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1.
J Craniofac Surg ; 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38330457

ABSTRACT

OBJECTIVE: Three-dimensional (3D) modeling technology aids the reconstructive surgeon in designing and tailoring individualized implants for the reconstruction of complex craniofacial fractures. Three-dimensional modeling and printing have traditionally been outsourced to commercial vendors but can now be incorporated into both private and academic craniomaxillofacial practices. The goal of this report is to present a low-cost, standardized office-based workflow for restoring bony orbital volume in traumatic orbital fractures. METHODS: Patients with internal orbital fractures requiring open repair were identified. After the virtual 3D models were created by iPlan 3.0 Cranial CMF software (Brainlab), the models were printed using an office-based 3D printer to shape and modify orbital plates to correctly fit the fracture defect. The accuracy of the anatomic reduction and the restored bony orbital volume measurements were determined using postoperative computed tomography images and iPlan software. RESULTS: Nine patients fulfilled the inclusion criteria: 8 patients had unilateral fractures and 1 patient had bilateral fractures. Average image processing and print time were 1.5 hours and 3 hours, respectively. The cost of the 3D printer was $2500 and the average material cost to print a single orbital model was $2. When compared with the uninjured side, the mean preoperative orbital volume increase and percent difference were 2.7 ± 1.3 mL and 10.9 ± 5.3%, respectively. Postoperative absolute volume and percent volume difference between the orbits were -0.2 ± 0.4 mL and -0.8 ± 1.7%, respectively. CONCLUSIONS: Office-based 3D printing can be routinely used in the repair of internal orbital fractures in an efficient and cost-effective manner to design the implant with satisfactory patient outcomes.

2.
J Craniofac Surg ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38534175

ABSTRACT

Traumatic optic neuropathy (TON) is a rare but potentially devastating complication of craniofacial trauma. Approximately half of patients with TON sustain permanent vision loss. In this study, we sought to identify the most common fracture patterns associated with TON. We performed a retrospective review of craniomaxillofacial CT scans of trauma patients who presented to the R Adams Cowley Shock Trauma Center from 2015 to 2017. Included were adult patients who had orbital fractures with or without other facial fractures. Patients diagnosed with TON by a formal ophthalmologic examination were analyzed. Craniofacial fracture patterns were identified. Bivariate analysis and multivariate logistic regression were performed to identify craniofacial fracture patterns most commonly associated with TON. A total of 574 patients with orbital fractures who met inclusion criteria [15 (2.6%)] were diagnosed with TON. The median [interquartile range (IQR)] age was 44 (28-59) years. Patients with optic canal fractures and sphenoid sinus fractures had greater odds of TON compared with patients who did not have these fracture types [adjusted odds ratio (aOR) 95% confidence interval (CI) 31.8 (2.6->100), 8.1 (2.7-24.4), respectively]. Patients who sustain optic canal and sphenoid sinus fractures in the setting of blunt facial trauma are at increased odds of having a TON. Surgeons and other physicians involved in the care of these patients should be aware of this association.

3.
J Craniofac Surg ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38534184

ABSTRACT

Fracture characteristics and postoperative outcomes of patients presenting with orbital fractures in Baltimore remain poorly investigated. The purpose of our study was to determine the fracture patterns, etiologies, and postoperative outcomes of patients treated for orbital fractures at 2 level I trauma centers in Baltimore. A retrospective cohort study was conducted on patients who underwent orbital fracture repair at the R Adams Cowley Shock Trauma Center and the Johns Hopkins Hospital from January 2015 to December 2019. Of 374 patients, 179 (47.9%) had orbital fractures due to violent trauma, 252 (67.4%) had moderate to near-total orbital fractures, 345 (92.2%) had orbital floor involvement, and 338 (90.4%) had concomitant neurological symptoms/signs. Almost half of the patients had at least one postoperative ocular symptom/sign [n = 163/333 (48.9%)]. Patients who had orbital fractures due to violent trauma were more likely to develop postoperative ocular symptoms/signs compared with those who had orbital fractures due to nonviolent trauma [n = 88/154 (57.1%), n = 75/179 (41.9%); P = 0.006]. After controlling for factors pertaining to injury severity, there was no significant difference in patient throughput or incidence of any postoperative ocular symptom/sign after repair between the two centers. Timely management of patients with orbital fractures due to violent trauma is crucial to mitigate the risk of postoperative ocular symptoms/signs.

