Nopp140-chaperoned 2'-O-methylation of small nuclear RNAs in Cajal bodies ensures splicing fidelity.

Spliceosomal small nuclear RNAs (snRNAs) are modified by small Cajal body (CB)-specific ribonucleoproteins (scaRNPs) to ensure snRNP biogenesis and pre-mRNA splicing. However, the function and subcellular site of snRNA modification are largely unknown. We show that CB localization of the protein Nopp140 is essential for concentration of scaRNPs in that nuclear condensate; and that phosphorylation by casein kinase 2 (CK2) at ∼80 serines targets Nopp140 to CBs. Transiting through CBs, snRNAs are apparently modified by scaRNPs. Indeed, Nopp140 knockdown-mediated release of scaRNPs from CBs severely compromises 2'-O-methylation of spliceosomal snRNAs, identifying CBs as the site of scaRNP catalysis. Additionally, alternative splicing patterns change indicating that these modifications in U1, U2, U5, and U12 snRNAs safeguard splicing fidelity. Given the importance of CK2 in this pathway, compromised splicing could underlie the mode of action of small molecule CK2 inhibitors currently considered for therapy in cholangiocarcinoma, hematological malignancies, and COVID-19.

On-Demand MXene-Coupled Pyroelectricity for Advanced Breathing Sensors and IR Data Receivers.

MXene-inspired two-dimensional (2D) materials like Ti3C2Tx are widely known for their versatile properties, including surface plasmon, higher electrical conductivity, exceptional in-plane tensile strength, EMI shielding, and IR thermal properties. The MXene nanosheets coupled poly(vinylidene fluoride) (PVDF) nanofibers with d33 ∼-26 pm V-1 are able to capture the smaller thermal fluctuation due to a superior pyroelectric coefficient of ∼130 nC m-2 K-1 with an improved (∼7 times with respect to neat PVDF nanofibers) pyroelectric current figure of merit (FOMi). The significant enhancement of the pyroelectric response is attributed to the confinement effect of 2D MXene (Ti3C2Tx) nanosheets within PVDF nanofibers, as evidenced from polarized Fourier transform infrared (FTIR) spectroscopy and scanning probe microscopy (SPM). In subsequent studies, the practical applications of self-powered pyroelectric sensors of MXene-PVDF have been demonstrated. The fabricated flexible, hydrophobic pyroelectric sensor could be utilized as an excellent pyroelectric breathing sensor, a proximity sensor, and an IR data transmission receiver. Further, supervised machine learning algorithms are proposed to distinguish different types of breathing signals with ∼98% accuracy for healthcare monitoring purposes.

Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes.

Somatic hypermutation (SHM) and class-switch recombination (CSR) of the immunoglobulin (Ig) genes allow B cells to make antibodies that protect us against a wide variety of pathogens. SHM is mediated by activation-induced deaminase (AID), occurs at a million times higher frequency than other mutations in the mammalian genome, and is largely restricted to the variable (V) and switch (S) regions of Ig genes. Using the Ramos human Burkitt's lymphoma cell line, we find that H3K79me2/3 and its methyltransferase Dot1L are more abundant on the V region than on the constant (C) region, which does not undergo mutation. In primary naïve mouse B cells examined ex vivo, the H3K79me2/3 modification appears constitutively in the donor Sµ and is inducible in the recipient Sγ1 upon CSR stimulation. Knockout and inhibition of Dot1L in Ramos cells significantly reduces V region mutation and the abundance of H3K79me2/3 on the V region and is associated with a decrease of polymerase II (Pol II) and its S2 phosphorylated form at the IgH locus. Knockout of Dot1L also decreases the abundance of BRD4 and CDK9 (a subunit of the P-TEFb complex) on the V region, and this is accompanied by decreased nascent transcripts throughout the IgH gene. Treatment with JQ1 (inhibitor of BRD4) or DRB (inhibitor of CDK9) decreases SHM and the abundance of Pol II S2P at the IgH locus. Since all these factors play a role in transcription elongation, our studies reinforce the idea that the chromatin context and dynamics of transcription are critical for SHM.

