PurposeWe evaluated prevention of transforming growth factor β (TGFβ)–induced transdifferentiation of cultured scleral fibroblasts to myofibroblasts by rho-associated protein kinase (ROCK) inhibitors. Additionally, we tested whether local delivery of ROCK inhibitors reduced scleral fibroblast proliferation in response to chronic intraocular pressure (IOP) elevation.MethodsPrimary human peripapillary sclera (PPS) fibroblasts were cultured and treated with TGFβ to induce myofibroblast transdifferentiation, as determined by immunoblot assessment of α smooth muscle actin (SMA) levels and collagen gel contraction. Cells were treated with the ROCK inhibitors Y27632, fasudil, and H1152 before TGFβ treatment. ROCK activity in TGFβ-treated fibroblasts and sclera from ocular hypertensive mice was assessed by measuring phosphorylation of the ROCK substrate MYPT1 at Thr696. Fibroblast proliferation following IOP elevation and ROCK inhibitor treatment was assessed by an enzyme-linked immunosorbent (ELISA) assay.ResultsROCK inhibitors H1152 (10μM), Y27632 (10 μM), and fasudil (5μM) reduced SMA expression 72%, 85%, and 68%, respectively. Collagen gel contraction was reduced by 36% (P < 0.001), 27% (P = 0.0003), and 33% (P = 0.0019) following treatment with fasudil (25 μM), Y27632 (10 μM), and H1152 (10μM). ROCK activity induced by TGFβ rose 4.74 ± 1.9 times over control at 4 hours (P = 0.0004) and 2.4 ± 0.47-fold (P = 0.0016) in sclera after IOP elevation. Proliferation of scleral fibroblasts after chronic IOP elevation was reduced 77% by Y27632 (P = 0.001) and 84% by fasudil (P = 0.0049).ConclusionsROCK inhibitors reduce TGFβ-induced myofibroblast transdifferentiation and glaucoma-induced scleral cell proliferation.Translational RelevanceThese findings suggest altered fibroblast activity promoted by ROCK inhibitors could modify scleral biomechanics and be relevant to glaucoma treatment.
Background The COVID-19 pandemic has led to the widespread adoption of video calling. A parallel growth in aesthetic surgery demand has been documented. Objectives To identify associations between video call engagement and aesthetic surgery attitudes. Methods We distributed a cross-sectional survey via Amazon Mechanical Turk in November 2020. Respondents were asked to report their time spent video calling, video calling applications and features (eg, virtual backgrounds) they used, and aesthetic surgery attitudes using the 15-item Acceptance of Cosmetic Surgery Scale (ACSS; higher scores indicate greater acceptance). We compared ACSS scores between video call users and non-users using Student’s t-tests. We used Pearson’s correlation coefficient to quantify associations between ACSS scores and time spent on calls and multivariable analysis to estimate associations between video call engagement and ACSS scores. Results A total of 295 respondents (mean age, 37.6; 49.5% female) completed the survey. Across all video call applications surveyed, video call users had higher ACSS scores than non-users. Increased time respondents spent looking at their own face on video call was moderately associated with higher ACSS scores (r=0.48, P<0.01), while time spent looking at another person’s face was not associated with a change in ACSS scores (r=0.09, P=0.11). Increased video call use was associated with higher ACSS scores. Conclusions Increased video calling use is associated with increased acceptance of aesthetic surgery. Although the clinical significance of ACSS scores can be better elucidated, plastic surgeons should consider the effects of video calling on patient motivations for aesthetic surgery in the COVID-19 era.