4.
Ann Plast Surg ; 91(3): 326-330, 2023 09 01.
Article in English | MEDLINE | ID: mdl-37405878

ABSTRACT

BACKGROUND: Increased representation from both women and non-White ethnicities remains a topic of discussion in plastic surgery. Speakers at academic conferences are a form of visual representation of diversity within the field. This study determined the current demographic landscape of aesthetic plastic surgery and evaluated whether underrepresented populations receive equal opportunities to be invited speakers at The Aesthetic Society meetings. METHODS: Invited speaker's names, roles, and allotted time for presentation were extracted from the 2017 to 2021 meeting programs. Perceived gender and ethnicity were determined by visual analysis of photographs, whereas parameters of academic productivity and professorship were collected from Doximity, LinkedIn, Scopus, and institutional profiles. Differences in opportunities to present and academic credentials were compared between groups. RESULTS: Of the 1447 invited speakers between 2017 and 2021, 20% (n = 294) were women and 23% (n = 316) belonged to a non-White ethnicity. Representation from women significantly increased between 2017 and 2021 (14% vs 30%, P < 0.001), whereas the proportion of non-White speakers did not (25% vs 25%, P > 0.050) despite comparable h-indexes (15.3 vs 17.2) and publications (54.9 vs 75.9) to White speakers. Non-White speakers oftentimes had more academic titles, significant in 2019 ( P < 0.020). CONCLUSIONS: The proportion of female invited speakers has increased, with room for further improvement. Representation from non-White speakers has not changed. However, significantly more non-White speakers holding assistant professor titles may indicate increased ethnicity diversity in years to come. Future efforts should focus on improving diversity in positions of leadership while promoting functions that target young minority career individuals.


Subject(s)
Physicians, Women , Surgery, Plastic , Humans , Female , Male , Societies, Medical , Bibliometrics , Efficiency
5.
J Hand Surg Am ; 48(2): 109-116, 2023 02.
Article in English | MEDLINE | ID: mdl-35927123

ABSTRACT

PURPOSE: The Coronavirus disease 2019 pandemic occurred during the interview period for numerous surgical fellowships, resulting in most programs transitioning to a virtual interview format during the 2020-2021 application cycle. This study investigated modifications adopted by fellowship programs and perceptions of the virtual interview format among hand surgery fellowship applicants. METHODS: Voluntary, anonymous online surveys were emailed to all applicants to the Johns Hopkins hand surgery fellowship during the 2020-2021 interview cycle. The surveys were released after the rank order list certification deadline on May 6, 2021, and closed on May 18, 2021, before the match results were released. Descriptive statistics based on the overall cohort and primary outcome of an applicant's willingness to recommend virtual interviews in the future were conducted. RESULTS: Thirty-four of 112 (30.4%) applicants completed their surveys. Twenty-seven (79.4%) survey respondents recommended the virtual interview format in the future and 7 (20.6%) did not. Applicants who recommended virtual interviews were similar to those who did not on the basis of the number of interviews received and taken, information provided by programs, and self-rated competency with the virtual interview format. Those who recommended virtual interviews rated the effectiveness of self-advocacy higher compared with those who did not. All respondents agreed that cost savings and scheduling were more effective with virtual interviews. Perceived weaknesses differed between the 2 groups and included the lack of physical tour, difficulty with self-advocacy, and technical difficulties. The majority of survey respondents preferred in-person interviews before the interview cycle (n = 32, 94.1%), whereas nearly half of survey respondents preferred virtual interviews after the interview cycle (n = 16, 47.1%). CONCLUSIONS: Nearly 80% of survey respondents recommended virtual interviews in the future. Major benefits included effectiveness of scheduling and cost savings. CLINICAL RELEVANCE: Virtual interviews may be considered as an alternative or adjunct to in-person hand surgery fellowship interviews in the future.


