus among the natural classes of ribonucleotide reductases.

Ribonucleotide reductases (RNRs) are essential enzymes that catalyze the de novo transformation of nucleoside 5'-di(tri)phosphates [ND(T)Ps, where N is A, U, C, or G] to their corresponding deoxynucleotides. Despite the diversity of factors required for function and the low sequence conservation across RNRs, a unifying apparatus consolidating RNR activity is explored. We combine aspects of the protein subunit simplicity of class II RNR with a modified version of Escherichia coli class la photoRNRs that initiate radical chemistry with light to engineer a mimic of a class II enzyme. The design of this RNR involves fusing a truncated form of the active site containing α subunit with the functionally important C-terminal tail of the radical-generating ß subunit to render a chimeric RNR. Inspired by a recent cryo-EM structure, a [Re] photooxidant is located adjacent to Y356[ß], which is an essential component of the radical transport pathway in class I RNRs. Combination of this RNR photochimera with cytidine diphosphate (CDP), adenosine triphosphate (ATP), and light resulted in the generation of Y356• along with production of deoxycytidine diphosphate (dCDP) and cytosine. The photoproducts reflect an active site chemistry consistent with both the consensus mechanism of RNR and chemistry observed when RNR is inactivated by mechanism-based inhibitors in the active site. The enzymatic activity of the RNR photochimera in the absence of any ß metallocofactor highlights the adaptability of the 10-stranded αß barrel finger loop to support deoxynucleotide formation and accommodate the design of engineered RNRs.

Zinc cluster transcription factors frequently activate target genes using a non-canonical half-site binding mode.

Gene expression changes are orchestrated by transcription factors (TFs), which bind to DNA to regulate gene expression. It remains surprisingly difficult to predict basic features of the transcriptional process, including in vivo TF occupancy. Existing thermodynamic models of TF function are often not concordant with experimental measurements, suggesting undiscovered biology. Here, we analyzed one of the most well-studied TFs, the yeast zinc cluster Gal4, constructed a Shea-Ackers thermodynamic model to describe its binding, and compared the results of this model to experimentally measured Gal4p binding in vivo. We found that at many promoters, the model predicted no Gal4p binding, yet substantial binding was observed. These outlier promoters lacked canonical binding motifs, and subsequent investigation revealed Gal4p binds unexpectedly to DNA sequences with high densities of its half site (CGG). We confirmed this novel mode of binding through multiple experimental and computational paradigms; we also found most other zinc cluster TFs we tested frequently utilize this binding mode, at 27% of their targets on average. Together, these results demonstrate a novel mode of binding where zinc clusters, the largest class of TFs in yeast, bind DNA sequences with high densities of half sites.

MicroRNA-206 as a Potential Cholesterol-lowering Drug is Superior to Statins in Mice.

Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis and fecal neutral steroid excretion. CONCLUSIONS: MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.

We've all been wrong about provisional tic disorder.

BACKGROUND: Provisional Tic Disorder (PTD) is common in childhood. The received wisdom among clinicians is that PTD is short-lived and mild, with at most a few tics, and rarely includes complex tics, premonitory phenomena or comorbid illnesses. However, such conclusions come from clinical experience, with biased ascertainment and limited follow-up. METHODS: Prospective study of 89 children with tics starting 0-9 months ago (median 4 months), fewer than half from clinical sources. Follow-up at 12 (± 24, 36, 48) months after the first tic. RESULTS: At study entry, many children had ADHD (39), an anxiety disorder (27), OCD (9) or enuresis (17). All had at least two current tics, with a mean total since onset of 6.9 motor and 2.0 phonic tics. Forty-one had experienced a complex tic, and 69 could suppress some tics. Tics were clinically meaningful: 64 had tics severe enough for a clinical trial, and 76 families sought medical attention for the tics. At 12 months, 79 returned, and 78 still had tics. Of these, 29 manifested no tics during history and extended examination, but only via audio-visual monitoring when the child was seated alone. Only 12/70 now had plans to see a doctor for tics. Most who returned at 2-4 years still had tics known to the child and family, but medical impact was low. CONCLUSIONS: Our results do not contradict previous data, but overturn clinical lore. The data strongly argue against the longstanding but arbitrary tradition of separating tic disorders into recent-onset versus chronic.