The role of HIRA-dependent H3.3 deposition and its modifications in the somatic hypermutation of immunoglobulin variable regions.

The H3.3 histone variant and its chaperone HIRA are involved in active transcription, but their detailed roles in regulating somatic hypermutation (SHM) of immunoglobulin variable regions in human B cells are not yet fully understood. In this study, we show that the knockout (KO) of HIRA significantly decreased SHM and changed the mutation pattern of the variable region of the immunoglobulin heavy chain (IgH) in the human Ramos B cell line without changing the levels of activation-induced deaminase and other major proteins known to be involved in SHM. Except for H3K79me2/3 and Spt5, many factors related to active transcription, including H3.3, were substantively decreased in HIRA KO cells, and this was accompanied by decreased nascent transcription in the IgH locus. The abundance of ZMYND11 that specifically binds to H3.3K36me3 on the IgH locus was also reduced in the HIRA KO. Somewhat surprisingly, HIRA loss increased the chromatin accessibility of the IgH V region locus. Furthermore, stable expression of ectopic H3.3G34V and H3.3G34R mutants that inhibit both the trimethylation of H3.3K36 and the recruitment of ZMYND11 significantly reduced SHM in Ramos cells, while the H3.3K79M did not. Consistent with the HIRA KO, the H3.3G34V mutant also decreased the occupancy of various elongation factors and of ZMYND11 on the IgH variable and downstream switching regions. Our results reveal an unrecognized role of HIRA and the H3.3K36me3 modification in SHM and extend our knowledge of how transcription-associated chromatin structure and accessibility contribute to SHM in human B cells.

SF3B1/Hsh155 HEAT motif mutations affect interaction with the spliceosomal ATPase Prp5, resulting in altered branch site selectivity in pre-mRNA splicing.

Mutations in the U2 snRNP component SF3B1 are prominent in myelodysplastic syndromes (MDSs) and other cancers and have been shown recently to alter branch site (BS) or 3' splice site selection in splicing. However, the molecular mechanism of altered splicing is not known. We show here that hsh155 mutant alleles in Saccharomyces cerevisiae, counterparts of SF3B1 mutations frequently found in cancers, specifically change splicing of suboptimal BS pre-mRNA substrates. We found that Hsh155p interacts directly with Prp5p, the first ATPase that acts during spliceosome assembly, and localized the interacting regions to HEAT (Huntingtin, EF3, PP2A, and TOR1) motifs in SF3B1 associated with disease mutations. Furthermore, we show that mutations in these motifs from both human disease and yeast genetic screens alter the physical interaction with Prp5p, alter branch region specification, and phenocopy mutations in Prp5p. These and other data demonstrate that mutations in Hsh155p and Prp5p alter splicing because they change the direct physical interaction between Hsh155p and Prp5p. This altered physical interaction results in altered loading (i.e., "fidelity") of the BS-U2 duplex into the SF3B complex during prespliceosome formation. These results provide a mechanistic framework to explain the consequences of intron recognition and splicing of SF3B1 mutations found in disease.

Partially Ion-Paired Solvation Structure Design for Lithium-Sulfur Batteries under Extreme Operating Conditions.

Achieving increased energy density under extreme operating conditions remains a major challenge in rechargeable batteries. Herein, we demonstrate an all-fluorinated ester-based electrolyte comprising partially fluorinated carboxylate and carbonate esters. This electrolyte exhibits temperature-resilient physicochemical properties and moderate ion-paired solvation, leading to a half solvent-separated and half contact-ion pair in a sole electrolyte. As a result, facile desolvation and preferential reduction of anions/fluorinated co-solvents for LiF-dominated interphases are achieved without compromising ionic conductivity (>1 mS cm-1 even at -40 °C). These advantageous features were found to apply to both lithium metal and sulfur-based electrodes even under extreme operating conditions, allowing stable cycling of Li || sulfurized polyacrylonitrile (SPAN) full cells with high SPAN loading (>3.5 mAh cm-2 ) and thin Li anode (50 µm) at -40, 23 and 50 °C. This work offers a promising path for designing temperature-resilient electrolytes to support high energy density Li metal batteries operating in extreme conditions.