Subject(s)
COVID-19 , Internship and Residency , Humans , COVID-19/epidemiology , Fellowships and Scholarships , Hand/surgery , Certification , Perception , Surveys and Questionnaires
6.
Proc Natl Acad Sci U S A ; 116(12): 5550-5557, 2019 03 19.
Article in English | MEDLINE | ID: mdl-30819883

ABSTRACT

The Hedgehog-signaling pathway is an important target in cancer research and regenerative medicine; yet, on the cellular level, many steps are still poorly understood. Extensive studies of the bulk behavior of the key proteins in the pathway established that during signal transduction they dynamically localize in primary cilia, antenna-like solitary organelles present on most cells. The secreted Hedgehog ligand Sonic Hedgehog (SHH) binds to its receptor Patched1 (PTCH1) in primary cilia, causing its inactivation and delocalization from cilia. At the same time, the transmembrane protein Smoothened (SMO) is released of its inhibition by PTCH1 and accumulates in cilia. We used advanced, single molecule-based microscopy to investigate these processes in live cells. As previously observed for SMO, PTCH1 molecules in cilia predominantly move by diffusion and less frequently by directional transport, and spend a fraction of time confined. After treatment with SHH we observed two major changes in the motional dynamics of PTCH1 in cilia. First, PTCH1 molecules spend more time as confined, and less time freely diffusing. This result could be mimicked by a depletion of cholesterol from cells. Second, after treatment with SHH, but not after cholesterol depletion, the molecules that remain in the diffusive state showed a significant increase in the diffusion coefficient. Therefore, PTCH1 inactivation by SHH changes the diffusive motion of PTCH1, possibly by modifying the membrane microenvironment in which PTCH1 resides.


Subject(s)
Cholesterol/metabolism , Cilia/metabolism , Hedgehog Proteins/metabolism , Patched-1 Receptor/metabolism , Animals , Cell Tracking , Mice , Signal Transduction , Smoothened Receptor/metabolism
7.
Ann Plast Surg ; 89(5): 552-559, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36279582

ABSTRACT

PURPOSE: The 2020-2021 interview cycle for integrated plastic surgery applicants was the first to be held virtually because of the COVID-19 pandemic. Here, we detail the largest study on integrated plastic surgery applicant perceptions after the virtual interview cycle. METHODS: A 35-question institutional review board-approved survey was distributed to medical students who had applied to the Johns Hopkins/University of Maryland or University of California San Diego integrated residency programs during the 2020-2021 interview cycle. Survey questions assessed the structure, strengths, and weaknesses of the exclusively virtual interview process. Survey administration and data collection were performed using the Qualtrics platform. RESULTS: Of 318 distributed surveys, 94 were completed. In addition, 91.5% of respondents preferred in-person interviews before the interview season, whereas 54.3% preferred in-person interviews afterward. Applicants who favored virtual interviews did not view being unable to physically meet with program staff as a detriment (P = .001) and felt they could effectively advocate for themselves (P = .002). Overall, the most cited strengths were the ability to complete more interviews (P = .01) and cost benefits (P = .02). Criticisms were directed at the impersonal nature of the exchange (86.2%), lack of physical tour (56.4%), and difficulties at self-advocacy (52.1%). CONCLUSION: Preference for virtual interviews increased from 7.5% to 34.0% after the virtual interview cycle. For several students, the ideal interview structure permits both in-person and virtual interviews to maximize flexibility. Augmenting with virtual city tours and one-on-one interviews may mitigate the impersonal nature of virtual interviews as perceived by some applicants.