Indocyanine Green Angiography for Detecting Quantitative Perfusion Changes in Deep Inferior Epigastric Perforator Flap Breast Reconstruction With Second Venous Drainage.

BACKGROUND: This study aims to compare perfusion dynamics using indocyanine green videoangiography before and after the creation of a second venous anastomosis between the superficial inferior epigastric vein and the retrograde internal mammary vein (IMV) in deep inferior epigastric perforator (DIEP) flap breast reconstructions. METHODS: Indocyanine green videoangiography performed during DIEP flap reconstructions was analyzed prospectively. The areas of interest were above the perforators with the highest intensity (complete perfusion), the most distal lateral edge of the flap (partial perfusion), and the next lowest intensity (ischemic). We compared the zone intensities before and after the second venous anastomosis, assessing venous drainage patency and functionality. Patient characteristics, operative details, and complications were collected. RESULTS: Seven patients (10 breasts) underwent DIEP reconstruction. Mean age was 54.5 ± 12.4 years. Mean operative duration was 575.5 ± 172.6 minutes. Donors included DIEV (n = 10, 100.0%), superficial inferior epigastric vein (n = 9, 90.0%), and superficial circumflex epigastric vein (n = 1, 10.0%). All DIEVs were anastomosed to the antegrade IMV (n = 10, 100.0%). Superficial inferior epigastric veins were anastomosed to the retrograde IMV (n = 10, 100.0%). Mean peak intensities of the complete perfusion zone before and after the second venous anastomosis were 160.7 ± 42.1 and 188 ± 42.1, respectively (P = 0.163). Mean peak intensities of the partial perfusion zone were 100.8 ± 21.5 and 152 ± 31.5, respectively (P < 0.001). Mean peak intensities of the ischemic zone were 90.4 ± 37.4 and 143.4 ± 45.3, respectively (P = 0.012). CONCLUSION: These findings highlight the potential benefits of the super drainage technique in enhancing perfusion and reducing complications, emphasizing the need for further investigation and consideration of this technique in clinical practice.

Acellular Dermal Matrix-Assisted, Prosthesis-Based Breast Reconstruction: A Comparison of SurgiMend PRS, AlloDerm, and DermACELL.

BACKGROUND: Acellular dermal matrices (ADMs) are frequently employed in immediate prosthesis-based breast reconstruction (iPBR) to provide structural support. Despite differences in ADM derivatives, few studies directly compare their outcomes in the setting of iPBR. We sought to conduct a large head-to-head study comparing 3 ADMs used across our institution. METHODS: A multicenter retrospective review of patients undergoing iPBR with SurgiMend PRS (fetal bovine-derived; Integra Lifesciences, Princeton, NJ), AlloDerm (human-derived; LifeCell Corp, Bridgewater, NJ), or DermACELL (human-derived; Stryker Corp, Kalamazoo, MI) between January 2014 to July 2022 was performed. Primary outcomes included rates of unplanned explantation and total reconstructive failure. Secondary outcomes included 90-day postoperative complications and long-term rates of capsular contracture development. RESULTS: A total of 738 patients (1228 breasts) underwent iPBR during the study period; 405 patients received DermACELL (54.9%), 231 received AlloDerm (31.3%), and 102 received SurgiMend PRS (13.8%). Rates of short-term complications, total reconstruction failure, reoperation within 90 days, capsular contracture, and unplanned explantation were comparable. These findings remained true upon multivariate analysis accounting for baseline differences between cohorts, whereby ADM type was not an independent predictor of any outcome of interest. Conversely, factors such as body mass index, diabetes mellitus, smoking history, neoadjuvant and adjuvant chemotherapy, adjuvant radiation, skin-sparing mastectomy, Wise pattern and periareolar incisions, use of tissue expanders, and a subpectoral plane of insertion were significant predictors of postoperative complications. CONCLUSION: Low rates of complications support the equivalency of fetal bovine and human-derived ADMs in iPBR. Patient characteristics and operative approach are likely more predictive of postoperative outcomes than ADM derivative alone.