Utilizing Strain-Engineered Stable Halide Perovskite for Interfacial Interaction with Molecular Dipoles To Enhance Ferroelectric Switching and Piezoresponse in Polymer Composite Nanofibers.

Mechanical and solar to electrical energy conversion using piezo- and ferroelectric and photovoltaic effects may be a practical answer to the rising energy demand. In this quest, piezoelectric polymer poly(vinylidene fluoride-hexafluoroproylene) (P(VDF-HFP)) has gained interest due to its superior piezo- and ferroelectricity. In photovoltaic applications, inorganic halide perovskite (IHP) of CsPbI3 is considered a prime model compound. However, its application is limited because of the photoactive perovskite phase instability at ambient conditions. Here, we report the in situ synthesis of the stable perovskite γ-CsPbI3 through an electrospinning process at room temperature, encapsulated within a ferroelectric copolymer poly(vinylidene fluoride-hexafluoroproylene) (P(VDF-HFP)) as a composite nanofiber. Computational calculation using density functional theory (DFT) reveals that tensile strain plays a critical role in the dynamical stabilization of γ-CsPbI3. This tensile strain is triggered by the electrospinning process, which aids in the formation and growth of γ-CsPbI3. In the CsPbI3-P(VDF-HFP) composite nanofiber, γ-CsPbI3 nucleates the polar ß-crystalline phase in P(VDF-HFP), which results in the intrinsic piezo- and ferroelectric characteristics. The γ-CsPbI3 aids in preferable molecular dipole orientation, resulting in improved nanoscale piezo- and ferroelectric properties. The composite nanofiber features a higher piezoelectric d33 magnitude (∼30 pm/V) and lower decay constant for polarized domains (τcomposite ≈ 17). The composite was utilized as a piezoelectric nanogenerator to demonstrate human physiological motion monitoring in self-power mode. The relevant pressure sensitivities of 81 and 40 mV/kPa for the low-pressure (<0.6 kPa) and high-pressure (>0.6 to 12 kPa) ranges, respectively, promise its suitability in the health care sector.

Does Brow Lift Add Risk to Blepharoplasty? Answers From a Multicenter Analysis of 6126 Patients Undergoing Aesthetic Eye Surgery.

BACKGROUND: Browlift is frequently combinedwith blepharoplasty; however, the literature is lacking on their combined effect on complication rates. OBJECTIVES: This study aims to evaluate major complication rates after blepharoplasty and brow lift and to determine if complication rates increase when blepharoplasty and brow lift were performed simultaneously. METHODS: A prospective cohort of patients who underwent cosmetic blepharoplasty, brow lift, or a combination of the 2 procedures between 2008 and 2013 was identified from the CosmetAssure Insurance database. The primary outcome was a postoperative major complication requiring emergency room evaluation, hospital admission, or reoperation within 30 days. Groups were compared with univariate analysis (significance, P < 0.05). RESULTS: A total of 6126 patients underwent aesthetic eye surgery, of which, 4879 (79.6%) underwent blepharoplasty, 441 (7.2%) brow lift, and 806 (13.2%) a combination the 2 procedures. Patients who underwent a combined procedure were older than patients who underwent isolated blepharoplasty or brow lift (55.5 ± 9.4 vs 54.6 ± 11.1 vs 53.3 ± 12.0 years; P < 0.01). In males, blepharoplasty was the most commonly performed procedure, followed by a combined procedure and brow lift (17.6% vs 12.9% vs 10.7%; P < 0.01). There were similar rates of smokers between the 3 groups (5.7% vs 8.0% vs 6.6%; P = 0.06). Between combined procedures, blepharoplasty, and brow lift there, were similar rates of major complications (0.4% vs 0.4% vs 0.7%; P = 0.65) and hematoma (0.2% vs 0.2% vs 0.5%; P = 0.49), which was the most common complication. CONCLUSIONS: Aesthetic eye surgery has a very low overall major complication rate (0.4%). When brow lift is combined with blepharoplasty, it poses no additional risk of major complications compared with either procedure alone.

