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Background: The National Surgical Quality Improvement Program (NSQIP) database provides an important resource for determining complication rates and risk factors for surgical procedures. However, NSQIP is limited to 30-day follow-up, and it is unclear whether this is reliable for evaluating prosthetic breast reconstruction outcomes., Methods: A single-institution, cross-sectional, retrospective review was performed for patients undergoing mastectomy with immediate, prepectoral tissue expander reconstruction. Timing of complications was stratified as early (within 30 days of operation) versus late (after 30 days). Categorical variables were compared using χ 2 (or Fisher exact) tests, and continuous variables were analyzed using Kruskal-Wallis or Wilcoxon rank-sum tests., Results: There were 301 patients (509 reconstructed breasts) included with a median follow-up time of 11 months. Of them, 176 patients (58%) experienced a postoperative complication-140 patients (47%) experienced an early complication and 36 patients (12%) experienced a late complication. Patients with late complications had a significantly higher rate of reconstructive failure compared with the early complication group (17% versus 10%; P = 0.001) and were more likely to require a flap (28% versus 7%; P = 0.001) for final reconstruction. Revision surgery rates after final implant placement were higher in the late complication group (36% versus 64%; P = 0.285)., Conclusions: Late complications after prepectoral breast reconstruction have a more prominent impact on reconstructive failure and revisions than early complications. This finding may inform strategies to revise national databases such as NSQIP to include more detailed information and longer capture periods., Competing Interests: Dr. Hollenbeck is co-founder of InSoma Bio, a startup company focused on improving fat grafting in the precommercial phase. The other authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Silicone gel removal after breast implant rupture is a difficult task. Silicone is hydrophobic and thus cannot be irrigated effectively with saline. Attempts at mechanical removal with sponges are often partially successful. Incomplete removal results in persistent silicone contamination with possible local inflammation, infection, and silicone granulomata. In this partially quantitative investigation, we assess the de-adhesion ability of different clindamycin formulations against known surfactant controls when combined with silicone gel., Methods: To demonstrate surfactant properties in vitro, clindamycin phosphate, clindamycin hydrochloride, and a known surfactant, sodium dodecyl sulfate (SDS), were compared. An amount of 170 g of silicone gel placed in a dry glass container exhibited strong adherence to the container walls. In separate trials, clindamycin phosphate (300 mg in 100 mL), clindamycin HCl (300 mg in 100 mL), and SDS (1 g in 100 mL) solutions with normal saline were added to the silicone aggregate, and de-adhesion properties were compared., Results: All solutions aided in the de-adhesion of the sticky silicone from glass substrate. The SDS had the strongest effect, followed by clindamycin phosphate and then clindamycin HCl. The observed interactions suggested that all of the solutions behaved as ionic surfactant coating the silicone with negative charges via adsorption. However, the phosphate anionic formulation was associated with a greater surfactant effect than HCl., Conclusions: Clindamycin acts as a surfactant to aid in the clinical removal of ruptured silicone gel. Clindamycin phosphate seems to have a stronger effect than clindamycin HCl, likely related to the negative charges on the phosphate groups., Competing Interests: The authors have no financial interest to declare in relation to the content of this article. The study was supported by the University of California Los Angeles., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Crushed cartilage grafts improve augmentation and contour irregularities in rhinoplasty; however, they are associated with complications including resorption, asymmetries, palpability, and need for revision surgery., Methods: A systematic review and meta-analysis following the preferred reporting items for systematic reviews and meta-analyses guidelines was performed on all recorded history up to November 2022 using the search query ("crush" or "crushed") AND cartilage AND rhinoplasty for PubMed, World of Science, Embase, and Cochrane online registries. Data were collected on study information, patient demographics, surgical details, and outcomes. Graft resorption and revision surgery were pooled in a random-effects model, and a subgroup analysis was performed for coverage/non-coverage of the cartilage and degree of crushing., Results: The initial search yielded 163 results, with 11 studies included in the final full-text review. A total of 1132 patients were analyzed, with 456 (40.3%) women, mean age of 48.0 years, and an average follow-up period of 24.9 months. Cartilage resorption rates were statistically higher in graft preparation using severely crushed cartilage (3.4%) compared to non-severely crushed cartilage (0.9%, p = 0.049). There was no significant difference in resorption rate for patients with covered cartilage graft (1.3%) compared to those with non-covered grafts (1.8%, p = 0.7). There were significantly more revision surgeries for severely crushed (17.9%) compared to non-severely crushed (3.5%, p = 0.003) cartilage grafts., Conclusions: Severely crushed cartilage grafting provides smooth contour and less palpability compared to other degrees of crushing but demonstrates significantly higher rate of resorption., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Mesh implants are frequently employed in alloplastic breast reconstruction. Notably, no mesh to date has FDA approval for this indication. Several synthetic meshes have been introduced with heterogeneous properties and outcomes., Objectives: This study aims to systematically review synthetic mesh use in alloplastic breast reconstruction, describe rates of short-term complications, and analyze these outcomes in reports comparing synthetic and biologic meshes. The authors hypothesized data from comparative and noncomparative studies would show no significant differences between synthetic and biological meshes., Methods: The authors conducted a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty-one studies reporting the use of synthetic mesh and clinical outcomes were included. Eight studies directly comparing synthetic mesh and biological mesh were meta-analyzed for relative risk (RR). Nineteen noncomparative studies were analyzed for meta-rates. Outcomes, including seroma, infection, reoperation, and explant, were assessed on a per-breast basis. Resultant models were challenged for sensitivity and bias., Results: Meta-analysis of comparative studies demonstrated no difference in the risk of infection with synthetic mesh (RR = 0.53; 95% CI [0.26-1.10]), but a reduced risk of reoperation (RR = 0.54; 95% CI [0.33-0.89]) or explant (RR = 0.43; 95% CI [0.21-0.87]). Meta-analysis of noncomparative studies demonstrated rates of seroma = 3%; 95% CI [1%-6%], infection = 4%; 95% CI [3%-6%], reoperation = 10%; 95% CI [7%-13%], and explant = 3%; 95% CI [2%-5%])., Conclusions: Studies comparing synthetic and biologic meshes demonstrated noninferiority of synthetic in all outcomes assessed. Noncomparative studies demonstrated rates of seroma, infection, reoperation, and explant similar to literature values for biological mesh., (Published by Oxford University Press on behalf of The Aesthetic Society 2024.)