The purpose of this study was to describe the cellular architecture of normal human peripapillary sclera (PPS) and evaluate surface topography's role in fibroblast behavior. METHODS.PPS cryosections from nonglaucomatous eyes were labelled for nuclei, fibrillar actin (FA), and alpha smooth muscle actin (αSMA) and imaged. Collagen fibrils were imaged using second harmonic generation. Nuclear density and aspect ratio of the internal PPS (iPPS), outer PPS (oPPS), and peripheral sclera were determined. FA and αSMA fibril alignment with collagen extracellular matrix (ECM) was determined. PPS fibroblasts were cultured on smooth or patterned membranes under mechanical strain and in the presence of TGFβ1 and 2. RESULTS.The iPPS (7.1 ± 2.0 × 10 −4 , P < 0.0001) and oPPS (5.3 ± 1.4 × 10 −4 , P = 0.0013) had greater nuclei density (nuclei/μm 2 ) than peripheral sclera (2.5 ± 0.8 × 10 −4 ). The iPPS (2.0 ± 0.3, P = 0.002) but not oPPS (2.4 ± 0.4, P = 0.45) nuclei had smaller aspect ratios than peripheral (2.7 ± 0.5) nuclei. FA was present throughout the scleral stroma and was more aligned with oPPS collagen (9.6 ± 1.9 degrees) than in the peripheral sclera (15.9 ± 3.9 degrees, P =0.002). The αSMA fibers in the peripheral sclera were less aligned with collagen fibrils (26.4 ± 4.8 degrees) than were FA (15.9 ± 3.9 degrees, P = 0.0002). PPS fibroblasts cultured on smooth membranes shifted to an orientation perpendicular to the direction of cyclic uniaxial strain (1 Hz, 5% strain, 42.2 ± 7.1 degrees versus 62.0 ± 8.5 degrees, P < 0.0001), whereas aligned fibroblasts on patterned membranes were resistant to strain-induced reorientation (5.9 ± 1.4 degrees versus 10 ± 3.3 degrees, P = 0.21). Resistance to re-orientation was reduced by TGFβ treatment (10 ± 3.3 degrees without TGFβ1 compared to 23.1 ± 4.5 degrees with TGFβ1, P < 0.0001). CONCLUSIONS.Regions of the posterior sclera differ in cellular density and nuclear morphology. Topography alters the cellular response to mechanical strain.
Background Prevention of nosocomial coronavirus disease 2019 (COVID-19) infection for patients undergoing flap-based reconstructive surgery is crucial to providing care and maintaining operative volume and income to support plastic surgery programs. We conducted this study to (1) determine the postoperative incidence of COVID-19 among patients undergoing flap reconstruction from December 1, 2019 to November 1, 2020 and (2) compare 30-day outcomes between patients who underwent surgery before and during the early pandemic. Methods We conducted an 11-month retrospective cohort study of all patients who underwent flap reconstruction across our institution. We abstracted patient demographics, intraoperative management, COVID-19 testing history, and 30-day postoperative complications from electronic health records. Nosocomial COVID-19 infection was defined as reverse transcription polymerase chain reaction (RT-PCR) viral ribonucleic acid detection within 30 days of patients' postoperative course or during initial surgical admission. We used chi-squared tests to compare postoperative outcomes between patients who underwent surgery before (prior to March 12, 2021, when our institution admitted its first COVID-19 patient) versus during (on/after March 12, 2021) the pandemic. Results Among the 220 patients (mean [standard deviation] age = 53.8 [18.1] years; female = 54.8%) who underwent flap reconstruction, none had nosocomial COVID-19 infection. Five (2%) patients eventually tested COVID-19 positive (median time from surgery to diagnosis: 9 months, range: 1.5–11 months) with one developing partial flap loss while infected. Between patients who underwent free flap surgery before and during the pandemic, there were no significant differences in 30-day takebacks (15.6% vs. 16.6%, respectively; p > 0.999), readmissions (9.4% vs. 12.6%, respectively; p = 0.53), and surgical complications (e.g., total flap loss 1.6% vs. 2.1%, p = 0.81). Conclusion Robust precautions can ensure the safety of patients undergoing flap surgeries across an academic medical institution, even during periods of high COVID-19 admission rates. Further studies are needed to generate evidence-based guidelines that optimize infection control and flap survival for patients undergoing reconstruction.
