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Background: This study explored the surgical management and reconstruction options for augmented breasts in the context of breast conservation therapy (BCT) for breast cancer. The authors hypothesized that there would be no difference in the rates of complications, revisions, or patient satisfaction in patients who maintained their breast augmentation versus those who had their implants removed in the context of BCT., Methods: The authors conducted a retrospective review of 142 patients who underwent BCT at a single center from March of 2016 to March of 2022. The study included patients who had a preexistent cosmetic augmentation at the time of breast cancer diagnosis and BCT. Patient demographics, clinical and treatment characteristics, breast implant details, reconstructive technique, complications, and revisions were recorded. Patient-reported outcomes were assessed using the BREAST-Q BCT module., Results: Ninety-three patients (65.5%) chose to maintain their implants, whereas 49 (34.5%) elected to have them removed during BCT. Patients with submuscular implants were more likely to maintain their implants. Oncoplastic mastopexy was associated with higher complication rates, particularly in patients opting for implant downsizing. However, multivariate logistic regression did not identify implant management strategy as an independent predictor for complications or revisions. Surgical-site infection was the only predictor of implant explantation. Patient-reported outcomes did not differ significantly between the different implant management cohorts., Conclusions: This study demonstrates that maintaining breast implants during BCT does not increase the risk of complications or revisions. Overall, BCT in augmented women was found to be a safe approach, with high patient satisfaction., Clinical Question/level of Evidence: Risk, III., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background:  In appropriately selected patients, it may be possible to fully bury breast free flaps deep to the mastectomy skin flaps. Because this practice forgoes the incorporation of a monitoring skin paddle for the flap, and thus limits the ability for physical exam, it may be associated with an increased risk of flap loss or other perfusion-related complications, such as fat necrosis. We hypothesized that fully de-epithelialized breast free flaps were not associated with an increased complication rate and reduced the need for future revision surgery., Methods:  A single-institution retrospective review of 206 deep inferior epigastric artery (DIEP) flaps in 142 patients was performed between June 2016 and September 2021. Flaps were grouped into buried or nonburied categories based on the absence or presence of a monitoring paddle. Patient-reported outcomes were assessed postoperatively using the BREAST-Q breast reconstruction module. Electronic medical record data included demographics, comorbidities, flap characteristics, complications, and revision surgery., Results:  The buried flap patients ( N  = 46) had a lower median body mass index (26.9 vs 30.3, p  = 0.04) and a lower rate of hypertension (19.5 vs. 37.5%, p  = 0.04) compared with nonburied flap patients ( N  = 160). Burying flaps was more likely to be adopted in skin-sparing mastectomy or nipple-sparing mastectomy ( p  = 0.001) and in an immediate or a delayed-immediate fashion ( p  = 0.009). There was one flap loss in the nonburied group; complication rates were similar. There was a significantly greater revision rate in the nonburied flap patients (92 vs. 70%; p  = 0.002). Buried flap patients exhibited a greater satisfaction with breasts (84.5 ± 13.4 vs. 73.9 ± 21.4; p  = 0.04) and sexual satisfaction (73.1 ± 22.4 vs. 53.7 ± 29.7; p  = 0.01) compared with nonburied flap patients., Conclusion:  Burying breast free flaps in appropriately selected patients does not appear to have a higher complication rate when compared with flaps with an externalized monitoring paddle. Furthermore, this modification may be associated with a better immediate aesthetic outcome and improved patient satisfaction, as evidenced by a lower rate of revision surgery and superior BREAST-Q scores among buried DIEP flaps., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Doctor of Philosophy (PhD) is the highest academic degree awarded by universities in most fields of study. In surgery, it is thought to provide surgeons with skills to conduct high-quality research and advance academically. However, this presumed effect has not been assessed among academic plastic surgeons (APSs) and plastic surgery residents (PSRs). The purpose of this study is to determine the differences in multiple strata of career progression and success between PhD and non-PhD graduates in academic plastic surgery., Methods: We conducted a nationwide cross-sectional study of APSs and PSRs. Departmental websites of integrated plastic surgery residency programs were used to identify our study population and their demographics, degrees, and tenure status. Data on research productivity were collected using Scopus. Information on research funding was gathered through the National Institutes of Health and Plastic Surgery Foundation. To assess the plastic surgery programs' reputations, we divided residency programs into four quartiles (Q1, 1-20; Q2, 21-40; Q3, 41-60; Q4, 61+) according to their Doximity ranking., Results: We identified 841 APSs (78.5% men) and 948 PSRs (58.1% men), of whom 5.1% and 2.7% had a PhD degree, respectively. PhD graduates had significantly more advanced research portfolios. PhD APSs were more likely to secure research funding, and PhD PSRs were more likely to train at highly reputed programs. However, academic rank and leadership appointments were not significantly influenced by PhDs., Conclusion: Holding a PhD can strongly advance a plastic surgeon's research portfolio, but it does not guarantee a better position or tenure status., Level of Evidence Iii: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and International Society of Aesthetic Plastic Surgery.)

During field surveys and culture procedures, large growth disparities in Anguilla japonica have been observed. However, the potential causes are unknown. This study explored differences in digestive ability, metabolic levels, and transcriptomic profiles of appetite-related genes between growth-retarded eel (GRE) and normal-growing eel (NGE) under the same rearing conditions. The results showed that growth hormone ( gh ) mRNA expression in GREs was considerably lower than NGEs. The levels of total protein (TP), total cholesterol (T-CHO), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), blood ammonia (BA), blood urea nitrogen (BUN), and alkaline phosphatase (ALP) in GREs were significantly lower than in NGEs. Conversely, levels of glucose (GLU), alanine aminotransferase (ALT), and aspartate transaminase (AST) were higher in GREs. The activities of SOD, CAT, and T-AOC levels were also significantly lower in GREs, as were the activities of glucose-related enzymes including hexokinase (HK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G6PASE). Additionally, orexigenic genes ( npy and ghrelin ) were dramatically downregulated, whereas anorexigenic genes ( crh and pyy ) were significantly upregulated in GREs. These findings suggested that variances in growth hormone, metabolic activities, and appetite level could be associated with the different growth rates of A. japonica . The present research not only revealed the characteristics of the growth, metabolism, and appetite of GREs but also offered new perspectives into the substantial growth discrepancies in A. japonica , providing novel ideas for enhancing fish growth.

β-l-5-(( E )-2-Bromovinyl)-1-((2 S ,4 S )-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil (l-BHDU, 17 ) is a potent and selective inhibitor of the varicella-zoster virus (VZV). l-BHDU ( 17 ) has demonstrated excellent anti -VZV activity and is a preclinical candidate to treat chickenpox, shingles (herpes zoster), and herpes simplex virus 1 (HSV-1) infections. Its monophosphate prodrug (POM-l-BHDU-MP, 24 ) demonstrated an enhanced pharmacokinetic and antiviral profile. POM-l-BHDU-MP ( 24 ), in vivo , effectively reduced the VZV viral load and was effective for the topical treatment of VZV and HSV-1 infections. Therefore, a viable synthetic procedure for developing POM-l-BHDU-MP ( 24 ) is needed. In this article, an efficient approach for the synthesis of l-BHDU ( 17 ) from a readily available starting material is described in 7 steps. An efficient and practical methodology for both chiral pure l- & d-dioxolane 11 and 13 were developed via diastereomeric chiral amine salt formation. Neutralization of the amine carboxylate salt of l-dioxolane 10 provides enantiomerically pure l-dioxane 11 (ee ≥ 99%). Optically pure 11 was utilized to construct the final nucleoside l-BHDU ( 17 ) and its monophosphate ester prodrug (POM-l-BHDU-MP, 24 ). Notably, the reported process eliminates expensive chiral chromatography for the synthesis of chiral pure l- & d-dioxolane, which offers avenues for the development and structure-activity relationship studies of l- & d-dioxolane-derived nucleosides.