Background: Enhanced recovery after surgery (ERAS) protocols have demonstrated success in reducing hospital stay and opioid consumption, but are less well studied in patients undergoing tissue expander-based breast reconstruction (TEBR). This study evaluates the effectiveness of an ERAS postoperative protocol for TEBR at a high-volume center., Methods: All patients undergoing immediate tissue expander reconstruction after the introduction of ERAS were prospectively included from April 2019 to June 2023. An equivalent number of similar patients were retrospectively reviewed before this date as the non-ERAS control. Data included demographics, operative details, postoperative length of stay, inpatient and discharge narcotic quantities, inpatient pain assessments, postoperative radiation, and complications within 90 days., Results: There were 201 patients in each cohort with statistically similar demographics. Patients in the ERAS cohort were more likely to undergo prepectoral reconstruction (83.1% versus 4.5%, P < 0.001), be discharged by day 1 (96.5% versus 70.2%, P < 0.001) and consume lower inpatient milligram morphine equivalent (MME) median (79.8 versus 151.8, P < 0.001). Seroma rates (17.4% versus 3.5%, P < 0.001) and hematoma incidence (4.5% versus 0%, P = 0.004) were higher in the ERAS cohort. Adjusting for implant location, ERAS was associated with a 60.7 MME reduction (β=-60.7, P < 0.001) and a shorter inpatient duration by 0.4 days (β =-0.4, P < 0.001). Additionally, prepectoral reconstruction significantly decreased MME (β=-30.9, P = 0.015) and was the sole predictor of seroma development (odds ratio = 5.2, P = 0.009)., Conclusions: ERAS protocols significantly reduce opioid use and hospital stay after TEBR., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Limited literature exists examining the effects of gender-affirming mastectomy on transmasculine and nonbinary patients that is prospective and uses validated survey instruments., Study Design: The psychosocial functioning of transmasculine and nonbinary patients was compared between patients who underwent gender-affirming mastectomy and those who had not yet undergone surgery. Participants were enrolled in a single-site, combined study of surgical and psychosocial outcomes, including a cross-sectional cohort of preoperative and postoperative patients, as well as separate prospective cohort. Participants completed the BREAST-Q psychosocial and sexual well-being modules, the BODY-Q satisfaction with chest and nipples modules, the Body Image Quality of Life Inventory, the Transgender Congruence Scale, the Patient Health Questionnaire-9, and the Generalized Anxiety Disorder-7 scale before and after surgery. We also examined how patient demographic factors correlated with postoperative surgical and psychosocial outcomes., Results: A total of 111 transmasculine and nonbinary patients 18 to 63 years of age (mean ± SD 26.5 ± 8) underwent mastectomy and were included in the study. All were included in the cross-sectional cohort, and 20 were enrolled in the prospective cohort. More than one-third (34.2%) of patients were nonbinary. After surgery, psychosocial and sexual well-being, satisfaction, body image-related quality of life, and gender congruence were increased (p < 0.001) in both cohorts, and depression (p < 0.009 cross-sectional), and anxiety (p < 0.001 cross-sectional) were decreased. The most common adverse event was hypertrophic scarring, which occurred in 41 (36.9%) participants., Conclusions: In this study of transmasculine and nonbinary adults, gender-affirming mastectomy was followed by substantial improvements in psychosocial functioning., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Enhanced recovery after surgery (ERAS) protocols have been associated with hypotensive episodes after autologous breast reconstruction. Gabapentin (Gaba), a nonopioid analgesic used in ERAS, has been shown to attenuate postoperative hemodynamic responses. This study assesses ERAS's impact, with and without Gaba, on postoperative hypotension after microvascular breast reconstruction., Methods: Three cohorts were studied: traditional pathway, ERAS + Gaba, and ERAS no-Gaba. We evaluated length of stay, inpatient narcotic use [morphine milligram equivalents (MME)], mean systolic blood pressure, hypotension incidence, and complications. The traditional cohort was retrospectively reviewed, whereas the ERAS groups were enrolled prospectively after the initiation of the protocol in April 2019 (inclusive of Gaba until October 2022)., Results: In total, 441 patients were analyzed. The three cohorts, in the order mentioned above, were similar in age and bilateral reconstruction rates (57% versus 61% versus 60%). The ERAS cohorts, both with and without Gaba, had shorter stays ( P < 0.01). Inpatient MME was significantly less in the ERAS + Gaba cohort than the traditional or ERAS no-Gaba cohorts (medians: 112 versus 178 versus 158 MME, P < 0.01). ERAS + Gaba significantly increased postoperative hypotensive events on postoperative day (POD) 1 and 2, with notable reduction after Gaba removal ( P < 0.05). Across PODs 0-2, mean systolic blood pressure was highest in the traditional cohort, followed by ERAS no-Gaba, then the ERAS + Gaba cohort ( P < 0.05). Complication rates were similar across all cohorts., Conclusions: Postmicrovascular breast reconstruction, ERAS + Gaba reduced overall inpatient narcotic usage, but increased hypotension incidence. Gaba removal from the ERAS protocol reduced postoperative hypotension incidence while maintaining similar stay lengths and complication rates., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Introduction: As reconstructive surgeons have increasingly transitioned to the prepectoral plane for prosthetic breast reconstruction, the implications of mastectomy skin flap necrosis have become more concerning. Our goal was to evaluate the effect of skin flap necrosis on reconstructive outcomes in patients undergoing immediate prepectoral breast reconstruction., Methods: A retrospective review was conducted of patients undergoing immediate two-stage prepectoral reconstruction at a single center with at least 3 months follow-up. Postoperative complications, reconstructive outcome, and time to final implant were compared between patients with and without mastectomy skin necrosis., Results: A total of 301 patients underwent 509 prepectoral breast reconstructions. Forty-four patients (14.6%) experienced postoperative mastectomy skin flap necrosis. Demographic and reconstructive characteristics were similar between the necrosis and no necrosis cohorts. Patients with skin necrosis were more likely to undergo reoperation after tissue expander (64% vs 19%, p < 0.01) and undergo expander replacement (13.6% vs 3.5%, p = 0.02). However, rates of reconstructive failure (6.8% vs 6.2%), major infection (9.1% vs 9.0%), and minor infection (13.6% vs 17.5%) after expander placement were statistically similar. Patients with skin necrosis trended toward longer time before final implant placement, although the difference was not statistically significant (6.5 vs 5.0 months, p = 0.08). There was no difference in complication rates between the necrosis and no necrosis cohort after final implant placement. There was a higher rate of revision surgery after implant placement in the necrosis cohort (12.5% vs 4.1%, p = 0.047)., Conclusions: Mastectomy skin flap necrosis is a concerning postoperative event, particularly in patients with prepectoral prostheses. We observed that patients with skin necrosis experience higher reoperation rates in the expander period, yet have similar infection rates and achieve similar final reconstructive outcomes compared to patients without necrosis., (Copyright © 2024. Published by Elsevier Ltd.)