Expanded Indications for Nipple-Sparing Mastectomy and Immediate Breast Reconstruction in Patients Older Than 60 Years.

INTRODUCTION: Although nipple-sparing mastectomy (NSM) and immediate breast reconstruction (IBR) have long been praised for excellent cosmetic results and the resultant psychosocial benefits, the feasibility and safety of these procedures in patients older than 60 years have yet to be demonstrated in a large population. METHODS: Patients undergoing NSM with or without IBR at the MedStar Georgetown University Hospital between 1998 and 2017 were included. Patient demographics, surgical intervention, and complication and recurrence events were retrieved from electronic medical records. Primary outcomes were recurrence and complication rates by age groups older and younger than 60 years. RESULTS: There were 673 breasts from 397 patients; 58 (8.6%) older than 60 years and 615 (91.4%) younger than 60 years with mean follow-up of 5.43 (0.12) years. The mean age for those older than 60 was 63.9 (3.3) years, whereas that for those younger than 60 was 43.1 (7.9) years (P < 0.001). The older than 60 group had significantly higher prevalence of diabetes, rates of therapeutic (vs prophylactic) and unilateral (vs bilateral) NSM, and mastectomy weight. However, there were no significant differences by age group in complication rates or increased risk of locoregional or distant recurrence with age. CONCLUSIONS: Based on similar complication profiles in both age groups, we demonstrate safety and feasibility of both NSM and IBR in the aging population. Despite increased age and comorbidity status, appropriately selected older women were able to achieve similar outcomes to younger women undergoing NSM with or without IBR.

Radical Transport Facilitated by a Proton Transfer Network at the Subunit Interface of Ribonucleotide Reductase.

Ribonucleotide reductases (RNRs) play an essential role in the conversion of nucleotides to deoxynucleotides in all organisms. The Escherichia coli class Ia RNR requires two homodimeric subunits, α and ß. The active form is an asymmetric αα'ßß' complex. The α subunit houses the site for nucleotide reduction initiated by a thiyl radical (C439•), and the ß subunit houses the diferric-tyrosyl radical (Y122•) that is essential for C439• formation. The reactions require a highly regulated and reversible long-range proton-coupled electron transfer pathway involving Y122•[ß] ↔ W48?[ß] ↔ Y356[ß] ↔ Y731[α] ↔ Y730[α] ↔ C439[α]. In a recent cryo-EM structure, Y356[ß] was revealed for the first time and it, along with Y731[α], spans the asymmetric α/ß interface. An E52[ß] residue, which is essential for Y356 oxidation, allows access to the interface and resides at the head of a polar region comprising R331[α], E326[α], and E326[α'] residues. Mutagenesis studies with canonical and unnatural amino acid substitutions now suggest that these ionizable residues are important in enzyme activity. To gain further insights into the roles of these residues, Y356• was photochemically generated using a photosensitizer covalently attached adjacent to Y356[ß]. Mutagenesis studies, transient absorption spectroscopy, and photochemical assays monitoring deoxynucleotide formation collectively indicate that the E52[ß], R331[α], E326[α], and E326[α'] network plays the essential role of shuttling protons associated with Y356 oxidation from the interface to bulk solvent.