The FDA has approved several drugs based on the fluorinated nucleoside pharmacophore, and numerous drugs are currently in clinical trials. Fluorine-containing nucleos(t)ides offer significant antiviral and anticancer activity. The insertion of a fluorine atom, either in the base or sugar of nucleos(t)ides, alters its electronic and steric parameters and transforms the lipophilicity, pharmacodynamic, and pharmacokinetic properties of these moieties. The fluorine atom restricts the oxidative metabolism of drugs and provides enzymatic metabolic stability towards the glycosidic bond of the nucleos(t)ide. The incorporation of fluorine also demonstrates additional hydrogen bonding interactions in receptors with enhanced biological profiles. The present article discusses the synthetic methodology and antiviral activities of FDA-approved drugs and ongoing fluoro-containing nucleos(t)ide drug candidates in clinical trials.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR)., Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR., Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible., Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI., Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis., Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis., Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678)., Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

Background: Health care avoidance in the COVID-19 pandemic has been widely reported. Yet few studies have investigated the dynamics of hospital avoidance behavior during pandemic waves and inferred its impact on excess non-COVID-19 deaths., Objective: This study aimed to measure the impact of hospital avoidance on excess non-COVID-19 deaths in public hospitals in Hong Kong., Methods: This was a retrospective cohort study involving 11,966,786 patients examined between January 1, 2016, and December 31, 2021, in Hong Kong. All data were linked to service, treatment, and outcomes. To estimate excess mortality, the 2-stage least squares method was used with daily tallies of emergency department (ED) visits and 28-day mortality. Records for older people were categorized by long-term care (LTC) home status, and comorbidities were used to explain the demographic and clinical attributes of excess 28-day mortality. The primary outcome was actual excess death in 2020 and 2021. The 2-stage least squares method was used to estimate the daily excess 28-day mortality by daily reduced visits., Results: Compared with the prepandemic (2016-2019) average, there was a reduction in total ED visits in 2020 of 25.4% (548,116/2,142,609). During the same period, the 28-day mortality of non-COVID-19 ED deaths increased by 7.82% (2689/34,370) compared with 2016-2019. The actual excess deaths in 2020 and 2021 were 3143 and 4013, respectively. The estimated total excess non-COVID-19 28-day deaths among older people in 2020 to 2021 were 1958 (95% CI 1100-2820; no time lag). Deaths on arrival (DOAs) or deaths before arrival (DBAs) increased by 33.6% (1457/4336) in 2020, while non-DOA/DBAs increased only by a moderate 4.97% (1202/24,204). In both types of deaths, the increases were higher during wave periods than in nonwave periods. Moreover, non-LTC patients saw a greater reduction in ED visits than LTC patients across all waves, by more than 10% (non-LTC: 93,896/363,879, 25.8%; LTC: 7,956/67,090, 11.9%). Most of the comorbidity subsets demonstrated an annualized reduction in visits in 2020. Renal diseases and severe liver diseases saw notable increases in deaths., Conclusions: We demonstrated a statistical method to estimate hospital avoidance behavior during a pandemic and quantified the consequent excess 28-day mortality with a focus on older people, who had high frequencies of ED visits and deaths. This study serves as an informed alert and possible investigational guideline for health care professionals for hospital avoidance behavior and its consequences., (©Abraham Ka-chung Wai, Tsz Fung Yip, Yui Hang Wong, Chun Kit Chu, Teddy Lee, Ken Hung On Yu, Wang Leong So, Janet Y H Wong, Carlos King-ho Wong, Joshua W Ho, Timothy Rainer. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 13.02.2024.)

Hydrogels composed of naturally-derived biopolymers have garnered significant research interest due to the bioavailability and biocompatibility of starting materials. However, translating these advantages to practical use is challenged by limitations of mechanical properties and stability of the resulting materials. The development of double network (DN) hydrogels has led to greatly enhanced mechanical properties and shows promise toward broadening the applications of conventional synthetic or natural hydrogels. This review highlights recently developed protein-based and polysaccharide-based DN hydrogels. For each biopolymer, we focus on a subset of DN hydrogels centered around a theme related to synthetic design or applications. Network structures and crosslinking mechanisms that endow enhanced mechanical properties and performance to the materials are discussed. Important applications, including tissue engineering, drug delivery, bioadhesives, wound healing, and wearable sensors, that arise from the inherent properties of the natural polymer or its combination with other materials are also emphasized. Finally, we discuss ongoing challenges to stimulate the discovery of new design principles for the future of DN hydrogels based on naturally-derived polymers for biological applications.

Summary: Thigh-based flaps are increasingly popular options for autologous breast reconstruction in the setting of abdominal donor-site inadequacy, previous surgery, or patient preference, but the volume and skin associated with these flaps are often lacking relative to the abdomen. An individualized, shared decision-making approach to donor-site selection was adopted based on body shape, surgical history, lifestyle, reconstructive needs, and patient expectations. Different thigh-based flaps combined in stacked, bipedicled, or conjoined configurations were selected to maximize efficient use of available soft-tissue skin and volume while optimizing donor-site aesthetics. A total of 23 thigh-based stacked, bipedicled, or conjoined profunda artery perforator (PAP), lateral thigh perforator (LTP), or gracilis musculocutaneous flap components were used in six patients. Configurations included bilateral stacked PAP and LTP flaps, bipedicled posterolateral thigh flaps based on the LTP and PAP (L-PAP), and bipedicled thigh flaps based on the gracilis and PAP pedicles. Most anastomoses were performed to the antegrade and retrograde internal mammary vessels; intraflap anastomoses were performed in one case. There were no partial or total flap losses. There was one donor-site seroma. Design of stacked, bipedicled, and conjoined thigh-based flaps using multiple conventional flap components allows for tailored approaches to donor-site utilization based on individual body shape in selected patients. Bipedicled design with the L-PAP flap represents one strategy in appropriate cases to overcome skin and volume deficiencies while facilitating coning and projection., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: Skin-preserving, staged, microvascular, breast reconstruction often is preferred in patients requiring postmastectomy radiotherapy (PMRT) but may lead to complications. We compared the long-term surgical and patient-reported outcomes between skin-preserving and delayed microvascular breast reconstruction with and without PMRT., Methods: We conducted a retrospective, cohort study of consecutive patients who underwent mastectomy and microvascular breast reconstruction between January 2016 and April 2022. The primary outcome was any flap-related complication. The secondary outcomes were patient-reported outcomes and tissue-expander complications., Results: We identified 1002 reconstructions (672 delayed; 330 skin-preserving) in 812 patients. Mean follow-up was 24.2 ± 19.3 months. PMRT was required in 564 reconstructions (56.3%). In the non-PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (β - 0.32, p = 0.045) and lower odds of 30-days readmission (odds ratio [OR] 0.44, p = 0.042), seroma (OR 0.42, p = 0.036), and hematoma (OR 0.24, p = 0.011) compared with delayed reconstruction. In the PMRT group, skin-preserving reconstruction was independently associated with shorter hospital stay (β - 1.15, p < 0.001) and operative time (β - 97.0, p < 0.001) and lower odds of 30-days readmission (OR 0.29, p = 0.005) and infection (OR 0.33, p = 0.023) compared with delayed reconstruction. Skin-preserving reconstruction had a 10.6% tissue expander loss rate and did not differ from delayed reconstruction in terms of patient-reported satisfaction with breast, psychosocial well-being, or sexual well-being., Conclusions: Skin-preserving, staged, microvascular, breast reconstruction is safe regardless of the need for PMRT, with an acceptable tissue expander loss rate, and is associated with improved flap outcomes and similar patient-reported quality of life to that of delayed reconstruction., (© 2023. Society of Surgical Oncology.)