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette's syndrome, the supplementary motor area in Parkinson's disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain., (© 2024. The Author(s).)

Background: Device classification and preclinical data requirements for animal-derived wound care products were recently reviewed by the FDA. Given the possible performance differences for these products, we evaluated the FDA data requirements as well as the published literature for all animal-derived wound care products ever cleared through the FDA., Study Design: The publicly available online database was queried for all animal-derived wound products; premarket data requirements for each product were recorded. A PubMed search was conducted to determine the number of published clinical studies for each product, and manufacturer websites were accessed to obtain the price for each product., Results: A total of 132 animal-derived wound products have been cleared by the FDA since the Center for Devices and Radiological Health was established in 1976. Of these, 114 had a publicly available clearance statement online. Preclinical biocompatibility testing was performed in 85 products (74.6%) and referenced in 10 (8.8%). Preclinical animal wound healing testing took place in 17 (14.9%). Only 9 products (7.9%) had clinical safety testing, and no products had clinical effectiveness data. We found no published peer-reviewed clinical data for 97 products (73%). Cost was infrequently available but ranged from $4.79 to $2,178 per unit., Conclusions: Although the current pathway is appropriate for efficiently clearing new wound care products, clinical effectiveness is not included in the regulatory review process. Wound care products are primarily evaluated by the FDA for safety and biocompatibility. Thus, any claims of clinical effectiveness require independent validation, which is often lacking., (Copyright © 2023 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: De Quervain's tenosynovitis is a relatively common, painful condition. Although commonly managed nonoperatively, some patients have recalcitrant disease, necessitating surgical release. Traditional surgical release for de Quervain's tenosynovitis with simple retinacular release can leave patients susceptible to first dorsal extensor compartment tendon subluxation. We present a stair-step flap technique that releases the first dorsal compartment while simultaneously preventing postoperative tendon subluxation via fascial lengthening., Methods: All patients over the past decade who underwent surgical release with this technique were collected. Preoperative characteristics, surgical details, and postoperative outcomes were reviewed and aggregated as summary statistics., Results: A total of 101 patients were found. Of these, 35 patients had isolated first dorsal compartment release. Tourniquet time for the total group was 1 hour and that for the isolated first dorsal compartment release subgroup was 20 minutes. The average follow-up was 590 days for the total group and only 440 days for the isolated first dorsal compartment release subgroup. No patients who underwent our novel technique experienced subluxation of the tendons postoperatively. One patient required oral antibiotics for a superficial cellulitis, and 1 patient had recurrent symptoms due to excessive scarring that resolved with scar massage and steroid injection. No patient required repeat operations., Conclusion: Our study demonstrates that first dorsal compartment release with a stair-step incision allows for closure of the compartment with a very loose sheath without subluxation and simultaneously provides satisfactory decompression. This procedure is safe and efficacious and can be considered a useful modification to traditional retinacular release alone., Level of Evidence: Level III., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Enhanced recovery after surgery (ERAS) protocols have demonstrated efficacy following microvascular breast reconstruction. This study assesses the impact of an ERAS protocol following microvascular breast reconstruction at a high-volume center., Methods: The ERAS protocol introduced preoperative counseling, multimodal analgesia, early diet resumption, and early mobilization to our microvascular breast reconstruction procedures. Data, including length of stay, body mass index, inpatient narcotic use, outpatient narcotic prescriptions, inpatient pain scores, and complications, were prospectively collected for all patients undergoing microvascular breast reconstruction between April 2019 and July 2021. Traditional pathway patients who underwent reconstruction immediately before ERAS implementation were retrospectively reviewed as controls., Results: The study included 200 patients, 99 in traditional versus 101 in ERAS. Groups were similar in body mass index, age (median age: traditional, 54.0 versus ERAS, 50.0) and bilateral reconstruction rates (59.6% versus 61.4%). ERAS patients had significantly shorter lengths of stay, with 96.0% being discharged by postoperative day (POD) 3, and 88.9% of the traditional cohort were discharged on POD 4 ( P < 0.0001). Inpatient milligram morphine equivalents (MMEs) were smaller by 54.3% in the ERAS cohort (median MME: 154.2 versus 70.4, P < 0.0001). Additionally, ERAS patients were prescribed significantly fewer narcotics upon discharge (median MME: 337.5 versus 150.0, P < 0.0001). ERAS had a lower pain average on POD 0-3; however, this finding was not statistically significant., Conclusion: Implementing an ERAS protocol at a high-volume microvascular breast reconstruction center reduced length of stay and postoperative narcotic usage, without increasing pain or perioperative complications., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The Le Fort I osteotomy is used to reposition the maxilla to correct numerous maxillofacial and occlusal deformities. The aim of this study was to delineate perioperative complication rates associated with Le Fort I osteotomy and determine whether the number of maxillary segments or bone grafting yielded increased complication rates. Patients undergoing Le Fort I osteotomy from 2012 to 2019 were identified from the multi-institution "National Surgical Quality Improvement Program" database using Current Procedure Terminology codes. The predictor variables of interest included maxillary segmentation defined as 1, 2, or 2 pieces and the presence or absence of bone graft. Perioperative complications were collected as the primary outcome variable, including superficial and deep space infections, wound dehiscence, airway complication, peripheral nerve injury, and hemorrhage. The secondary outcome variables included readmission and reoperation rate within the 30-day postoperative period. Complication rates were compared using multivariate analysis across groups stratified by the number of maxillary segments and inclusion of bone grafting. Of the 532 patients that met the inclusion criteria, 333 (63%) underwent 1-piece, 114 (21%) 2-piece, and 85 (16%) 2-piece Le Fort I osteotomy procedures. A total of 48 patients exhibited complications (9%), with hemorrhage (2.3%) being the most common complication observed. The number of maxillary segments was not a significant predictor of perioperative complications ( P = 0.948) nor was the use of bone grafting ( P = 0.279)., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Purpose: Dupuytren disease can be managed with an injection of collagenase Clostridium histolyticum enzyme followed by manual manipulation. Although the recommended time from injection to manipulation is 24-72 hours, patient and physician schedules may not accommodate this time frame. Therefore, we sought to study the impact of time from injection to manipulation on outcomes and complications of collagenase injection., Methods: We performed a review of 309 patients who underwent an injection of collagenase Clostridium histolyticum for Dupuytren disease with manipulation at two, five, or seven days after injection. We compared preinjection and postinjection contracture angles as well as frequency of skin tears and tendon ruptures., Results: Of the 309 patients, 207 underwent manipulation at two days, 32 at five days, and 70 at seven days. Patients had similar preinjection contracture angles. All patients demonstrated improvement in contracture after manipulation. Rates of skin tears and tendon ruptures were similar in all three groups. Significant predictors of complications included number of cords injected and history of previous collagenase injection, but not history of previous Dupuytren diagnosis., Conclusions: Although collagenase injection for Dupuytren disease is typically performed with plans for manipulation at 24-72 hours, postinjection manipulation could be performed as late as seven days without adversely affecting the frequency of skin and tendon complications., Type of Study/level of Evidence: Prognostic IV., (Copyright © 2023 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Breast reconstruction remains a major component of the plastic surgeon's repertoire, especially free-flap breast reconstruction (FFBR), though this is a high-risk surgery in which patient selection is paramount. Preoperative predictors of complication remain mixed in their utility. We sought to determine whether the sarcopenia score, a validated measure of physiologic health, outperforms the body mass index (BMI) and modified frailty index (mFI) in terms of predicting outcomes., Methods: All patients with at least 6-months follow-up and imaging of the abdomen who underwent FFBR from 2013 to 2022 were included in this study. Appropriate preoperative and postoperative data were included, and sarcopenia scores were extracted from imaging. Complications were defined as any unexpected outcome that required a return to the operating room or readmission. Statistical analysis and regression were performed., Results: In total, 299 patients were included. Patients were split into groups, based on sarcopenia scores. Patients with lower sarcopenia had significantly more complications than those with higher scores. BMI and mFI both did not correlate with complication rates. Sarcopenia was the only independent predictor of complication severity when other factors were controlled for in a multivariate regression model., Conclusions: Sarcopenia correlates with the presence of severe complications in patients who undergo FFBR in a stronger fashion to BMI and the mFI. Thus, sarcopenia should be considered in the preoperative evaluation in patients undergoing FFBR., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Background: Deep brain stimulation (DBS) for Parkinson's disease (PD) is generally contraindicated in persons with dementia but it is frequently performed in people with mild cognitive impairment or normal cognition, and current clinical guidelines are primarily based on these cohorts., Objectives: To determine if moderately cognitive impaired individuals including those with mild dementia could meaningfully benefit from DBS in terms of motor and non-motor outcomes., Methods: In this retrospective case-control study, we identified a cohort of 40 patients with PD who exhibited moderate (two or more standard deviations below normative scores) cognitive impairment (CI) during presurgical workup and compared their 1-year clinical outcomes to a cohort of 40 matched patients with normal cognition (NC). The surgery targeted subthalamus, pallidus or motor thalamus, in a unilateral, bilateral or staged approach., Results: At preoperative baseline, the CI cohort had higher Unified Parkinson's Disease Rating Scale (UPDRS) subscores, but similar levodopa responsiveness compared to the NC cohort. The NC and CI cohorts demonstrated comparable degrees of postoperative improvement in the OFF-medication motor scores, motor fluctuations, and medication reduction. There was no difference in adverse event rates between the two cohorts. Outcomes in the CI cohort did not depend on the target, surgical staging, or impaired cognitive domain., Conclusions: Moderately cognitively impaired patients with PD can experience meaningful motor benefit and medication reduction with DBS., (© 2023 International Parkinson and Movement Disorder Society.)