Subject(s)
COVID-19 , Internship and Residency , Students, Medical , Surgery, Plastic , Humans , Surgery, Plastic/education , Pandemics , Surveys and Questionnaires
8.
J Craniofac Surg ; 33(4): 1046-1050, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-34873101

ABSTRACT

BACKGROUND: Although blunt cerebrovascular injury (BCVI) is recognized as a risk factor for trauma morbidity and mortality, little is described regarding similar cerebrovascular injury (CVI) in patients with penetrating wounds. The authors aim to characterize these injuries in the craniofacial self-inflicted gunshot wound (SIGSW) population. METHODS: An institutional review board (IRB)-approved retrospective nstudy was conducted on patients presenting to the R Adams Cowley Shock Trauma Center with SIGSWs between 2007 and 2016. All CVIs were categorized by location, type, and associated neurologic deficits. Demographic data, patient characteristics, additional studies, and long-term outcomes were collected. A multivariate analysis determining independent predictors of CVI in the SIGSW population was performed. RESULTS: Of the 73 patients with SIGSWs, 5 (6.8%) had CVIs separate from the bullet/cavitation tract (distant CVIs) and 9 had CVIs along the bullet/cavitation tract (in-tract CVIs). A total of 55.6% of in-tract and 40% of distant injuries were missed on initial radiology read. One distant CVI patient suffered a stroke during admission. The anterior to posterior gunshot wound trajectory was positively associated with distant CVIs when compared with no CVIs ( P  = 0.01). Vessel dissection was more prevalent in patients with distant CVIs, when compared against patients with in-tract CVIs ( P  = 0.02). CONCLUSIONS: Nearly 20% of craniofacial SIGSW patients have CVIs and 6.8% have BCVI-like injuries, which is 2-to-6-fold times higher than traditional BCVIs. Craniofacial SIGSWs serve as an independent screening criterion with comparable screening yields; the authors recommend radiographic screening for these patients with particular scrutiny for CVIs as they are frequently missed on initial radiographic interpretations.


Subject(s)
Cerebrovascular Trauma , Self Mutilation , Wounds, Gunshot , Wounds, Nonpenetrating , Cerebrovascular Trauma/epidemiology , Humans , Retrospective Studies , Trauma Centers , Wounds, Gunshot/diagnostic imaging , Wounds, Gunshot/epidemiology
9.
J Craniofac Surg ; 33(4): 1037-1041, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-34690316

ABSTRACT

INTRODUCTION: Achieving anatomic reduction and re-establishing premorbid occlusion in patients with complex maxillomandibular fractures is challenging even for seasoned surgeons. Historically, surgeons have utilized occlusal splints to help establish occlusal relationships before fracture reduction and fixation. These acrylic splints are fabricated from dental impressions and require manual repositioning of tooth bearing segments along the fracture line to reapproximate premorbid occlusion. The process is laborious, requires a dental lab, and is less efficacious in edentulous patients or those with significantly comminuted fractures; as such it has largely fallen out of practice. Recently, with advances in virtual 3D modeling and printing, we demonstrate that occlusal splints can be designed from computed tomography scans, manipulated virtually, and printed without obtaining impressions from the patient. METHODS/RESULTS: In our series of 3 patients with complex maxillomandibular fractures, occlusal splints were created by 1) obtaining maxillofacial computed tomography scans, 2) reducing the fractures virtually, and 3) using orthognathic virtual surgery software to create the splint. The time between planning and delivery of the splint was 4 to 7 days. These splints were successfully utilized to help establish premorbid occlusion in conjunction with maxillomandibular fixation and aided in expeditious intraoperative fracture reduction and fixation. CONCLUSIONS: In the treatment of complex facial fractures, occlusal splints can be a useful adjunct in the operative reduction and fixation of fractures. With the advent of virtual preoperative surgical planning via 3D modeling and 3D printing, these occlusal splints can be created of a sufficient fidelity to avoid the strict need for dental impressions.