Introduction: The lateral forearm flap (LFF) is a thin fasciocutaneous flap with a donor site that can be closed primarily., Methods: A retrospective analysis of donor site morbidity and hand function was performed in patients who underwent a radial forearm flap (RFF), ulnar artery perforator flap (UAPF), or LFF. Flap thickness was evaluated radiographically in 50 control patients., Results: Of 134 patients (lateral forearm flap: n = 49, RFF: n = 47, UAPF: n = 38), the LFF demonstrated significantly faster return to baseline hand grip strength (3 months vs. 12 months in RFF and UAPF; p < 0.001), had significantly fewer donor site complications (6.1% compared to 6.4% in RFF and 28.9% in UAPF; p = 0.003) and fewer sensory deficits (2.0% compared to 6.4% in RFF and 15.8% in UAPF sites; p = 0.013). The radiographic study confirmed the LFF to be the thinnest of all upper extremity flap options., Conclusions: The LFF is an excellent forearm-based flap option with thin, pliable tissue and low donor site morbidity., (© 2023 Wiley Periodicals LLC.)

Background: Although obesity has previously been associated with poor outcomes after mastectomy and breast reconstruction, its impact across the WHO obesity classification spectrum and the differential effects of various optimization strategies on patient outcomes have yet to be delineated. We sought to examine the impact of WHO obesity classification on intraoperative surgical and medical complications, postoperative surgical and patient-reported outcomes of mastectomy and autologous breast reconstruction, and delineate outcomes optimization strategies for obese patients., Study Design: This is a review of consecutive patients who underwent mastectomy and autologous breast reconstruction from 2016 to 2022. Primary outcomes were complication rates. Secondary outcomes were patient-reported outcomes and optimal management strategies., Results: We identified 1,640 mastectomies and reconstructions in 1,240 patients with mean follow-up of 24.2 ± 19.2 months. Patients with class II/III obesity had higher adjusted risk of wound dehiscence (odds ratio [OR] 3.20; p < 0.001), skin flap necrosis (OR 2.60; p < 0.001), deep venous thrombosis (OR 3.90; p < 0.033), and pulmonary embolism (OR 15.3; p = 0.001) than nonobese patients. Obese patients demonstrated significantly lower satisfaction with breasts (67.3 ± 27.7 vs 73.7 ± 24.0; p = 0.043) and psychological well-being (72.4 ± 27.0 vs 82.0 ± 20.8; p = 0.001) than nonobese patients. Unilateral delayed reconstructions were associated with independently shorter hospital stay (β -0.65; p = 0.002) and lower adjusted risk of 30-day readmission (OR 0.45; p = 0.031), skin flap necrosis (OR 0.14; p = 0.031), and pulmonary embolism (OR 0.07; p = 0.021)., Conclusions: Obese women should be closely monitored for adverse events and lower quality of life, offered measures to optimize thromboembolic prophylaxis, and advised on the risks and benefits of unilateral delayed reconstruction., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Patient-level characteristics associated with the prevalence and severity of financial anxiety have yet to be described. We conducted a cross-sectional analysis of survey data assessing financial anxiety in patients with chronic medical conditions in December 2020. 1771 patients (42.6% response rate) participated in the survey. Younger age (19-35 age compared to ≥ 75 age) (β, 5.86; 95% CI 2.10-9.63), male sex (β, - 1.9; 95% CI - 3.1 to - 0.73), Hispanic/Latino race/ethnicity (compared with White patients) (β, 2.55; 95% CI 0.39-4.71), household size ≥ 4 (compare with single household) (β, 4.54; 95% CI 2.44-6.64), household income of ≥ $96,000-$119,999 (compared with ≤ $23,999) (β, - 3.2; 95% CI - 6.3 to 0.04), single marital status (compared with married) (β, 2.18; 95% CI 0.65-3.71), unemployment (β, 2.07; 95% CI 0.39-3.74), high-school education (compared with advanced degrees) (β, 3.10; 95% CI 1.32-4.89), lack of insurance coverage (compared with private insurance) (β, 6.05; 95% CI 2.66-9.45), more comorbidities (≥ 3 comorbidities compared to none) (β, 2.95; 95% CI 1.00-4.90) were all independently associated with financial anxiety. Patients who are young, female, unmarried, and representing vulnerable sub-populations are at elevated risk for financial anxiety., (© 2023. The Author(s).)

Background:  Following implant-based breast reconstruction (IBR) infection and explantation, autologous reconstruction is a common option for patients who desire further reconstruction. However, few data exist about the outcomes of secondary autologous reconstruction (i.e., free flap breast reconstruction) in this population. We hypothesized that autologous reconstruction following infected device explantation is safe and has comparable surgical outcomes to delayed-immediate reconstruction., Methods:  We conducted a retrospective analysis of patients who underwent IBR explantation due to infection from 2006 through 2019, followed by secondary autologous reconstruction. The control cohort comprised patients who underwent planned primary delayed-immediate reconstruction (tissue expander followed by autologous flap) in 2018., Results:  We identified 38 secondary autologous reconstructions after failed primary IBR and 52 primary delayed-immediate reconstructions. Between secondary autologous and delayed-immediate reconstructions, there were no significant differences in overall complications (29 and 37%, respectively, p  = 0.45), any breast-related complications (18 and 21%, respectively, p  = 0.75), or any major breast-related complications (13 and10%, respectively, p  = 0.74). Two flap losses were identified in the secondary autologous reconstruction group while no flap losses were reported in the delayed-immediate reconstruction group ( p  = 0.18)., Conclusion:  Autologous reconstruction is a reasonable and safe option for patients who require explantation of an infected prosthetic device. Failure of primary IBR did not confer significantly higher risk of complications after secondary autologous flap reconstruction compared with primary delayed-immediate reconstruction. This information can help plastic surgeons with shared decision-making and counseling for patients who desire reconstruction after infected device removal., Competing Interests: None declared., (Thieme. All rights reserved.)

Varicella zoster virus (VZV) establishes lifelong infection after primary disease and can reactivate. Several drugs are approved to treat VZV diseases, but new antivirals with greater potency are needed. Previously, we identified β-l-5-(( E) -2-bromovinyl)-1-((2 S ,4 S )-2-(hydroxymethyl)-1,3-(dioxolane-4-yl))uracil (l-BHDU, 1 ), which had significant anti-VZV activity. In this communication, we report the synthesis and evaluation of numerous l-BHDU prodrugs: amino acid esters ( 14 - 26 ), phosphoramidates ( 33 - 34 ), long-chain lipids (ODE-l-BHDU-MP, 38 , and HDP-l-BHDU-MP, 39 ), and phosphate ester prodrugs (POM-l-BHDU-MP, 41 , and POC-l-BHDU-MP, 47 ). The amino acid ester l-BHDU prodrugs (l-phenylalanine, 16 , and l-valine, 17 ) had a potent antiviral activity with EC 50 values of 0.028 and 0.030 μM, respectively. The phosphate ester prodrugs POM-l-BHDU-MP and POC-l-BHDU-MP had a significant anti-VZV activity with EC 50 values of 0.035 and 0.034 μM, respectively, and no cellular toxicity (CC 50 > 100 μM) was detected. Out of these prodrugs, ODE-l-BHDU-MP ( 38 ) and POM-l-BHDU-MP ( 41 ) were selected for further evaluation in future studies.