Ddx41 inhibition of DNA damage signaling permits erythroid progenitor expansion in zebrafish.

DEAD-box Helicase 41 (DDX41) is a recently identified factor mutated in hematologic malignancies whose function in hematopoiesis is unknown. Using an in vivo model of Ddx41 deficiency, we unveiled a critical role for this helicase in regulating erythropoiesis. We demonstrated that loss of ddx41 leads to anemia caused by diminished proliferation and defective differentiation of erythroid progenitors. Mis-expression and alternative splicing of cell cycle genes is rampant in ddx41 mutant erythroid progenitors. We delineated that the DNA damage response is activated in mutant cells resulting in an Ataxiatelangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-related (ATR)-triggered cell cycle arrest. Inhibition of these kinases partially suppressed ddx41 mutant anemia. These findings establish a critical function for Ddx41 in promoting healthy erythropoiesis via protection from genomic stress and delineate a mechanistic framework to explore a role for ATM and ATR signaling in DDX41-mutant hematopoietic pathologies.

Lead-Free Perovskite Cs3Bi2I9-Derived Electroactive PVDF Composite-Based Piezoelectric Nanogenerators for Physiological Signal Monitoring and Piezo-Phototronic-Aided Strain Modulated Photodetectors.

In recent years, lead-free perovskite materials are exponentially emerging in photovoltaic and optoelectronic applications due to their low toxicity and superior optical properties. On the other hand, the demand for flexible, wearable, and lightweight optoelectronic devices is significantly growing in sensor and actuator technologies. In this scenario, lead-free perovskite-based flexible piezoelectric polymer composites have sparked considerable attention in this field due to their excellent piezo-, pyro-, ferroelectric, and photovoltaic properties. Thus, in this work, a long-term stable lead-free Cs3Bi2I9-PVDF composite is introduced. The in situ growth of the Cs3Bi2I9 perovskite induces 92% yield of the electroactive phase in the PVDF matrix. The possible mechanism behind the electroactive ß-phase transformation is presented via interfacial interactions of PVDF moieties with the Cs3Bi2I9 (CBI) perovskite, which also give rise to long-term environmental stability. Next, a piezoelectric nanogenerator (PNG) has been fabricated with the Cs3Bi2I9-PVDF composite for mechanical energy harvesting, biophysiological motion monitoring, and voice recognitions that have potential utility in the health-care sector. Furthermore, a photodetector is developed to realize the piezo-phototronic effect. It exhibits a fast photoswitching behavior with rise and decay times of 141 and 278 ms, respectively. Thus, it is confirmed that the flexible Cs3Bi2I9-PVDF composite has shown tremendous potential to be used as an optical signal-modulated piezo-responsive wearable sensor.

Safety of a Protective Funnel in Primary Breast Augmentation: A Retrospective Analysis of 380 Multicenter Cases in the United States.

BACKGROUND: Protective funnel devices are commonly used to deliver implants in primary breast augmentation (BA) yet there is a paucity of evidence-based data describing their safety in the literature. OBJECTIVES: The purpose of this study was to assess the safety of protective funnels in primary BA within the first 30 days postoperatively. METHODS: This multicenter, Level 3 study retrospectively reviewed the surgical records of 380 consecutive patients (760 breasts) who underwent primary BA by 9 board-certified plastic surgeons using the iNPLANT Funnel (Proximate Concepts LLC, Allendale, NJ) for implant delivery between November 2019 and December 2020. Data were collected pertaining to demographics, implant information, surgery details, and postoperative complications. RESULTS: The mean patient age was 33 years and 76% of patients had a BMI <25 kg/m2. Of this cohort, 11.4% were smokers, 0.8% had diabetes, and 83% were ASA Class 1. All patients received smooth implants with a median volume of 375 cc. A total of 8 (2.1%) complications were reported, including 3 hematomas (0.79%), 1 seroma (0.26%), and 1 superficial infection (0.26%). No patient required explantation. We identified ASA class, BMI, surgery duration, and implant size as potential risk factors. CONCLUSIONS: The data suggest that the use of protective funnels, such as the iNPLANT Funnel, in primary BA is a safe option when these are utilized according to the manufacturer's Instructions for Use. The use of this device led to a low infection rate (0.26%) and a complication rate of (2.1%) consistent with the average reported in the literature (2%-2.5%).1 Implications for clinical practice are encouraging and future research will include a prospective analysis with a larger case series and potentially a control group.