The Characteristics and Ethics of Sham Surgeries: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: We sought to perform a large-scale systematic review across all sham-controlled studies currently present in the literature to better characterize the ethical considerations of these studies. BACKGROUND: Innovative surgical procedures are often introduced into the clinical setting without the robust clinical trials required for medicinal treatments. Sham surgeries serve as placebos by performing all steps of a surgical intervention aside from those deemed therapeutically necessary. Yet, sham trials are underutilized because of ethical controversy. METHODS: Ovid MEDLINE was queried through April 2022 with combinations of the Medical Subject (MeSH) headings and keywords including, but not limited to, "surgery," "endoscopy," "randomized controlled trial," and "sham procedure." Primary outcomes were surgical indications and characteristics, outcome measurements, and whether the investigational treatment was offered to the sham cohort. RESULTS: One hundred seventy-two articles fit our inclusion criteria, with gastrointestinal pathologies being the most common surgical indication. Participants, personnel, and outcome assessment were all blinded in 8.7% of trials (n=15). Study populations included adult subjects (age ≥18) in 170 studies (98.8%), and two involved children. The most common level of dissection and type of anesthesia were deep (n=66, 38.4%) and general (n=49, 28.5%), respectively. An open surgical approach was utilized in 20.9% of studies (n=36). Primary outcomes were objective in 75 studies (43.6%) and subjective in 97 (56.4%), 62 of which used validated outcome measures (36.0%). Four trials explicitly did not offer the surgery to the sham arm (2.3%), whereas 106 had no mention of whether the intervention was offered (61.6%). CONCLUSIONS: Our systematic review of 172 randomized, sham-controlled trials highlights the ethical considerations that must be considered in these studies, namely the importance of transparent study design and objective outcome reporting, the difficulty of informed consent, and the inherent risks associated with surgical interventions.

Nipple-Sparing Mastectomy With Immediate Reconstruction After Breast-Conserving Therapy and Radiation: Complications and Oncologic Safety.

INTRODUCTION: Nipple-sparing mastectomy (NSM) offers improved, patient-centered outcomes with demonstrated oncologic safety ( Ann Surg Oncol 2020;27:344-351). Indications for NSM continue to expand to patients outside of the traditional eligibility criteria, including those with prior breast-conserving therapy (BCT) with radiotherapy. Currently, limited data exist evaluating both short- and long-term outcomes in patients proceeding to NSM after prior BCT. METHODS: All patients undergoing bilateral NSM in a single institution from 2002 through 2017 with history of prior BCT were included in the final cohort, without exclusions. A retrospective chart review was performed to identify patient demographics, operative details, and complications. Outcomes assessed included early complications (<30 days from NSM), late complications (>30 days), rates of prosthetic failure, unplanned reoperations, and reconstructive failures, as well as oncologic safety. Student t , χ 2 , and Fisher exact tests were used to analyze outcomes of paired (BCT vs non-BCT) breasts within each patient. RESULTS: A total of 17 patients undergoing 34 NSMs were included. Each had a history of BCT and either ipsilateral breast recurrence (64.7%), risk-reducing NSM (23.5%), or a new contralateral primary cancer (11.8%). The cohort had a mean age of 51.1 years. With regard to acute complications (ischemia, infection, nipple-areolar complex or flap ischemia or necrosis, and wound dehiscence), there was no significant difference noted between breasts with prior BCT versus no prior BCT overall (41.2% vs 35.3%, respectively; P = 0.724). Complications occurring after 30 days postoperatively (capsular contracture, contour abnormality, animation deformity, bottoming out, rotation, and rippling) in prior BCT breasts versus no prior BCT had no significant differences overall (58.8% vs 41.2% respectively; P = 0.303). The mean follow-up was 5.5 years, during which no patients had a reported locoregional or distant recurrence in either breast. CONCLUSIONS: No significant differences in early or late complications were identified between breasts in patients undergoing bilateral NSM with a history of unilateral BCT and XRT. In the 5.5 years of follow-up, there were no recurrences, lending support to NSM for management of recurrent disease in addition to National Comprehensive Cancer Network-recommended total mastectomy. We propose that NSM should not be contraindicated in patients exposed to radiation with BCT.

Facial Hypertrophy as a Complication of Weight Gain in Autologous Fat Graft Patients: Considerations and Recommendations.

Fat grafting can restore facial volume for reconstructive and cosmetic indications. Common practice often involves extracting lipoaspirate from the most abundant anatomic location. However, grafted fat retains the phenotypic characteristics of its original location and can undergo exaggerated hypertrophy with patient weight fluctuations. The aim of this study was to systematically assess the literature to summarize the reported effects of postoperative weight gain on facial hypertrophy in patients after facial fat grafting and to determine potentially avoidable factors. A search through PubMed/MEDLINE was conducted on October 4, 2022, to identify relevant articles with appropriate search terms. No lower date limit was applied and all eligible nonanimal clinical articles in English were included for review. Reports were summarized and presented as descriptive statistics. The search generated 714 articles. After abstract and full-text review of the initial set of articles, 6 were included in our analysis. All articles described poor cosmetic outcomes resulting from nonanatomic hypertrophy of the grafted fat. None of the articles reported a thorough methodology for selecting the donor site to minimize fat hypertrophy with potential future weight fluctuations. Grafted facial fat is susceptible to exaggerated hypertrophy as a result of changes in patient weight. Specifically, harvesting lipoaspirate from maximally abundant areas of the body may increase this risk. Individualizing the area of fat donation may attenuate unwanted fat growth and further contribute to increased patient quality of life.