Cadmium (Cd 2+ ) exposure induces chronic kidney disease and renal cancers, which originate from injury and cancerization of renal tubular cells. Previous studies have shown that Cd 2+ induced cytotoxicity by disrupting the intracellular Ca 2+ homeostasis that is physically regulated by the endoplasmic reticulum (ER) Ca 2+ store. However, the molecular mechanism of ER Ca 2+ homeostasis in Cd 2+ -induced nephrotoxicity remains unclear. In this study, our results firstly revealed that the activation of calcium-sensing receptor (CaSR) by NPS R-467 could protect against Cd 2+ exposure-induced cytotoxicity of mouse renal tubular cells (mRTEC) by restoring ER Ca 2+ homeostasis through the ER Ca 2+ reuptake channel sarco/endoplasmic reticulum Ca 2+ -ATPase (SERCA). Cd 2+ -induced ER stress and cell apoptosis were effectively abrogated by SERCA agonist CDN1163 and SERCA2 overexpression. In addition, in vivo, and in vitro results proved that Cd 2+ reduced the expressions of SERCA2 and its activity regulator phosphorylation phospholamban (p-PLB) in renal tubular cells. Cd 2+ -induced SERCA2 degradation was suppressed by the treatment of proteasome inhibitor MG132, which suggested that Cd 2+ reduced SERCA2 protein stability by promoting the proteasomal protein degradation pathway. These results suggested that SERCA2 played pivotal roles in Cd 2+ -induced ER Ca 2+ imbalance and stress to contribute to apoptosis of renal tubular cells, and the proteasomal pathway was involved in regulating SERCA2 stability. Our results proposed a new therapeutic approach targeting SERCA2 and associated proteasome that might protect against Cd 2+ -induced cytotoxicity and renal injury.

Introduction: Lymphedema surgery including lymphovenous anastomosis (LVA) and vascularized lymph node transfer (VLNT) are effective treatments for lymphedema; however, treating multiple limbs in a single operation using both approaches has not been described. We hypothesize multiple limb lymphedema can be treated effectively in one operation., Patient and Methods: Retrospective review of seven patients undergoing extreme lymphedema surgery (mean age: 53.2 years; range: 33-66 years) with an average BMI of 34.8 kg/m 2 (range: 17.6-53.6 kg/m 2 ). Two patients developed bilateral upper extremity (UE) lymphedema secondary to breast cancer treatment, three had bilateral lower extremity (LE) lymphedema, and two suffered from lymphedema of all four extremities due to breast cancer treatment., Results: One patient with bilateral UE lymphedema was treated with bilateral inguinal node transfers with LVA and the other with combined bilateral DIEP flaps and inguinal node transfers with LVA. Three patients had bilateral LE lymphedema: two were treated with split omental/gastroepiploic nodes, and one underwent simultaneous supraclavicular and submental node transfers. LVAs were performed in one leg in each patient. Two patients with four-limb lymphedema underwent bilateral inguinal node transfers with DIEP flaps and bilateral LE LVA. In total, there were eight UE and 10 LE treated. Average follow-up was 15.8 months (range: 12.6-28.4 months), all patients reported subjective improvement in symptoms, were able to decrease use of compression garments and pumps, and no patients developed cellulitis., Conclusion: Patients suffering from lymphedema of multiple extremities can be treated safely and effectively combining both LVA and VLNT in a single operation., (© 2022 Wiley Periodicals LLC.)

Background: Neighborhood-level factors have been shown to influence surgical outcomes through material deprivation, psychosocial mechanisms, health behaviors, and access to resources. To date, no study has examined the relationship between area-level deprivation (ADI) and post-mastectomy outcomes., Methods: A cross-sectional survey of adult female breast cancer patients who underwent lumpectomy or mastectomy between January 2018 to June 2019 was carried out. Patient-specific characteristics and ADI information were abstracted and correlated with postoperative global- (SF-12) and condition-specific (BREAST-Q) quality-of-life performance via multivariable regression. Patients were classified into three ADI terciles: 0-39 (low deprivation), 40-59 (moderate deprivation), and 60-100 (high deprivation)., Results: A total of 564 consecutive patients were identified, being mostly white (75%) with mean age of 60.2 ± 12.4 years, median body mass index of 27.8 [interquartile range (IQR) 24.3-32.2) kg/m 2 , median Charlson Comorbidity Index of 3 (IQR 2-5), and mean ADI of 42.3 ± 25.7. African American and Hispanic patients and those with high BMI were more likely to reside in highly deprived neighborhoods (p = 0.003 and p < 0.001). In adjusted models, patients in highly deprived neighborhoods had significantly lower mean SF-12 physical (44.9 [95% CI, 43.8-46.0] versus 44.9 [95% CI, 43.7-46.1] versus 46.3 [95% CI, 45.3-47.3], p = 0.03) and BREAST-Q psychosocial well-being scores (63.5 [95% CI, 59.32-67.8] versus 69.3 [95% CI, 65.1-73.6] versus 69.7 [95% CI, 66.4-73.1], p = 0.01) relative to moderate- and low-deprivation groups., Conclusions: Patients residing in the most deprived neighborhoods were identified to have worse psychological well-being and quality-of-life. The ADI should be incorporated into the shared decision-making process and perioperative counseling to engender value-based and personalized care, especially for vulnerable populations., (© 2022. Society of Surgical Oncology.)

Japanese eels (Anguilla japonica) are commercially important species, harvested extensively for food. Currently, this and related species (American and European eels) are challenging to breed on a commercial basis. As a result, the wild stock is used for aquaculture. Moreover, climate change, habitat loss, water pollution, and altered ocean currents affect eel populations negatively. Accordingly, the International Union for Conservation of Nature lists Japanese eels as endangered and on its red list. Here we presented a high-quality genome assembly for Japanese eels and demonstrated that large chromosome reorganizations occurred in the events of third-round whole-genome duplications (3R-WRDs). Several chromosomal fusions and fissions have reduced the ancestral protochromosomal number of 25 to 19 in the Anguilla lineage. A phylogenetic analysis of the expanded gene families showed that the olfactory receptors (group δ and ζ genes) and voltage-gated Ca2+ channels expanded significantly. Both gene families are crucial for olfaction and neurophysiology. Additional tandem and proximal duplications occurred following 3R-WGD to acquire immune-related genes for an adaptive advantage against various pathogens. The Japanese eel assembly presented here can be used to study other Anguilla species relating to evolution and conservation., (© The Author(s) 2022. Published by Oxford University Press GigaScience.)