Use of acellular dermal matrices (ADMs) for tissue expander breast reconstruction remains controversial with an uncertain safety and efficacy profile. This study analyzes the rates and factors for reoperation and postoperative infection in patients who underwent tissue expander breast reconstruction with and without ADM., Methods: Patients who underwent breast reconstruction with and without ADM were identified from the National Surgical Quality Improvement Program database utilizing CPT codes. Covariates included patient demographics, preoperative comorbidities, and operative characteristics, while outcomes of interest were postoperative infection and reoperation. Univariate and multivariate analyses were performed to identify predictors of adverse outcomes., Results: There were 8334 patients in the ADM cohort and 12,451 patients who underwent tissue expander breast reconstruction without ADM. There were significantly fewer reoperations in the non-ADM cohort (5.4%) compared to the ADM cohort (7.7%) ( P < 0.0001), with infection and hematoma as the most common etiologies in both cohorts. Surgical infections were also more prevalent in the ADM cohort (4.7%) compared with the non-ADM cohort (3.6%) ( P < 0.0001). Univariate and multivariate analysis of the tissue expander breast reconstruction cohort revealed race, obesity, hypertension, smoking status, albumin, and operative time as predictive for infection risk, while race, obesity, hypertension, smoking, albumin, operative time, and age were significant for reoperation., Conclusion: Our study of 20,817 patients revealed significantly higher risk of infection and reoperation in patients who underwent breast reconstruction utilizing ADM versus without ADM. Patients considering ADM for breast reconstruction should engage in discussion with their surgeon about complications, aesthetics, and cost., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

It is not uncommon for physicians to think of ways to improve the delivery of care, which may take the form of a new medical device, drug, test, or service. In recent years, structured approaches to the identification of unmet needs and the development of solutions have been introduced to the medical community. Yet, due to gaps in exposure and training, there remains an opportunity to improve the level of understanding within the medical community regarding how to develop an innovation, once conceived, to the point of commercialization. The purpose of this article, therefore, is to provide an overview of some of the relevant considerations and requirements when bringing an idea for a new medical technology to market., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Background: While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility., Results: Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity., Conclusions: Thus, connecting genetically related traits across phenotypic scales links human diseases to molecular and cellular measurements that can reveal mechanisms and lead to novel biomarkers and therapeutic approaches. The iCPAGdb web portal is accessible at http://cpag.oit.duke.edu and the software code at https://github.com/tbalmat/iCPAGdb .