Competitive pricing of substitute products under supply disruption.

There has been an increased interest in optimizing pricing and sourcing decisions under supplier competition with supply disruptions. In this paper, we conduct an analytical game-theoretical study to examine the effects of supply capacity disruption timing on pricing decisions for substitute products in a two-supplier one-retailer supply chain setting. We investigate whether the timing of a disruption may significantly impact the optimal pricing strategy of the retailer. We derive the optimal pricing strategy and ordering levels with both disruption timing and product substitution. By exploring both the Nash and Stackelberg games, we find that the order quantity with the disrupted supplier depends on price leadership and it tends to increase when the non-disrupted supplier is the leader. Moreover, the equilibrium market retail prices are higher under higher levels of disruption for the Nash game, compared to the Stackelberg game. We also uncover that the non-disrupted supplier can always charge the highest wholesale price if a disruption occurs before orders are received. This highlights the critical role of order timing. The insights can help operations managers to proper design risk mitigation ordering strategies and re-design the supply contracts in the presence of product substitution under supply disruptions.

Severe terminal ileitis induced by single-agent nivolumab administered every four weeks.

INTRODUCTION: Use of immune checkpoint inhibitors has expanded to a variety of malignancies including hepatocellular carcinoma, where nivolumab and pembrolizumab have shown durable responses in approximately a sixth of patients. CASE REPORT: We report herein a patient with metastatic hepatocellular carcinoma who achieved a durable response to the second-line agent nivolumab administered intravenous 240 mg every two weeks. After 18 months of therapy, nivolumab schedule was changed to intravenous 480 mg every four weeks, per patient's request and for convenience of administration. Four days after this change, the patient developed severe terminal ileitis.Management and outcome: This condition was managed in hospital with intravenous steroids. The patient improved clinically and was discharged on an oral steroid taper. A month later, nivolumab was reinstated at 200 mg intravenous infusions every two weeks, without any re-occurrence of terminal ileitis to date as of six months after the probable drug reaction. DISCUSSION: To our knowledge, this is the first report of terminal ileitis with nivolumab administered every four weeks. As postmarketing evaluation of nivolumab continues, similar side effects may be observed. Prompt diagnosis and steroid therapy in these cases are imperative to ensure a favorable outcome. Resuming immunotherapy once the adverse event has resolved appears to be a safe option.

Shallow floating treatment wetland capable of sulfate reduction in acid mine drainage impacted waters in a northern climate.

Floating treatment wetlands (FTW)s that can uptake nutrients and metals from water, and/or trap suspended solids in their roots, are becoming viable options to treat urban, agriculture and sewage runoffs. However, current FTW designs favor aerobic processes and short-term storage of metals, which are ineffective in acid mine drainage (AMD) environments. Many also function poorly in northern latitudes with strong seasonality and several months of sub-zero temperatures. In this study, we designed a novel FTWs with 20 cm soil profile to test its ability to sustain anaerobic microbial processes, such as iron and sulfate reduction and remain functional after freezing conditions of winter months. Three different plants, Carex lacustris, Typha latifolia, and Juncus canadensis were used to test in our FTWs, which were deployed in a mining-impacted water in Sudbury, ON, Canada. Porewater samples were acquired using built-in porewater peepers. Low to moderately reducing conditions, along with presence of ferrous iron and hydrogen sulfide in the porewater of all FTWs was prevalent, irrespective of the constituent vegetation type. Moreover, as well as a ~30% increase in sulfate-reducing bacteria (SRB) richness and ~100% increase in SRB abundance between years, was the evidence that anaerobic processes were occurring in these shallow FTWs. From this study we estimated that during its lifetime, one shallow FTW can treat ~61 m3 of sulfate-rich water, thus offering an alternative way to capture sulfate and other metals from mining-impacted waters.