We examined the changes in hepatic metabolic gene expression and gut microbiota of offspring exposed to PFOS in-utero. At GD17.5, our data showed that PFOS exposure decreased fetal bodyweights and hepatic metabolic gene expressions but increased relative liver mass and lipid accumulation. At PND21, in-utero high-dose PFOS-exposed offspring exhibited significantly greater bodyweight (catch-up-growth), associated with significant induction of hepatic metabolic gene expression. In addition, 16SrRNA-sequencing of the cecal samples revealed an increase in carbohydrate catabolism but a reduction in microbial polysaccharide synthesis and short-chain fatty acid (SCFA) metabolism. From PND21-80, a postnatal diet-challenge for the offspring was conducted. At PND80 under a normal diet, in-utero high-dose PFOS-exposed offspring maintained the growth "catch-up" effect. In contrast, in a high-fat-diet, the bodyweight of in-utero high-dose PFOS-exposed adult offspring were significantly lesser than the corresponding low-dose and control groups. Even though in the high-fat-diet, the in-utero PFOS-exposed adult offspring showed significant upregulation of hepatic metabolic genes, the lower bodyweight suggests that they had difficulty utilizing high-fat nutrients. Noteworthy, the metagenomic data showed a significant reduction in the biosynthesis of microbial polysaccharides, vitamin B, and SCFAs in the PFOS-exposed adult offspring. Furthermore, the observed effects were significantly reduced in the PFOS-exposed adult offspring with the high-fat diet but supplemented with sucrose. Our study demonstrated that in-utero PFOS exposure caused inefficient fat metabolism and increased the risk of hepatic steatosis in offspring., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Summary: An aesthetically pleasing umbilicus is a critical component to the overall cosmesis and resultant patient satisfaction after deep inferior epigastric artery perforator (DIEP) flap breast reconstruction. Because of variables in body habitus, comorbidities, and technical aspects of the procedure, patients undergoing DIEP flap breast reconstruction are at a higher risk of umbilical complications and poor aesthetic appearance of the neoumbilicus compared with those undergoing cosmetic abdominoplasty. To minimize these potential problems and maximize the overall aesthetic appearance of the abdomen, the authors propose an algorithmic approach to umbilical inset after DIEP flap harvest that takes into account several critical factors: the thickness of the subcutaneous tissue of the abdominal flap, the length of the umbilical stalk, and the depth of the umbilical bowl. This simple algorithmic approach is a useful tool that will assist surgeons in minimizing umbilical complications and delivering a superior cosmetic appearance to the abdominal donor site in DIEP flap reconstruction., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: As more plastic surgery clinicians pursue advanced degrees and strive to become stronger physician-scientists, an objective understanding of how such degrees influence careers becomes important. We hypothesized that having a master's degree is associated with higher scholarly activity, research funding, academic progression, and leadership appointments., Methods: Accreditation Council for Graduate Medical Education-accredited integrated plastic surgery residency program Web sites were queried to create a data set of current academic plastic surgeons (APSs) and plastic surgery residents (PSRs). Scholarly metrics such as publications, citations, and H-indices were extracted from the Scopus database. National Institutes of Health and Plastic Surgery Foundation funding information was collected through their respective Web sites., Results: Our cohort comprised 799 APSs and 922 PSRs, of whom 8% and 7.4%, respectively, had at least one master's degree. Academic plastic surgeons with master's of public health degrees had a significantly higher median number of publications and citations than APSs without a master's of public health. There was no association between any master's degree and academic rank or being a department chairman or program director. Academic plastic surgeons with master of science degrees were more likely to receive National Institutes of Health grants. Among PSRs, master's of science graduates had a higher median number of publications. Other master's degrees did not significantly influence scholarly productivity or funding., Conclusions: Certain master's degrees had an impact on scholarly productivity, with no significant effect on academic rank or leadership positions. The value of master's degrees in programs focusing on healthcare management, leadership skills, and business acumen likely extends beyond the scope of this study., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Telemedicine use during the COVID-19 pandemic among financially distressed patients with cancer, with respect to the determinants of adoption and patterns of utilization, has yet to be delineated. We sought to systematically characterize telemedicine utilization in financially distressed patients with cancer during the COVID-19 pandemic., Methods: We conducted a cross-sectional analysis of nationwide survey data assessing telemedicine use in patients with cancer during the COVID-19 pandemic collected by Patient Advocate Foundation (PAF) in December 2020. Patients were characterized as financially distressed by self-reporting limited financial resources to manage out-of-pocket costs, psychological distress, and/or adaptive coping behaviors. Primary study outcome was telemedicine utilization during the pandemic. Secondary outcomes were telemedicine utilization volume and modality preferences. Multivariable and Poisson regression analyses were used to identify factors associated with telemedicine use., Results: A convenience sample of 627 patients with cancer responded to the PAF survey. Telemedicine adoption during the pandemic was reported by 67% of patients, with most (63%) preferring video visits. Younger age (19-35 age compared to ≥ 75 age) (OR, 6.07; 95% CI, 1.47-25.1) and more comorbidities (≥ 3 comorbidities compared to cancer only) (OR, 1.79; 95% CI, 1.13-2.65) were factors associated with telemedicine adoption. Younger age (19-35 years) (incidence rate ratios [IRR], 1.78; 95% CI, 24-115%) and higher comorbidities (≥ 3) (IRR; 1.36; 95% CI, 20-55%) were factors associated with higher utilization volume. As area deprivation index increased by 10 units, the number of visits decreased by 3% (IRR 1.03, 95% CI, 1.03-1.05)., Conclusions: The rapid adoption of telemedicine may exacerbate existing inequities, particularly among vulnerable financially distressed patients with cancer. Policy-level interventions are needed for the equitable and efficient provision of this service., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The goal of this study was to assess whether adding a latissimus dorsi (LD) flap to a secondary implant-based reconstruction (IBR) improves outcomes following explantation of the primary device due to infection., Methods: We conducted a retrospective study of patients who underwent a second IBR with or without the addition of an LD flap during 2006-2019, following explantation due to infection. Surgical outcomes were collected and compared between reconstruction types., Results: A total of 6093 IBRs were identified during the study period. Of these, 109 underwent a second attempt at breast reconstruction with IBR alone (n = 86, 79%) or IBR/LD (n = 23, 21%) following explantation of an infected device. Rates of secondary device explantation due to a complication were similar between the two groups (26% in the IBR/LD group and 21% in the IBR group; P = 0.60). Among the patients who underwent prior radiotherapy, the IBR/LD group had lower rates of any complication (38% versus 56%; P = 0.43), infection (25% versus 44%; P = 0.39), and reconstruction failure (25% versus 44%; P = 0.39); however, differences were not statistically significant., Conclusion: Following a failed primary breast reconstruction due to infection, it may be appropriate to offer a secondary reconstruction. For patients with a history of radiotherapy, combining an LD flap with IBR may provide benefits over IBR alone. Although not statistically different, this outcome may have clinical significance, considering the magnitude of the effect, and may result in decreased complication rates and a higher chance of reconstructive success., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Infection is a dreaded complication of implant-based breast reconstruction. There is a paucity of literature on the outcomes of a secondary reconstruction after infected implant-based breast reconstruction explantation., Methods: The authors conducted a retrospective study of patients who underwent a second implant-based breast reconstruction following a failed infected device between January of 2006 and December of 2019. Surgical and patient-reported outcomes (BREAST-Q) were collected and analyzed., Results: A total of 6093 implant-based breast reconstructions were performed during the study period, 298 (5 percent) of which involved device removal because of infection. Eighty-three patients ultimately received 92 second-attempt breast implants. Thirty-six percent of cases developed at least one postoperative complication, with infection [23 breasts (25 percent)] being the most common. Compared with first-attempt implant-based breast reconstruction, we found significantly higher infection rates among second-attempt cases (9 percent and 21 percent, respectively; p = 0.0008). Patient-reported satisfaction with the breast and sexual well-being were lower after second-attempt than after first-attempt implant-based breast reconstruction ( p = 0.018 and p = 0.002, respectively) reported in the literature. Mean follow-up was 41 ± 35 months. If we exclude patients with prior radiation therapy and those who received device exchange, the success rate is 88 percent., Conclusions: It is reasonable to offer women second-attempt implant-based breast reconstruction after explantation because of infection. However, this patient population has a higher infection and explantation rate and lower patient-reported satisfaction than patients undergoing first-attempt implant-based breast reconstruction. Because of these increased surgical risks and elevated complication rates, patients must be given reasonable expectations during preoperative discussions and when providing informed consent for second-attempt implant-based breast reconstruction., Clinical Question/level of Evidence: Risk, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Stanniocalcin-1 (STC1) is a hypocalcemic hormone originally identified in bony fishes. The mammalian homolog is found to be involved in inflammation and carcinogenesis, among other physiological functions. In this study, we used the TriCEPS-based ligand-receptor methodology to identify the putative binding proteins of human STC1 (hSTC1) in the human leukemia monocytic cell line, ThP-1. LC-MS/MS analysis of peptides from shortlisted hSTC1-binding proteins detected 32 peptides that belong to IGF2/MPRI. Surface plasmon resonance assay demonstrated that hSTC1 binds to immobilized IGF2R/MPRI with high affinity (10-20 nM) and capacity (Rmax 70-100%). The receptor binding data are comparable with those of (CREG) cellular repressor of E1A-stimulated gene a known ligand of IGF2R/MPRI, with Rmax of 75-80% and affinity values of 1-2 nM. The surface plasmon resonance competitive assays showed CREG competed with hSTC1 in binding to IGF2R/MPRI. The biological effects of hSTC1 on ThP-1 cells were demonstrated via IGF2R/MPRI to significantly reduce secreted levels of IL-1β. This is the first study to reveal the high-affinity binding of hSTC1 to the membrane receptor IGF2R/MPRI., (© 2022 Wan et al.)