Background: In the past decade, surgeons have increasingly advocated for a return to prepectoral breast reconstruction with claims that surgical mesh (including acellular dermal matrix) can reduce complication rates. However, numerous surgical and implant advancements have occurred in the decades since the initial prepectoral studies, and it is unclear whether mesh is solely responsible for the touted benefits., Methods: The authors conducted a systematic review of all English language articles reporting original data for prepectoral implant-based breast reconstruction. Articles presenting duplicate data were excluded. Complications were recorded and calculated on a per-breast basis and separated as mesh-assisted, no-mesh prior to 2006, and no-mesh after 2006 (date of first silicone gel-filled breast implant approval). Capsular contracture comparisons were adjusted for duration of follow-up., Results: A total of 58 articles were included encompassing 3120 patients from 1966 to 2019. The majority of the included studies were retrospective case series. Reported complication outcomes were variable, with no significant difference between groups in hematoma, infection, or explantation rates. Capsular contracture rates were higher in historical no-mesh cohorts, whereas seroma rates were higher in contemporary no-mesh cohorts., Conclusions: Limited data exist to understand the benefits of surgical mesh devices in prepectoral breast reconstruction. Level I studies with an appropriate control group are needed to better understand the specific role of mesh for these procedures. Existing data are inconclusive but suggest that prepectoral breast reconstruction can be safely performed without surgical mesh., Competing Interests: Disclosure:The authors report no financial conflicts of interest. This study was not externally funded., (Copyright © 2020 by the American Society of Plastic Surgeons.)

Background: The central mound technique offers a relatively less common approach for breast reduction. This study evaluated the expected safety and efficacy outcomes using this technique in a large patient series., Methods: A retrospective review of all patients undergoing central mound breast reduction at the authors' institution between June of 1999 and November of 2018 was performed. Both bilateral macromastia and unilateral symmetrizing reduction patients were included but evaluated separately for some outcomes. Patient demographics and comorbidities, operative details, postoperative adverse events, and BREAST-Q scores were recorded. Associations between preoperative variables and outcomes were assessed with chi-square tests, Wilcoxon tests, and Kendall tau-b correlations., Results: A total of 325 patients were identified for inclusion (227 bilateral and 98 unilateral; 552 breasts). The average patient age was 46 years, and the average body mass index was 27.4 kg/m. Among the bilateral macromastia patients, the average operative time was 3 hours 34 minutes, and average breast tissue removed was 533 g (right breast) and 560 g (left breast). Among all patients, average follow-up was 169 days. On a per-breast basis for all patients, the following complication rates were observed: seroma, 0.2 percent; hematoma, 1.1 percent; dehiscence, 2.9 percent; infection, 1.5 percent; hypertrophic scar, 4.6 percent; nipple necrosis, 0.4 percent; fat necrosis, 0.9 percent; and skin flap necrosis, 1.7 percent. Using the BREAST-Q Reduction/Mastopexy questions on a Likert scale ranging from 1 to 5, restricted to the bilateral macromastia patient population, all scores improved with statistical significance., Conclusion: The central mound pedicle is a safe and effective approach for reduction mammaplasty for both bilateral macromastia patients and unilateral symmetrizing operations., Clinical Question/level of Evidence: Therapeutic, IV.

Background: Host defense peptides are a family of endogenous short peptides that are found in all living beings and play a critical role in innate immunity against infection., Methods: A nonsystematic review of host defense peptides was conducted with specific interest in properties and applications relevant to plastic and reconstructive surgery., Results: In addition to their direct antimicrobial actions against pathogens, including multidrug-resistant bacteria, they also demonstrate important functions in immunomodulation, tumor cell lysis, and tissue regeneration. These properties have made them a topic of clinical interest for plastic surgeons because of their potential applications as novel antibiotics, wound healing medications, and cancer therapies. The rising clinical interest has led to a robust body of literature describing host defense peptides in great depth and breadth. Numerous mechanisms have been observed to explain their diverse functions, which rely on specific structural characteristics. However, these peptides remain mostly experimental, with limited translation to clinical practice because of numerous failures to achieve acceptable results in human trials., Conclusions: Despite the broad ranging potential of these peptides for use in the field of plastic and reconstructive surgery, they are rarely discussed in the literature or at scientific meetings. In this review, the authors provide a summary of the background, structure, function, bacterial resistance, and clinical applications of host defense peptides with the goal of stimulating host defense peptide-based innovation within the field of plastic and reconstructive surgery.