Improvement in Brazilian Butt Lift (BBL) Safety With the Current Recommendations from ASERF, ASAPS, and ISAPS.

BACKGROUND: In 2017, the ASERF Gluteal Fat Grafting Task Force reported gluteal fat grafting to be a high-risk procedure and recommended specific surgical techniques to decrease the risk of pulmonary fat embolism (PFE). OBJECTIVES: The aim of this study was to determine whether ASAPS and ISAPS members were aware of the 2017 recommendations, what their current surgical techniques were, whether they had changed their techniques based on the 2017 recommendations, and whether the incidence of PFEs had changed since the recommendations were published. METHODS: An anonymous web-based survey was conducted among members of ASAPS and ISAPS. It included the questions from the 2017 survey, as well as questions about awareness of the Task Force recommendations and subsequent change in surgical techniques. RESULTS: In the 2 years following the publication of the recommendations, the incidence of any PFE was 1 in 2492 compared with 1 in 1030 reported in 2017 (P = 0.02). Trends indicated a decreased mortality rate from 1 in 3448 in 2017 to 1 in 14,952 in 2019. Ninety-four percent of respondents were aware of the recommendations. Only 0.8% of surgeons in the current survey reported injecting in deep muscle, compared with 13.1% in 2017 (P < 0.01). Compared with 4.1% in 2017, 29.8% of respondents in our survey reported that they only injected with cannulas ≥4.1 mm (P < 0.01). Only 4% of respondents reported angling the cannula down in the current survey, compared with 27.2% in 2017 (P < 0.01). CONCLUSIONS: It appears that members were aware of the 2017 recommendations. There was a significant decrease in recent PFE and trends showed a change to safer techniques and an improvement in safety of the procedure.

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release.

Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse.

Severe left atrial enlargement due to carfilzomib use in multiple myeloma.

Several cardiovascular effects have been attributed to carfilzomib in the recent literature. These side effects must be recognized promptly by treating physicians and pharmacists. Special attention is required in patients with pre-existing cardiac conditions, liver function abnormalities and/or advanced age. This is the first report of a severe left atrial enlargement due to carfilzomib use in the setting of multiple myeloma. This condition improved dramatically seven months after cessation of carfilzomib. The authors discuss further various cardiac and vascular abnormalities linked with carfilzomib in the medical literature. Prompt withdrawal of this agent is essential in these cases as it may prevent dismal outcomes.

Oral Delivery of Methylthioadenosine to the Brain Employing Solid Lipid Nanoparticles: Pharmacokinetic, Behavioral, and Histopathological Evidences.

The present study aimed to orally deliver methylthioadenosine (MTA) to the brain employing solid lipid nanoparticles (SLNs) for the management of neurological conditions like multiple sclerosis. The stearic acid-based SLNs were below 100 nm with almost neutral zeta potential and offered higher drug entrapment and drug loading. Cuprizone-induced demyelination model in mice was employed to mimic the multiple sclerosis-like conditions. It was observed that the MTA-loaded SLNs were able to maintain the normal metabolism, locomotor activity, motor coordination, balancing, and grip strength of the rodents in substantially superior ways vis-à-vis plain MTA. Histopathological studies of the corpus callosum and its subsequent staining with myelin staining dye luxol fast blue proved the potential of MTA-loaded SLNs in the remyelination of neurons. The pharmacokinetic studies provided the evidences for improved bioavailability and enhanced bioresidence supporting the pharmacodynamic findings. The studies proved that SLN-encapsulated MTA can be substantially delivered to the brain and can effectively remyelinate the neurons. It can reverse the multiple sclerosis-like symptoms in a safer and effective manner, that too by oral route.