Background: Implant-based breast reconstruction infections often require implant explantation. Whereas some plastic surgeons pursue autologous reconstruction following the first implant-based breast reconstruction failure caused by infection, others argue that a second attempt is acceptable., Methods: The authors conducted a retrospective study of patients who underwent a second reconstruction attempt with implant-based or free flap breast reconstruction following explantation because of infection between 2006 and 2019. Surgical and patient-reported outcomes were compared between the two groups., Results: A total of 6093 implant-based breast reconstructions were performed during the study period, of which 130 breasts met our inclusion criteria [implant-based, n = 86 (66 percent); free flap, n = 44 (34 percent)]. No significant differences in rates of overall (25 percent versus 36 percent; p = 0.2) or major (20 percent versus 21 percent; p = 0.95) complications were identified between the free flap and implant-based cohorts, respectively. Implant-based breast reconstruction patients were more likely to experience a second infection (27 percent versus 2 percent; p = 0.0007) and reconstruction failure (21 percent versus 5 percent; p = 0.019). Among irradiated patients, reconstruction failure was reported in 44 percent of the implant-based and 7 percent of the free flap cohorts (p = 0.02). Free flap patients reported significantly higher scores for Satisfaction with Breasts (73.7 ± 20.1 versus 48.5 ± 27.9; p = 0.0046)., Conclusions: Following implant-based breast reconstruction explantation because of infection, implant-based and free flap breast reconstruction had similar rates of overall and major complications; however, implant-based breast reconstruction had considerably higher rates of infection and reconstructive failures and lower patient-reported scores for Satisfaction with Breasts. Given the high rates of implant-based breast reconstruction failure in patients with prior radiotherapy and infection-based failure, plastic surgeons should strongly consider autologous reconstruction in this patient population., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Predatory journals have exploited the open access publishing model and are considered as a major threat to the integrity of scientific research. The goal of this study was to characterize predatory publishing practices in plastic surgery., Methods: To identify potentially predatory journals in the field of plastic surgery, the authors searched the Cabells' Predatory Reports and Beall's List using preidentified keywords. For presumed legitimate open access journals, the Directory of Open Access Journals (DOAJ) was queried. The characteristics of potentially predatory journals were compared to those of legitimate open access plastic surgery journals., Results: The authors identified a total of 25 plastic surgery-focused journals. Out of the 25 potentially predatory journals, only 15 journals had articles published within the last 5 years, with a mean number of articles of 33 ± 39 (range, 2 to 159 articles). The mean number of predatory violations according to Cabells' criteria was 6.8 ± 1.4 (range, 3 to 9). Using the DOAJ database, the authors identified a total of 24 plastic surgery-related journals. Compared to potentially predatory journals, journals from the DOAJ were more likely to be indexed in PubMed (0 versus 50 percent, respectively, p < 0.0001). Time to publication was significantly higher in journals from the DOAJ (17 ± 7 versus 4 ± 1 weeks; p = 0.006). Despite higher article processing charges in the DOAJ group, this difference was not statically significant ($1425 ± $717 versus $1071 ± $1060; p = 0.13)., Conclusions: Predatory journals are pervasive in the medical literature and plastic surgery is no exception. Plastic surgeons should practice due diligence when choosing a target journal for their articles. Journals with predatory practices should be distinguished from legitimate open access publication platforms., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: Robotic surgery is emerging as a viable tool in reconstructive surgery. Harvesting of the deep inferior epigastric perforator flap is typically performed through an anterior approach, which involves a long fascial incision. A robotic approach allows the deep inferior epigastric pedicle to be harvested from the posterior surface. This approach reduces the length of the fascial incision and should decrease the abdominal morbidity associated with large fascial dissections., Methods: A case series study of 21 patients who underwent a robotic deep inferior epigastric perforator or during a 12-month period for breast reconstruction was performed. Patient demographics, surgical characteristics, and complications were assessed., Results: Mean patient age was 54.6 ± 7.6 years, and mean body mass index was 30.4 ± 3.9 kg/m2. Mean fascial incision and pedicle length were 3.6 ± 1.6 cm and 13.3 ± 1 cm, respectively. None of the patients required conversion to open harvest. Mean length of hospital stay was 3.8 ± 0.9 days. Surgical site occurrences were identified in five patients (31.3 percent). One patient had delayed wound healing at the donor site. None of the patients developed hernia or bulge. The mean benefit (B = C - A), defined as length of fascial incision spared and measured as the difference between pedicle length and intramuscular course, was 9.83 ± 2.28 cm. The precision of computed tomography angiography in identifying the intraoperative fascial incision was 86 percent., Conclusion: The robotic deep inferior epigastric perforator flap is a safe and reliable technique that decreases the length of fascial incision and short-term complications associated with the open approach., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Although abdominally-based free flaps have long been the gold standard, the profunda artery perforator (PAP) flap has emerged as an important alternative option for autologous breast reconstruction. The aim of this study was to directly compare the donor site morbidity of using the PAP versus deep inferior epigastric perforator (DIEP) free flap., Methods: We performed a retrospective review of patients undergoing autologous breast reconstruction using a DIEP and/or PAP flap from January 2017 to December 2020. In total, 30 PAP flap patients were matched with 60 DIEP flap patients. Outcomes included donor site wound dehiscence, length of stay, narcotic consumption, and pain scores. Patient-reported outcomes for the thigh versus abdomen were compared using questions derived from the BREAST-Q., Results: There was no significant difference in length of stay ( P = 0.182), reoperation rates ( P = 0.999), flap failure rates ( P = 0.999), or donor site complications ( P = 0.999). Both groups had similar mean pain scores, maximum pain scores, daily and total narcotic requirements. In comparing the thigh or abdomen as a donor site, there was no difference in frequency of negative symptoms (difficulty with daily activities, discomfort, tightness, and negative impact on ability to work) or satisfaction scores as related to their appearance in and out of clothing and the appearance of the scar., Conclusions: The thigh and abdomen are both suitable donor sites for autologous breast reconstruction with similar flap-related and patient-reported outcomes. The ultimate decision regarding whether to use a PAP or DIEP flap for breast reconstruction should be tailored based on patient anatomy and preference., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Reducing complications while controlling costs is a central tenet of value-based health care. Bilateral microvascular breast reconstruction is a long operation with a relatively high complication rate. Using a two-surgeon team has been shown to improve safety in bilateral microvascular breast reconstruction; however, its impact on cost and efficiency has not been robustly studied. The authors hypothesized that a cosurgeon for bilateral microvascular breast reconstruction is safe, effective, and associated with reduced costs., Methods: The authors retrospectively reviewed all patients who underwent bilateral microvascular breast reconstruction with either a single surgeon or surgeon/cosurgeon team over an 18-month period. Charges were converted to costs using the authors' institutional cost-to-charge ratio. Surgeon opportunity costs were estimated using time-driven activity-based costing. Propensity scoring controlled for baseline characteristics between the two groups. A locally weighted logistic regression model analyzed the cosurgeon's impact on outcomes and costs., Results: The authors included 150 bilateral microvascular breast reconstructions (60 single-surgeon and 90 surgeon/cosurgeon reconstructions) with a median follow-up of 15 months. After matching, the presence of a cosurgeon was associated with a significantly reduced mean operative duration (change in operative duration, -107 minutes; p < 0.001) and cost (change in total cost, -$1101.50; p < 0.001), which was even more pronounced when surgeon/cosurgeon teams worked together frequently (change in operative duration, -132 minutes; change in total cost, -$1389; p = 0.007). The weighted logistic regression models identified that a cosurgeon was protective against breast-site complications and trended toward reduced overall and major complication rates., Conclusion: The practice of using a of cosurgeon appears to be associated with reduced costs and improved outcomes, thereby potentially adding value to bilateral microvascular breast reconstruction., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2022 by the American Society of Plastic Surgeons.)