A case of histiocytoid angiosarcoma mimicking Rosai-Dorfman disease histopathologically.

There are very few documented cases of histiocytoid angiosarcoma in the literature. We report a rare case of histiocytoid angiosarcoma demonstrating emperipolesis, a histopathologic finding that mimics Rosai-Dorfman disease (RDD). A 77-year-old male presented with a subcutaneous nodule on his left forehead. Microscopic examination of the tumor revealed a dense lymphohistiocytic and plasmacytic infiltrate with large epithelioid cells, many of which showed abundant pale eosinophilic to foamy-appearing cytoplasm, and some of which displayed phagocytosis of intact inflammatory cells and erythrocytes. The tumor also showed significant cytologic atypia and pleomorphism. Immunohistochemical stains showed strong staining of the histiocytoid cells and focal anastomosing-like vascular spaces for CD31 and ERG-1, but were essentially negative for CD68, lysozyme, CD163, S100, and CD1a, consistent with a vascular endothelial tumor. This case expands the spectrum of findings that can be identified in angiosarcomas, and should help to prevent potential misdiagnosis as a less aggressive tumor such as RDD.

Preserving Nipple Sensitivity after Breast Cancer Surgery: A Systematic Review and Meta-Analysis.

Purpose: As breast-conserving procedures become increasingly safe and viable options for surgical management of breast cancer, efforts have focused on assessing and optimizing patient-reported outcome measures (PROMs), such as nipple sensation. This study aims to evaluate the current understanding of nipple-areolar complex (NAC) sensation outcomes in breast cancer patients undergoing breast cancer surgeries, namely, nipple-sparing mastectomies (NSM), skin-sparing mastectomies (SSM), and lumpectomies. Methods: Articles including terms related to "nipple," "mastectomy," "sensation," and "patient-reported outcome" were queried from three databases according to PRISMA guidelines. Study characteristics, patient demographics, and surgical details were recorded. Outcomes of interest included objective nipple sensitivity testing and PROMs. Results: Of 888 manuscripts identified, 28 articles met the inclusion criteria. Twelve studies (n = 578 patients) used objective measures to evaluate sensitivity, such as monofilament testing. Sixteen studies (n = 1785 patients) assessed PROMs through validated or investigator-generated surveys. Three of the included studies reported NAC sensitivity in patients who received NSM with neurotization (n = 203 patients) through a variety of techniques that used various grafts to coapt a lateral intercostal nerve to the NAC nerve stumps. Results of investigator surveys showed that of 1565 patients without neurotization, nipple sensation was maintained in 29.0% (n = 453) of patients. Of 138 NSM patients without NAC neurotization, SWM testing showed an average loss of protective sensation in the nipple (average SWM score: 4.7) compared to normal or diminished sensation to light touch in nonoperated controls (average SWM score: 2.9, n = 195). Of patients who underwent NSM with neurotization, one study (n = 78) reported maintenance of NAC sensation in 100% of patients, while another study (n = 7) reported average diminished protective sensation in the nipple (average SWM score: 3.9). Conclusion: Our study has shown that objective and patient-reported results of nipple sensitivity support nipple-sparing techniques as a viable option for preserving NAC sensation, although patients can expect a decrease in sensation overall. Neurotization of the NAC during NSM shows promising results of improved postoperative nipple sensitivity, though additional studies are warranted to confirm this finding. Variations between study methodologies highlight the lack of standardization in sensory testing techniques when evaluating NAC sensation.

Bacitracin for Injection Recall: Impact on Immediate Breast Implant Surgical Outcomes.