The Effect of Smoking in the Cosmetic Surgery Population: Analysis of 129,007 Patients.

Background: Smoking has been associated with several postoperative adverse outcomes across multiple surgical disciplines, but the literature is limited for aesthetic surgical procedures. Objectives: To compare complication rates between smokers and nonsmokers undergoing common cosmetic procedures, identify specific cosmetic procedures where smoking increases the risk of complications, and evaluate smoking as an independent risk factor for major complications following aesthetic surgery. Methods: A prospective cohort of patients undergoing cosmetic surgery between 2008 and 2013 was identified from the CosmetAssure database. Smoking was evaluated as a risk factor for major complications requiring emergency room visit, hospital admission, or reoperation within 30 days after surgery. Multivariate regression analysis was performed controlling for the effects of age, gender, body mass index, type of surgical facility, type of procedure, and combined procedures. Results: Of the 129,007 patients, 10,621 (8.2%) were smokers. All procedures examined, except breast augmentation, were more frequently performed in the nonsmoker cohort. Overall major complications were similar between smokers and nonsmokers (2.0% vs 1.9%, P = 0.57). In univariate analysis, surgical site infections (0.6% vs 0.5%, P = 0.04) were significantly higher among smokers, but suspected venous thromboembolism (0.2% vs 0.1%, P = 0.01) was significantly higher among nonsmokers. Notably, smokers had a higher risk of major complications after body procedures (2.9% vs 1.0%, P = 0.01), as well as thigh lifts (23.8% vs 3.6%, P < 0.01) and male breast surgery (3.7% vs 1.4%, P = 0.03). In multivariate analysis, smoking was found to be an independent predictor of surgical site infections (relative risk 1.61, P < 0.01). Conclusions: Smoking is an independent risk factor of major surgical site infections following aesthetic surgery. Body procedures, as well as thigh lifts and male breast surgery, have higher complication rates in smokers.

Aesthetic Surgical Procedures in Men: Major Complications and Associated Risk Factors.

BACKGROUND: The number of men undergoing cosmetic surgery is increasing in North America. OBJECTIVES: To determine the incidence and risk factors of major complications in males undergoing cosmetic surgery, compare the complication profiles between men and women, and identify specific procedures that are associated with higher risk of complications in males. METHODS: A prospective cohort of patients undergoing cosmetic surgery between 2008 and 2013 was identified from the CosmetAssure database. Gender specific procedures were excluded. Primary outcome was occurrence of a major complication in males requiring emergency room visit, hospital admission, or reoperation within 30 days of the index operation. Univariate and multivariate analysis evaluated potential risk factors for major complications including age, body mass index (BMI), smoking, diabetes, type of surgical facility, type of procedure, and combined procedures. RESULTS: Of the 129,007 patients, 54,927 underwent gender nonspecific procedures, of which 5801 (10.6%) were males. Women showed a higher mean age (46.4 ± 14.1 vs 45.2 ± 16.7 years, P < 0.01). Men had a higher BMI (27.2 ± 4.7 vs 25.7 ± 4.9 kg/m2, P < 0.01), and were more likely to be smokers (7.1% vs 5.7%, P < 0.01) when compared to women. Men demonstrated similar overall major complication rates compared to women (2.1% vs 2.1%, P = 0.97). When specific complications were analyzed further, men had higher hematoma rates, but lower incidence of surgical site infection. Additionally, major complications after abdominoplasty, facelift surgery, and buttock augmentation were noted to preferentially affect males. On multivariate analysis, independent predictors of major complications in males included BMI (RR 1.05), hospital or ambulatory surgery center procedures (RR 3.47), and combined procedures (RR 2.56). CONCLUSIONS: Aesthetic surgery in men is safe with low major complication rates. Modifiable predictors of complications included BMI and combined procedures.