Objective: Deep brain stimulation (DBS) lead placement is increasingly performed with the patient under general anesthesia by surgeons using intraoperative MRI (iMRI) guidance without microelectrode recording (MER) or macrostimulation. The authors assessed the accuracy of lead placement, safety, and motor outcomes in patients with Parkinson disease (PD) undergoing DBS lead placement into the globus pallidus internus (GPi) using iMRI or MER guidance., Methods: The authors identified all patients with PD who underwent either MER- or iMRI-guided GPi-DBS lead placement at Emory University between July 2007 and August 2016. Lead placement accuracy and adverse events were determined for all patients. Clinical outcomes were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) part III motor scores for patients completing 12 months of follow-up. The authors also assessed the levodopa-equivalent daily dose (LEDD) and stimulation parameters., Results: Seventy-seven patients were identified (MER, n = 28; iMRI, n = 49), in whom 131 leads were placed. The stereotactic accuracy of the surgical procedure with respect to the planned lead location was 1.94 ± 0.21 mm (mean ± SEM) (95% CI 1.54-2.34) with frame-based MER and 0.84 ± 0.007 mm (95% CI 0.69-0.98) with iMRI. The rate of serious complications was similar, at 6.9% for MER-guided DBS lead placement and 9.4% for iMRI-guided DBS lead placement (RR 0.71 [95% CI 0.13%-3.9%]; p = 0.695). Fifty-seven patients were included in clinical outcome analyses (MER, n = 16; iMRI, n = 41). Both groups had similar characteristics at baseline, although patients undergoing MER-guided DBS had a lower response on their baseline levodopa challenge (44.8% ± 5.4% [95% CI 33.2%-56.4%] vs 61.6% ± 2.1% [95% CI 57.4%-65.8%]; t = 3.558, p = 0.001). Greater improvement was seen following iMRI-guided lead placement (43.2% ± 3.5% [95% CI 36.2%-50.3%]) versus MER-guided lead placement (25.5% ± 6.7% [95% CI 11.1%-39.8%]; F = 5.835, p = 0.019). When UPDRS III motor scores were assessed only in the contralateral hemibody (per-lead analyses), the improvements remained significantly different (37.1% ± 7.2% [95% CI 22.2%-51.9%] and 50.0% ± 3.5% [95% CI 43.1%-56.9%] for MER- and iMRI-guided DBS lead placement, respectively). Both groups exhibited similar reductions in LEDDs (21.2% and 20.9%, respectively; F = 0.221, p = 0.640). The locations of all active contacts and the 2D radial distance from these to consensus coordinates for GPi-DBS lead placement (x, ±20; y, +2; and z, -4) did not differ statistically by type of surgery., Conclusions: iMRI-guided GPi-DBS lead placement in PD patients was associated with significant improvement in clinical outcomes, comparable to those observed following MER-guided DBS lead placement. Furthermore, iMRI-guided DBS implantation produced a similar safety profile to that of the MER-guided procedure. As such, iMRI guidance is an alternative to MER guidance for patients undergoing GPi-DBS implantation for PD.

Background: Acellular dermal matrix is used in most postmastectomy implant-based breast reconstructions in the United States. It is believed to be safe, despite a slightly increased complication rate. Although never established in a unifying study, the primary advantage of acellular dermal matrix is believed to be an enhanced aesthetic result, thus justifying the added expense. The purpose of this study was to assess the aesthetic benefits of acellular dermal matrix in expander-to-implant breast reconstruction., Methods: A systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was performed including all original studies examining aesthetic outcomes of expander-to-implant breast reconstructions with acellular dermal matrix compared to muscular coverage. Direct-to-implant and prepectoral studies were excluded from the evaluation. The results were aggregated and reported as a summary., Results: Among 883 studies identified, 49 full-text articles were reviewed and nine articles ultimately met inclusion criteria. All nine studies were not randomized. Of these, three articles (1448 total patients) evaluated reconstruction aesthetic outcomes by patient satisfaction, whereas six articles evaluated the aesthetic outcomes by external observer (504 total patients). None of the articles evaluating patient satisfaction reported a difference between acellular dermal matrix and muscular reconstruction. Five of the six articles using objective outcomes demonstrated significant improvement in aesthetic outcome in the acellular dermal matrix group., Conclusions: Although little evidence exists evaluating the aesthetic benefits of acellular dermal matrix for expander-to-implant breast reconstruction, the data suggest that objective observers consider acellular dermal matrix-assisted expander-to-implant breast reconstructions aesthetically superior to reconstruction with only muscular coverage, but patients appear to be equally satisfied with both reconstructive options.

The cerebellum is best known for its role in controlling motor behaviors. However, recent work supports the view that it also influences non-motor behaviors. The contribution of the cerebellum towards different brain functions is underscored by its involvement in a diverse and increasing number of neurological and neuropsychiatric conditions including ataxia, dystonia, essential tremor, Parkinson's disease (PD), epilepsy, stroke, multiple sclerosis, autism spectrum disorders, dyslexia, attention deficit hyperactivity disorder (ADHD), and schizophrenia. Although there are no cures for these conditions, cerebellar stimulation is quickly gaining attention for symptomatic alleviation, as cerebellar circuitry has arisen as a promising target for invasive and non-invasive neuromodulation. This consensus paper brings together experts from the fields of neurophysiology, neurology, and neurosurgery to discuss recent efforts in using the cerebellum as a therapeutic intervention. We report on the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define key hurdles and questions for moving forward.

Objective: Lead placement for deep brain stimulation (DBS) using intraoperative MRI (iMRI) relies solely on real-time intraoperative neuroimaging to guide electrode placement, without microelectrode recording (MER) or electrical stimulation. There is limited information, however, on outcomes after iMRI-guided DBS for dystonia. The authors evaluated clinical outcomes and targeting accuracy in patients with dystonia who underwent lead placement using an iMRI targeting platform., Methods: Patients with dystonia undergoing iMRI-guided lead placement in the globus pallidus pars internus (GPi) were identified. Patients with a prior ablative or MER-guided procedure were excluded from clinical outcomes analysis. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) scores and Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores were assessed preoperatively and at 6 and 12 months postoperatively. Other measures analyzed include lead accuracy, complications/adverse events, and stimulation parameters., Results: A total of 60 leads were implanted in 30 patients. Stereotactic lead accuracy in the axial plane was 0.93 ± 0.12 mm from the intended target. Nineteen patients (idiopathic focal, n = 7; idiopathic segmental, n = 5; DYT1, n = 1; tardive, n = 2; other secondary, n = 4) were included in clinical outcomes analysis. The mean improvement in BFMDRS score was 51.9% ± 9.7% at 6 months and 63.4% ± 8.0% at 1 year. TWSTRS scores in patients with predominant cervical dystonia (n = 13) improved by 53.3% ± 10.5% at 6 months and 67.6% ± 9.0% at 1 year. Serious complications occurred in 6 patients (20%), involving 8 of 60 implanted leads (13.3%). The rate of serious complications across all patients undergoing iMRI-guided DBS at the authors' institution was further reviewed, including an additional 53 patients undergoing GPi-DBS for Parkinson disease. In this expanded cohort, serious complications occurred in 11 patients (13.3%) involving 15 leads (10.1%)., Conclusions: Intraoperative MRI-guided lead placement in patients with dystonia showed improvement in clinical outcomes comparable to previously reported results using awake MER-guided lead placement. The accuracy of lead placement was high, and the procedure was well tolerated in the majority of patients. However, a number of patients experienced serious adverse events that were attributable to the introduction of a novel technique into a busy neurosurgical practice, and which led to the revision of protocols, product inserts, and on-site training.