Background Neurolysis techniques have been adapted for decompression of peripheral nerves in multiple locations, including the common peroneal nerve (CPN) at the fibular neck. The aim of this study was to conduct a systematic review and meta-analysis to summarize the clinical outcomes of neurolysis for the management of peroneal nerve palsy (PNP). Methods Preferred Reporting Systems for Systematic Reviews and Meta-Analyses guidelines were followed for this meta-analysis. Four databases were queried, and randomized clinical trials, cohort studies, case-control studies, and case series with n > 10 published in English that evaluated clinical outcomes of neurolysis for the treatment of PNP and foot drop were included. Two reviewers completed screening and data extraction. Methodological quality was evaluated using the Newcastle-Ottawa Scale. Results A total of 493 articles were identified through literature search. Title and abstract screening identified 39 studies for full-text screening. Ten articles met the inclusion criteria for qualitative analysis, and 8 had complete data for meta-analysis. Overall, there were 368 patients (370 nerves) who had neurolysis of the CPN for PNP, of which 59.2% (n = 218) were men and 40.8% (n = 150) were women. The mean age of the patients was 47.1 years (SD, 10.0 years), mean time to surgery was 9.65 months (SD, 6.3 months), and mean follow-up time was 28 months (SD, 14.0 months). The median preoperative Medical Research Council (MRC) score was 1 (IQR 0, 3), with 42.2% (n = 156) having MRC score of 0. The median postoperative MRC score was 5 (IQR 4, 5), with 53.9% (n = 199) having MRC score of 5. Complications of neurolysis of the peroneal nerve for treatment of PNP included postoperative infection (0.54%, n = 2), wound dehiscence (0.27%, n = 1), hematoma (0.54%, n = 2), bleeding (0.27%, n = 1), relapse of PNP (0.27%, n = 1), and 1 case of mortality due to sepsis. Conclusions Our meta-analysis shows that neurolysis of the CPN is safe and improves ankle dorsiflexion strength in patients with PNP. Future studies should use a standardized method of measuring sensory outcomes, and studies of higher levels of evidence are needed to better assess the clinical outcomes of neurolysis for treatment of PNP.
Background Age is a poor predictor of postoperative outcomes in breast reconstruction necessitating new methods for risk-stratifying patients preoperatively. The 5-item modified frailty index (mFI-5) is a validated measure of frailty which assesses patients' global health. The purpose of this study was to compare the effectiveness of mFI-5 and age as independent predictors of 30-day postoperative complications following autologous breast reconstruction. Methods Patients who underwent autologous breast reconstruction between 2005 and 2019 were identified from the American College of Surgeons National Surgical Quality Improvement Program. Patients were stratified based on presence of major, minor, both minor and major, and no complications. Univariate and multivariate logistic regression were performed to determine the predictive power of mFI-5, age, and other preoperative risk factors for development of minor and major 30-day postoperative complications in all patients and stratified by flap type. Results A total of 25,215 patients were included: 20,366 (80.8%) had no complications, 2,009 (8.0%) had minor complications, 1,531 (6.1%) had major complications, and 1,309 (5.2%) had both minor and major complications. Multivariate regression demonstrated age was not a predictor of minor (odds ratio [OR]: 1.0, p = 0.045), major (OR: 1.0, p = 0.367), or both minor and major (OR: 1.0, p = 0.908) postoperative complications. mFI-5 was a significant predictor of minor complications for mFI-5 scores 1 (OR: 1.3, p < 0.001), 2 (OR: 1.8, p < 0.001), and 3 (OR: 2.8, p = 0.043). For major complications, mFI-5 was a significant predictor for scores 1 (OR: 1.2, p = 0.011) and 2 (OR: 1.3, p = 0.03). Conclusion Compared with age, mFI-5 scores were better predictors of 30-day postoperative complications following autologous breast reconstruction regardless of flap type. Additionally, higher mFI-5 scores were associated with increased odds of minor and major complications. Our findings indicate that reconstructive breast surgeons should consider using the mFI-5 in lieu of age to risk-stratify patients prior to autologous breast reconstruction surgery.
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