Background: Triple-antibiotic irrigation of breast implant pockets is a mainstay of infection prophylaxis in breast reconstruction and augmentation. The recall of bacitracin for injection due to risk of anaphylaxis and nephrotoxicity in January 2020, a staple component of the irrigation solution, has raised concern for worsened postoperative sequelae. This study aimed to investigate pre- and post-recall implant-based breast surgery to analyze the impact of bacitracin in irrigation solutions on infection rates. Methods: All implant-based breast reconstruction or augmentation surgeries from January 2019 to February 2021 were retrospectively reviewed. In a regression discontinuity study design, patients were divided into pre- and post-recall groups. Patient demographics, surgical details, and outcomes including infection rates were collected. Differences in complication rates were compared between groups and with surgical and patient factors. Results: 254 implants in 143 patients met inclusion criteria for this study, with 172 implants placed before recall and 82 placed after recall. Patients in each cohort did not differ in age, BMI, smoking status, or history of breast radiation or capsular contracture (p > 0.05). All breast pockets were irrigated with antibiotic solution, most commonly bacitracin, cefazolin, gentamycin, and povidone-iodine before recall (116,67.4%) and cefazolin, gentamycin, and povidone-iodine after recall (59,72.0%). There was no difference in incidence of infection (6.4% vs. 8.5%, p=0.551) or cellulitis (3.5% vs. 3.7%, p=0.959) before and after recall. Implant infection was associated with smoking history (p < 0.001) and increased surgical time (p=0.003). Conclusions: Despite the recent recall of bacitracin from inclusion in breast pocket irrigation solutions, our study demonstrated no detrimental impact on immediate complication rates. This shift in irrigation protocols calls for additional investigations into optimizing antibiotic combinations in solution, as bacitracin is no longer a viable option, to improve surgical outcomes and long-term benefits.

Postmastectomy Reconstruction in Male Breast Cancer.

Introduction: Less than 1% of all breast cancers are diagnosed in males. In females, postmastectomy breast reconstruction is associated with increased patient satisfaction. However, there is a paucity of literature describing reconstructive options for postmastectomy deformity in the male chest. The purpose of this systematic review was to evaluate postmastectomy reconstruction outcomes in males with breast cancer. Methods: A systematic review was performed in accordance with PRISMA guidelines. Ovid MEDLINE, Embase, Cochrane, and Web of Science were queried for records pertaining to the study question using medical subject heading (MeSH) terms such as "male breast cancer," "mastectomy," and "reconstruction." No limitations were placed on the year of publication, country of origin, or study size. Study characteristics and patient demographics were collected. Primary outcomes of interest included postoperative complications, recurrence rate, and mortality rate. Results: A total of 11 articles examining 29 male patients with breast cancer who underwent postmastectomy reconstruction were included for analysis. Literature was most commonly available in the form of case reports. The average age was 59.6 +/-11.4 years. Reconstruction methods included fat grafting (n = 1, 3.4%), silicone implants (n = 1, 3.4%), and autologous chest wall reconstruction with local flaps (n = 26, 89.7%). Postoperative complications occurred in two patients (6.8%), including partial nipple necrosis (n = 1) and hypertrophic scarring (n = 1). Of the studies reporting patient satisfaction, all patients were pleased with the aesthetic appearance of their chest. Conclusion: This systematic review revealed the limited availability of research regarding postmastectomy chest reconstruction in males with breast cancer. Nevertheless, the evidence available suggests that reconstruction can restore a patient's body image and, thus, should be regularly considered and discussed with male patients. Larger studies are warranted to further shed light on this population.

A Critical Appraisal of Late Complications of Prepectoral versus Subpectoral Breast Reconstruction Following Nipple-Sparing Mastectomy.