Introduction: Image-guided navigation has existed for nearly 3 decades, but its adoption to craniofacial surgery has been slow. A systematic review of the literature was performed to assess the current status of navigation in craniofacial surgery., Methods: A Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) systematic review of the Medline and Web of Science databases was performed using a series of search terms related to Image-Guided Navigation and Craniofacial Surgery. Titles were then filtered for relevance and abstracts were reviewed for content. Single case reports were excluded as were animal, cadaver, and virtual data. Studies were categorized based on the type of study performed and graded using the Jadad scale and the Newcastle-Ottawa scales, when appropriate., Results: A total of 2030 titles were returned by our search criteria. Of these, 518 abstracts were reviewed, 208 full papers were evaluated, and 104 manuscripts were ultimately included in the study. A single randomized controlled trial was identified (Jadad score 3), and 12 studies were identified as being case control or case cohort studies (Average Newcastle-Ottawa score 6.8) The most common application of intraoperative surgical navigation cited was orbital surgery (n = 36), followed by maxillary surgery (n = 19). Higher quality studies more commonly pertained to the orbit (6/13), and consistently show improved results., Conclusion: Image guided surgical navigation improves outcomes in orbital reconstruction. Although image guided navigation has promise in many aspects of craniofacial surgery, current literature is lacking and future studies addressing this paucity of data are needed before universal adoption can be recommended.

Background: Breast implants have evolved for decades. In 2011, the U.S. Food and Drug Administration identified an association between textured breast implants and breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). The purpose of this study was to identify the trends of textured implant use since that time., Methods: Maintenance of Certification tracer data were queried between 2011 and 2015 for cosmetic breast augmentation cases submitted by American Board of Plastic Surgery diplomates. A nested random effects logistic regression analysis was used to identify associations between variables., Results: Eleven thousand seven hundred sixteen breast augmentations were performed by 880 unique surgeons. The overall proportion of cases using textured implants increased steadily from 2.3 percent in 2011 to 13.0 percent in 2015 (p < 0.001). The proportion of surgeons whose cases included both textured and smooth implants increased (from 6.2 percent to 24.3 percent), as did those using only textured implants (from 0.4 percent to 4.4 percent) (p < 0.001). Significance remained after controlling for form-stable implants, suggesting an alternative motivation for use of textured implants. Subglandular cases (20.5 percent) were more likely to use a textured implant than submuscular (8.4 percent) or dual-plane (7.8 percent) (p < 0.001) cases., Conclusions: Maintenance of Certification tracer data represent a random sampling of American Board of Plastic Surgery-certified plastic surgeons spanning the gamut of practice settings. Despite ongoing education regarding the association of BIA-ALCL with textured implants, American Board of Plastic Surgery diplomates have trended toward increased use of textured implants for cosmetic breast augmentation since 2011. This finding does not appear to be driven by the introduction of anatomical implants during the study period.

Background: A key educational component of the integrated plastic and reconstructive surgery (PRS) training model is the prerequisite, or core, experiences. The aim of this study is to assess the integrated PRS residents' experience with this early part of training., Methods: A 20-question survey was developed and piloted before deployment to integrated PRS training programs from 4 United States Census regions. Respondents were asked to characterize their prerequisite clinical and operative experiences. Results were analyzed using pairwise correlation statistics and logistic regression modeling following Bonferroni correction for multiple hypothesis testing., Results: One hundred ninety six residents (22 programs) participated in the study (response rate, 65.3%). The majority of residents were satisfied with their prerequisite experiences. Most did not take the American Board of Surgery In-Training Examination, which was perceived as noncontributory to PRS training. The majority of residents preferred to have fewer prerequisite experiences. Operative hours per week were predictive of resident satisfaction with the clinical and operative prerequisite experiences (both P < 0.001). Perception of general surgery program director investment in PRS education was also predictive of resident satisfaction with clinical and operative experiences (P = 0.05 and P < 0.001, respectively)., Conclusions: The present study demonstrates that PRS residents are satisfied with the quality of prerequisite training but prefer less overall. Reevaluation of the benefits of the American Board of Surgery In-Training Examination and individual essential rotations for resident education would be welcomed. Furthermore, this study identifies the residents' clinical and operative experience and perceived general surgery program director involvement as important determinants of integrated resident satisfaction with prerequisite training.

Pathogens have been a strong driving force for natural selection. Therefore, understanding how human genetic differences impact infection-related cellular traits can mechanistically link genetic variation to disease susceptibility. Here we report the Hi-HOST Phenome Project (H2P2): a catalog of cellular genome-wide association studies (GWAS) comprising 79 infection-related phenotypes in response to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome-wide significance for infection-associated phenotypes ranging from pathogen replication to cytokine production. We combined H2P2 with clinical association data from patients to identify a SNP near CXCL10 as a risk factor for inflammatory bowel disease. A SNP in the transcriptional repressor ZBTB20 demonstrated pleiotropy, likely through suppression of multiple target genes, and was associated with viral hepatitis. These data are available on a web portal to facilitate interpreting human genome variation through the lens of cell biology and should serve as a rich resource for the research community., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset., Methods: The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further., Results: UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT ( p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy ( p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT ( p = 0.001)., Conclusions: These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD., Classification of Evidence: This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor., (© 2018 American Academy of Neurology.)

Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely replaced by DBS of the subthalamic nucleus or internal pallidal segment. These procedures are not only effective in the treatment of parkinsonism, but also in the treatment of hyperkinetic conditions (such as chorea or dystonia) which result from pathophysiologic changes different from those underlying Parkinson's disease. Thus, these interventions probably do not counteract specific aspects of the pathophysiology of movement disorders, but non-specifically remove the influence of the different types of disruptive basal ganglia output from the relatively intact portions of the motor circuitry downstream from the basal ganglia. Knowledge gained from studies in NHPs remains critical for our understanding of the pathophysiology of movement disorders, of the effects of DBS on brain network activity, and the development of better treatments for patients with movement disorders and other neurologic or psychiatric conditions.