Background: The Open Payments Program, as designated by the Physician Payments Sunshine Act, is the single largest repository of industry payments made to licensed physicians within the United States. Though sizeable in its dataset, the database and user interface are limited in their ability to permit expansive data interpretation and summarization., Objectives: The authors sought to comprehensively compare industry payments made to plastic surgeons with payments made to all surgeons and all physicians to elucidate industry relationships since implementation., Methods: The Open Payments Database was queried between 2014 and 2019, and inclusion criteria were applied. These data were evaluated in aggregate and for yearly totals, payment type, and geographic distribution., Results: A total 61,000,728 unique payments totaling $11,815,248,549 were identified over the 6-year study period; 9089 plastic surgeons, 121,151 surgeons, and 796,260 total physicians received these payments. Plastic surgeons annually received significantly less payment than all surgeons (P = 0.0005). However, plastic surgeons did not receive significantly more payment than all physicians (P = 0.0840). Cash and cash equivalents proved to be the most common form of payment; stock and stock options were least commonly transferred. Plastic surgeons in Tennessee received the most in payments between 2014 and 2019 (mean $76,420.75). California had the greatest number of plastic surgeons who received payments (1452 surgeons)., Conclusions: Plastic surgeons received more in industry payments than the average of all physicians but received less than all surgeons. The most common payment was cash transactions. Over the past 6 years, geographic trends in industry payments have remained stable., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

The self-assembly of poly(dimethylsiloxane)- b -poly(trimethylene carbonate) (PDMS- b -PTMC) bottlebrush block polymers was investigated under different processing conditions. Small-angle X-ray scattering (SAXS) and UV/Visible spectroscopy provided insight into the self-assembly and structure in response to heating and applied pressure. In the absence of applied pressure (i.e., before annealing), the PDMS- b -PTMC bottlebrush block polymers are white solids and adopt small, randomly oriented lamellar grains. Heating the materials to 140 °C in the absence of applied pressure appears to "lock in" the isotropic, short-range-ordered state, preventing the formation of the long-range-ordered lamellar structure responsible for photonic properties. Applying modest anisotropic pressure (3 psi) between parallel plates at ambient temperature orients the short-range lamellar grains; however, applied pressure alone does not produce long-range order. Only when the bottlebrush block polymers were heated (>100 °C) under modest pressure (3 psi) were long-range-ordered photonic crystals formed. Analysis of the SAXS data motivated analogies to liquid crystals and revealed the potential self-assembly pathway. These results provide insight into the structure and self-assembly of bottlebrush block polymers with low glass transition temperature side chains in response to different processing conditions.

How to identify the optimum switch point of sequential invasive and noninvasive ventilation is the focus of clinical attention on the patients suffering from acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by acute respiratory failure (ARF). This study aims to explore the clinical significance of taking the change rate of procalcitonin (PCT) as identifying the timing of weaning on the mechanical ventilation for the patients of AECOPD followed by ARF as a complication. There were altogether 140 patients of AECOPD complicated with ARF, who were randomly selected and divided into a study group and a control group respectively. A change rate of serum PCT level exceeding 50% was taken as the switch point selection of tracheal intubation removal for the patients of the study group, while the 'pulmonary infection control (PIC) window' was done for those in the control group. With CRP, IL-6, TNF-a, PaCO 2, PaO 2, and Lac having been detected before and after treatment to them all, clinical indexes were obtained and compared between these two groups. The CRP, TNF-a, and IL-6 levels of the patients in the study group after treatment ( p < 0.05 ) were lower than those in the control group. There was no significant difference in PaCO 2, PaO 2, and Lac between these two groups before and after treatment ( p > 0.05 ). Even so, some other indexes available for the study group of patients were found to be lower than those for the control group ( p < 0.05 ) in the following aspects: duration of invasive ventilation support, total time of mechanical ventilation support, incidence rate of ventilator-associated pneumonia, 48-hour reintubation rate, incidence rate of upper gastrointestinal bleeding, hospitalization time of critical respiratory illness, total hospitalization time, RICU treatment cost, total treatment cost, and mortality. It is preferable to take the change rate of PCT level exceeding 50% as the switch point of weaning time in sequential mechanical ventilation rather than the PIC window. AbbreviationsAECOPD: acute exacerbation of chronic obstructive pulmonary disease; ARF: acute respiratory failure; PCT: procalcitonin; PaO 2 : the oxygen partial pressure; PaCO 2 : the partial pressure of carbon dioxide; TNF-a: serum tumor necrosis factor-a; IL-6: interleukin-6; CRP: serum C-reactive protein; PIC window: pulmonary infection control window; RICU: respiration and intensive care unit.