BACKGROUND: Nipple-sparing mastectomy (NSM) offers improved aesthetics without compromising oncologic safety. Subpectoral breast reconstruction has long been standard practice, although prepectoral reconstruction has recently resurged in popularity. Due to this recent paradigm shift, studies comparing long-term outcomes by reconstructive plane are lacking. METHODS: A retrospective review was conducted on consecutive NSMs with implant-based reconstruction in either the prepectoral or subpectoral plane from 2014 to 2018. Patient demographics, implant specifications, and operative details were collected to evaluate primary outcomes of prosthetic failure and unplanned reoperations by reconstructive plane. Secondary outcomes included animation deformity, capsular contracture, rippling, plane change, and minor revisions, including fat grafting. Bivariate and multivariate analyses were performed to assess outcomes. RESULTS: Overall, 405 NSMs were performed on 228 women (subpectoral = 202, prepectoral = 203), with a mean follow-up of 2.1 years (standard deviation 1.1). During the study period (2014-2018), a shift from subpectoral to predominantly prepectoral mastectomies occurred in 2017. Prepectoral reconstructions were more often direct-to-implant (DTI) compared with subpectoral (73.9% vs. 33.2%, p < 0.001). Prepectoral reconstruction demonstrated significantly reduced prosthetic failure (odds ratio [OR] 0.30, 95% confidence interval [CI] 0.14-0.65) and unplanned reoperations (OR 0.43, 95% CI 0.24-0.77) compared with subpectoral reconstruction after controlling for implant characteristics and other possible confounders. Prepectoral patients experienced decreased animation deformity overall (19.7% vs. 0.0%, p < 0.001), with plane changes seen in 10.6% of subpectoral reconstructions for animation deformity correction. Prepectoral patients experienced an increase in rippling (15.3% vs. 6.1%, p = 0.003) without a significant increase in fat grafting (subpectoral = 11.6% vs. prepectoral = 12.3%, p = 0.829). CONCLUSIONS: This single-institution experience compares late complications of prepectoral and subpectoral implant-based reconstruction following NSM. Prepectoral reconstruction can be safely performed with improved understanding of mastectomy planes, readily affords DTI reconstruction, and reduces animation deformity at the expense of rippling.

Delivery of nipple-sparing mastectomy within a single healthcare system: The impact of provider preferences.

Nipple-sparing mastectomy (NSM) offers superior esthetic outcomes without sacrificing oncologic safety for select patients requiring mastectomy. While disparities in oncologic care are well established, no study to date has investigated equitable delivery of the various mastectomy types. The objective of this study is to examine multilevel factors related to the distribution of NSM. Patients undergoing mastectomy between 2014 and 2018 across eight hospitals in a single healthcare system were retrospectively reviewed. Patients were categorized by mastectomy type-NSM or other mastectomy (OM). Patient information such as age, race, comorbidities, and median income by ZIP code was collected. Disease characteristics, such as mastectomy weight, breast cancer stage, and treatment history, were identified. Provider and system-level variables, such as specific provider, hospital of operation, and insurance status, were determined. Bivariate analysis was used to identify variables for inclusion in a backward multivariable model. A cohort of 1202 mastectomy patients was identified, with 388 receiving NSM. The average age was 55.8 years (NSM: 48.8, OM: 59.1, P < .001). 39.8% of white patients (n = 242) and 20.0% of African American patients (n = 88) received NSM (P < .001). Average mastectomy weight was 384.3 (SD 195.7) in the NSM group, compared to 839.4 (SD 521.1) in the OM group (P < .001). 41.4% (n = 359) of patients treated at academic centers, and 6.9% (n = 21) of patients treated at community centers received NSM (P < .001). In the multivariate model, the factor with the largest impact on NSM was specific provider. Odds of NSM decreased by 76%-88% for certain surgeons, while odds increased by 63 times for one surgeon. This study utilizes a large multi-institutional database to highlight disparities in NSM delivery. Expectedly, younger, relatively healthy patients, with smaller breast size were more likely to undergo NSM, in accordance with surgical guidelines. However, when all other factors were controlled, provider preferences played the most significant role in NSM delivery rates. These findings demonstrate the need for practice reexamination to ensure equitable access to NSM.

A Head-to-Head Comparison of the Medial Sural Artery Perforator versus Radial Forearm Flap for Tongue Reconstruction.