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Introduction: The latissimus dorsi (LD) myocutaneous flap has been a long term standard for breast reconstruction. The variable indications for the LD flap have not been statistically examined because of the relative infrequency of its use by any single surgeon or institution., Methods: The Nationwide Inpatient Sample data set was queried for all patient encounters involving a LD myocutaneous flap procedure. The study population was further restricted to female patients with a history of breast cancer or previous mastectomy. Demographics, Charlson Comorbidity Index scores, previous radiation history, and additional simultaneous procedures were extracted. Analysis was performed using nonparametric correlation coefficients and linear regression models., Results: In total, 2304 LD breast reconstruction hospitalizations were identified between 2008 and 2010. Average patient age was 52.1 years, average hospital length of stay (LOS) was 2.8 days, bilateral latissimus reconstruction was performed in 252 (10.9%) patients, and 1414 patients (61.4%) were delayed reconstruction. Previous irradiation was present in 389 (16.9%) patients and was correlated with delayed reconstruction (P < 0.001).Younger age was associated with bilateral latissimus reconstructions (P < 0.05), contralateral free flap reconstruction (P < 0.0001), and combination with implants or tissue expanders (both P < 0.0001).After adjustment for age and Charlson Comorbidity Index, increased LOS was observed in patients undergoing contralateral free flap reconstruction (+1.29 days, P < 0.05) and immediate reconstruction (mastectomy, +0.39 days unilateral, P < 0.05; +0.64 days, bilateral, P < 0.001). The use of tissue expanders and implants were found to decrease hospital LOS (bilateral implant, -0.65 days, P < 0.001; bilateral expander, -0.72 days, P < 0.001), likely from confounding comorbidities. Charlson Comorbidity Index was strongly related to LOS (+0.08 days per point, P < 0.005), whereas age was not statistically significant when considered with comorbidity., Conclusions: The LD is most commonly used for delayed or salvage breast reconstruction, with particular utility in irradiated patients. Younger patients tend to undergo more involved LD variants with bilateral reconstructions and expanders or implants. After adjusting for comorbidity, age and the use of bilateral latissimus flaps with implants or expanders have no adverse impact on LOS.

Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD., Competing Interests: The authors declare no conflict of interest.

Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

Abnormalities in the movement-related activation of the primary motor cortex (M1) are thought to be a major contributor to the motor signs of Parkinson's disease. The existing evidence, however, variably indicates that M1 is under-activated with movement, overactivated (due to a loss of functional specificity) or activated with abnormal timing. In addition, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those gaps in knowledge were addressed by studying the extracellular activity of antidromically-identified lamina 5b pyramidal-tract type neurons (n = 153) and intratelencephalic-type corticostriatal neurons (n = 126) in the M1 of two monkeys as they performed a step-tracking arm movement task. We compared movement-related discharge before and after the induction of parkinsonism by administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and quantified the spike rate encoding of specific kinematic parameters of movement using a generalized linear model. The fraction of M1 neurons with movement-related activity declined following MPTP but only marginally. The strength of neuronal encoding of parameters of movement was reduced markedly (mean 29% reduction in the coefficients from the generalized linear model). This relative decoupling of M1 activity from kinematics was attributable to reductions in the coefficients that estimated the spike rate encoding of movement direction (-22%), speed (-40%), acceleration (-49%) and hand position (-33%). After controlling for MPTP-induced changes in motor performance, M1 activity related to movement itself was reduced markedly (mean 36% hypoactivation). This reduced activation was strong in pyramidal tract-type neurons (-50%) but essentially absent in corticostriatal neurons. The timing of M1 activation was also abnormal, with earlier onset times, prolonged response durations, and a 43% reduction in the prevalence of movement-related changes beginning in the 150-ms period that immediately preceded movement. Overall, the results are consistent with proposals that under-activation and abnormal timing of movement-related activity in M1 contribute to parkinsonian motor signs but are not consistent with the idea that a loss of functional specificity plays an important role. Given that pyramidal tract-type neurons form the primary efferent pathway that conveys motor commands to the spinal cord, the dysfunction of movement-related activity in pyramidal tract-type neurons is likely to be a central factor in the pathophysiology of parkinsonian motor signs., (© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Importance: The revival of stereotactic surgery for Parkinson disease (PD) in the 1990s, with pallidotomy and then with high-frequency deep brain stimulation (DBS), has led to a renaissance in functional surgery for movement and other neuropsychiatric disorders., Objective: To examine the scientific foundations and rationale for the use of ablation and DBS for treatment of neurologic and psychiatric diseases, using PD as the primary example., Evidence Review: A summary of the large body of relevant literature is presented on anatomy, physiology, pathophysiology, and functional surgery for PD and other basal ganglia disorders., Findings: The signs and symptoms of movement disorders appear to result largely from signature abnormalities in one of several parallel and largely segregated basal ganglia thalamocortical circuits (ie, the motor circuit). The available evidence suggests that the varied movement disorders resulting from dysfunction of this circuit result from propagated disruption of downstream network activity in the thalamus, cortex, and brainstem. Ablation and DBS act to free downstream networks to function more normally. The basal ganglia thalamocortical circuit may play a key role in the expression of disordered movement, and the basal ganglia-brainstem projections may play roles in akinesia and disturbances of gait. Efforts are under way to target circuit dysfunction in brain areas outside of the traditionally implicated basal ganglia thalamocortical system, in particular, the pedunculopontine nucleus, to address gait disorders that respond poorly to levodopa and conventional DBS targets., Conclusions and Relevance: Deep brain stimulation is now the treatment of choice for many patients with advanced PD and other movement disorders. The success of DBS and other forms of neuromodulation for neuropsychiatric disorders is the result of the ability to modulate circuit activity in discrete functional domains within the basal ganglia circuitry with highly focused interventions, which spare uninvolved areas that are often disrupted with drugs.