Purpose: To examine the benefits and feasibility of a mobile, real-time, community-based, teleophthalmology program for detecting eye diseases in the New York metro area., Design: Single site, nonrandomized, cross-sectional, teleophthalmologic study., Methods: Participants underwent a comprehensive evaluation in a Wi-Fi-equipped teleophthalmology mobile unit. The evaluation consisted of a basic anamnesis with a questionnaire form, brief systemic evaluations and an ophthalmologic evaluation that included visual field, intraocular pressure, pachymetry, anterior segment optical coherence tomography, posterior segment optical coherence tomography, and nonmydriatic fundus photography. The results were evaluated in real-time and follow-up calls were scheduled to complete a secondary questionnaire form. Risk factors were calculated for different types of ophthalmological referrals., Results: A total of 957 participants were screened. Out of 458 (48%) participants that have been referred, 305 (32%) had glaucoma, 136 (14%) had narrow-angle, 124 (13%) had cataract, 29 had (3%) diabetic retinopathy, 9 (1%) had macular degeneration, and 97 (10%) had other eye disease findings. Significant risk factors for ophthalmological referral consisted of older age, history of high blood pressure, diabetes mellitus, Hemoglobin A1c measurement of ≥6.5, and stage 2 hypertension. As for the ocular parameters, all but central corneal thickness were found to be significant, including having an intraocular pressure >21 mm Hg, vertical cup-to-disc ratio ≥0.5, visual field abnormalities, and retinal nerve fiber layer thinning., Conclusions: Mobile, real-time teleophthalmology is both workable and effective in increasing access to care and identifying the most common causes of blindness and their risk factors., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Chronic inflammation, long implicated in the genesis of malignancy, is now understood to underlie an estimated 25% of all cancers. The most pertinent malignancies, to the plastic surgeon, associated with the degeneration of chronic inflammation include Marjolin's ulcer, breast implant-associated large cell lymphoma, radiation-induced sarcoma, and Kaposi's sarcoma. The cellular and genetic damage incurred by a prolonged inflammatory reaction is controlled by an increasingly understood cytokinetic system. Advances in understanding the chronic inflammatory cascade have yielded new therapeutics and therapeutic targets., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Negative pressure wound therapy (NPWT) promotes healing by evenly applying negative pressure on the surface of the wound. The system consists of a sponge, a semiocclusive barrier, and a fluid collection system. Its effectiveness is explained by four main mechanisms of action, including macrodeformation of the tissues, drainage of extracellular inflammatory fluids, stabilization of the environment of the wound, and microdeformation. Rarely will complications linked to NPWT occur, but special care must be taken to prevent events such as toxic shock syndrome, fistulization, bleeding, and pain. New NPWT modalities have been recently developed to make NPWT suitable for a wider variety of wounds. These include NPWT with instillation therapy (NPWTi-d), different cleansing options, and application of NPWT on primarily closed incisions. Finally, vacuum-assisted wound closure therapy has been demonstrated to be efficient for various clinical settings, such as the management of diabetic foot ulcers, pressure ulcerations, chronic wounds, and skin grafts., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Over 400,000 women in the United States alone will have breast implant surgery each year. Although capsular contracture represents the most common complication of breast implant surgery, surgeons continue to debate the precise etiology. General agreement exists concerning the inflammatory origin of capsular fibrosis, but the inciting events triggering the inflammatory cascade appear to be multifactorial, making it difficult to predict why one patient may develop capsular contracture while another will not. Accordingly, researchers have explored many different surgical, biomaterial, and medical therapies to address these multiple factors in an attempt to prevent and treat capsular contracture. In the current paper, we aim to inform the reader on the most up-to-date understanding of the pathophysiology, prevention, and treatment of capsular contracture., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Summary: The progress of biotechnology, medical instruments, and applied sciences contributes to a rapidly expanding space for the advancement of the medical field. Surgeons experience first-hand the limitations of current medical devices and thus have unique insight into problems that could be solved with new products. The process of turning an idea into a product capable of success in the marketplace, however, is often unfamiliar to surgeons. The authors seek to illuminate this process and provide an ordered list of tasks that can make bringing ideas to market more achievable for surgeons. The first step in this process is the generation and protection of a new idea. Next, the process of making an idea into a product is outlined. This phase involves team assembly, business planning, and product development. Market research and valuation are key to understanding how a product can be applied in the market, and meticulous research during this phase allows for informed decision-making that will help secure funding down the road. Finally, various options for financing are discussed and compared to help surgeon-entrepreneurs find an option that best fits their project, and steps to maximize leverage are described. The development of new products can be a complicated process for surgeons. Organized into four phases, with ordered instructional steps to advance through each phase, the process of bringing an idea to the market is clarified. Facilitating this process will possibly contribute to the continual improvement of medical and surgical abilities through the introduction of new devices and technologies., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: The patient suffering from urinary sepsis is often accompanied by elevated serum procalcitonin (PCT) levels and a decline in the average platelet count (PLT), which could result in a poor prognosis. This study aimed to evaluate the value of PCT and PLT in determining the severity of urinary sepsis., Methods: A total of 120 urosepsis patients enrolled were divided into a survival group and a death group, respectively, according to their status within 14 days after admission. Changes in PCT and PLT levels between the 2 groups were compared at different time points. A receiver operating characteristic (ROC) curve was eventually obtained to predict the prognostic value of PCT and PLT., Results: The PCT levels in the survival group declined gradually after admission, and the PLT decreased at first but increased rapidly in subsequence. The PCT level in the death group, however, declined in a flat-slope trend or was hardly noticeable together with the number of PLT reduced significantly. In particular, it is on the 3rd day that PCT tended to positively correlate with acute physiological and chronic health score II (APACHE II) score (r = 0.730, P < .05), but negatively with PLT (r = 0.472, P < .05). The APACHE II score and PLT (r = 0.612, P < .05) were also negatively correlated with each other. As indicated by the ROC curve, the PCT level on the 3rd day after admission was of great value for the clinical mortality prognosis, and the area under the curve was 0.858. Moreover, PLT also has a high predictive value for prognosis. Area under the curve is 0.951. When the PLT was more than 51 × 109 /L, the sensitivity was up to 90%, and the specificity was 90%., Conclusion: PLT and PCT levels are closely related to the APACHE II score, which could indicate the severity of urosepsis in patients. The contribution of this study was to confirm that dynamic monitoring of the changes in PCT and PLT helps determine the prognosis of urosepsis patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Although the profunda artery perforator flap has gained popularity in breast reconstruction, it has not been well described for reconstruction of head and neck defects. The authors report their experience with free profunda artery perforator flaps in postoncologic head and neck reconstruction., Methods: A retrospective review of all free profunda artery perforator flaps used for head and neck reconstruction from 2016 to 2019 was performed., Results: Overall, 61 profunda artery perforator flap reconstructions were performed: 45 single independent flaps, 12 in conjunction with a second free flap, and four in combination with two other free flaps. The profunda artery perforator flaps were most commonly used for reconstruction of the tongue (n = 19), cheek (n = 11), parotid (n = 10), and maxilla (n = 6). The profunda artery perforator flaps averaged 7.1 × 12.1 × 1.9 cm, with a mean pedicle length of 11.5 cm. The A, B, and C perforators were located at mean distances of 7.4 cm (range, 4 to 11.5 cm), 11.7 cm (range, 8 to 18 cm), and 16.1 cm (range, 14 to 20.5 cm) from the pubic tubercle along the axis of the adductor longus muscle and 7.9 cm (range, 7 to 11cm), 7.6 cm (range, 7 to 15.5 cm), and 7.2 cm (range, 6 to 16 cm) posterior and perpendicular to the axis. There were three partial flap losses. Eight patients (13 percent) had recipient-site complications necessitating operative intervention: four for vascular compromise of the profunda artery perforator flap, two for hematoma evacuation, and two for infection. Donor-site complications were noted in seven patients (11 percent), two of whom required operative intervention., Conclusions: The profunda artery perforator flap is a versatile and reliable flap with consistent anatomy and a low complication rate. The profunda artery perforator flap seems to be a reasonable alternative for reconstruction of head and neck defects., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Autologous fat grafting is an important tool in plastic surgery and is widely used for a variety of applications, both aesthetic and reconstructive. Despite an ever-increasing list of indications and extensive research over many years into improving outcomes, fat grafting remains plagued by incomplete and often unpredictable graft survival. Decisions made at each stage of surgery can potentially contribute to ultimate success, including donor site selection and preparation, fat harvest, processing, and purification of lipoaspirate, recipient site preparation, and delivery of harvested fat to the recipient site. In this review, we examine the evidence for and against proposed techniques at each stage of fat grafting. Areas of consensus identified include use of larger harvesting and grafting cannulas and slow injection speeds to limit cell damage due to shearing forces, grafting techniques emphasizing dispersion of fat throughout the tissue with avoidance of graft pooling, and minimizing exposure of the lipoaspirate to the environment during processing. Safety considerations include use of blunt-tipped needles or cannulas to avoid inadvertent intravascular injection as well as awareness of cannula position and avoidance of danger zones such as the subgluteal venous plexus. We believe that using the evidence to guide surgical decision-making is the key to maximizing fat grafting success. Level of Evidence: 4., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)