BACKGROUND: For tongue reconstruction, the radial forearm flap (RFF) is commonly used. In the last decade, the medial sural artery perforator (MSAP) flap has been successfully used with reportedly superior donor-site outcomes. Our study is the first to compare the RFF and MSAP for reconstruction of partial glossectomy defects (<50% of tongue). METHODS: We conducted a retrospective review of 20 patients with partial glossectomy defects reconstructed at a tertiary referral center. Patient demographics, perioperative data, and postoperative complications were analyzed. Objective measures of speech, swallowing, and subjective patient satisfaction with their donor site were recorded. RESULTS: Ten RFF and MSAP were each used, with a mean partial glossectomy defect size of 40.5 and 43.5%, respectively. The MSAP was significantly thicker (7.8 vs. 4.3 mm, p < 0.05) with a longer harvest time (122.5 vs. 75.0 minutes, p < 0.05). There were no cases of free flap failure. Donor-site healing times were comparable, but the MSAP group experienced significantly less donor-site complications (n = 1 vs. n = 7, p < 0.05). Functional outcomes were comparable with 13 patients achieving normal speech and diet after 3 months (MSAP = 6 vs. RFF = 7, p = 1.00). All patients were satisfied with their donor-site outcome with the MSAP group having a marginally higher score. CONCLUSION: Both flaps are good options for partial glossectomy reconstruction. Though more challenging to harvest, the MSAP gives comparable functional results and has become our first reconstructive option given its superior donor-site outcomes.

Patient Representation and Diversity in Plastic Surgery Social Media.

BACKGROUND: Plastic surgeons increasingly use social media as a means for patient engagement, trainee education, and research dissemination. Appropriate patient diversity on these platforms is critical to promote interaction with all patients and ensure adequate training of plastic surgeons to work with diverse populations. OBJECTIVES: This study aimed to assess patient representation, particularly of racial and ethnic groups, among plastic surgery Instagram accounts. METHODS: Nine Instagram accounts of plastic surgery journals and professional organizations were analyzed for posts containing patient images between April 2015 and June 2020. Each unique patient image was assessed for demographic factors. Skin tone was analyzed as a proxy for racial diversity, with Fitzpatrick scale scores of 1 to 3 indicating white and 4 to 6 indicating nonwhite. Univariate analysis was performed to determine differences in representation. RESULTS: A total of 6719 posts from 5 journal and 4 professional organization accounts were found to contain 2547 unique patient images. Overall, 88.14% of patient images had white skin tone, whereas only 11.86% displayed nonwhite skin tone. Cosmetic procedure patient images had a higher frequency of white skin tone than reconstruction images (89.93% vs 81.98%, P < 0.001). When compared with US Census data and the ASPS Annual Report data on race of patients undergoing plastic surgery, our data revealed significant underrepresentation of patients of color on social media (P < 0.001). CONCLUSIONS: This study highlights the underrepresentation of patients of color within social media imagery. Equitable representation of patients on social media is important to decrease patient barriers to healthcare and improve physician training to engage with diverse populations.

CLIC4 abrogation promotes epithelial-mesenchymal transition in gastric cancer.

Chloride intracellular channel protein 4 (CLIC4) has been implicated in different types of cancers, but the role of CLIC4 in the development of gastric cancer (GC) remains unknown. We analyzed the expression of CLIC4 in 102 pairs of gastric adenocarcinomas by western blot and real-time PCR. Our data revealed that the expression of CLIC4 is reduced in GC tumor tissues compared with adjacent normal tissues. The expression levels of CLIC4 correlate inversely with the clinical stage of GC. CLIC4 expression is lowest in MKN45 cells, which have the highest tumorigenic potential and express the highest levels of cancer stem cell markers CD44 and OCT4, compared with N87 and AGS cells. Exogenous overexpression of CLIC4 downregulated the expression of CD44 and OCT4, and inhibited migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, anchorage-independent growth of GC cells was decreased and the cells became more sensitive to 5-fluorouracil and etoposide treatment when CLIC4 was overexpressed. The ability of N87 cells to form tumors in nude mice was enhanced when CLIC4 was silenced. We, for the first time, demonstrate that CLIC4 suppresses tumor growth by inhibiting cancer cell stemness and EMT.