Subject(s)
Orthognathic Surgical Procedures , Surgery, Computer-Assisted , Humans , Jaw Fixation Techniques , Occlusal Splints , Orthognathic Surgical Procedures/methods , Printing, Three-Dimensional , Splints , Surgery, Computer-Assisted/methods
10.
J Craniofac Surg ; 33(8): 2379-2382, 2022.
Article in English | MEDLINE | ID: mdl-35864582

ABSTRACT

INTRODUCTION: The 2021 interview cycle for craniofacial fellowship applicants was the first to be held virtually due to the coronavirus disease 2019 pandemic. Here, we detail the craniofacial fellowship applicant perceptions and experience on the virtual interview process. MATERIALS AND METHODS: An institutional review board-approved 35-question survey study on the perception of the virtual interview process among craniofacial fellowship applicants was conducted. Surveys were distributed to individuals who had applied through the match, overseen by the American Society of Craniofacial Surgeons (ASCFS). RESULTS: Ten surveys were fully completed with a corresponding response rate of 48%. The average number of interviews completed was 12.7±7.7 and 50% of applicants interviewed at >1 program in a single day. Overall, 90% of respondents preferred in-person interviews before the interview season, however, only 10% preferred the in-person format afterwards. Preference for a virtual-only format increased from 10% to 70%. Applicants cited cost (100%), ease of scheduling (90%), and ability to participate in more interviews (70%) as the primary strengths of the virtual platform; none reported difficulties with self-advocacy. After the interview cycle, 90% stated they would recommend virtual interviews. CONCLUSIONS: The greatest strengths of virtual interviews were the ability to participate in more interviews, the ease of scheduling, and the cost benefits. Most applicants reported the same or increased ability for self-advocacy with virtual interviews. Following the index interview cycle for 2021, the majority of fellowship applicants now appear to prefer a virtual-only or hybrid format and would recommend virtual interviews in the future.


Subject(s)
COVID-19 , Internship and Residency , Surgeons , Humans , Fellowships and Scholarships , COVID-19/epidemiology , Pandemics , Surveys and Questionnaires
11.
Cleft Palate Craniofac J ; : 10556656221145079, 2022 Dec 21.
Article in English | MEDLINE | ID: mdl-36542329

ABSTRACT

OBJECTIVE: The present study aimed to investigate the risk factors, complication profiles, and clinical outcomes of cleft and noncleft patients undergoing single jaw (mandibular or LeFort 1) and bimaxillary (BSSO + LeFort 1). DESIGN: Retrospective Cross-sectional Study Setting: National Surgical Quality Improvement Program database 2018-2019. PATIENTS: Pediatric patients. INTERVENTIONS: Outcomes for mandibular, LeFort 1, and bimaxillary osteotomy were retrospectively evaluated for cleft and noncleft patients. MAIN OUTCOME MEASURES: Multivariate logistic regression was used to determine the odds of complications and length of stay for cleft and noncleft patients undergoing single jaw and double jaw surgery. RESULTS: 669 pediatric patient underwent orthognathic surgery in the study period; the majority received LF1 only (n = 385; 58.3%), followed by mandible only (n = 179; 27.1%), and bimaxillary (n = 105; 15.9%%). Cleft differences were present in 56% of LFI patients, 32% of mandibular patients, and 22% of bimaxillary patients. After multivariate adjustment, ASA class III was associated with nearly 400% increased odds of any complication including readmission and reoperation (OR = 5.99; CI [[1.54-23.32]], p < 0.01, and 65% increased LOS (ß-coefficient = 1.65, CI [1.37-1.99], p < 0.01). Presence of cleft was not significantly associated with odds of any complication (p = 0.69) nor increased LOS (p = 0.46) in this population. CONCLUSION: Complications remained low between surgery types among cleft and noncleft patients. The most significant risk factor in pediatric orthognathic surgery was not the presence of cleft but rather increased ASA class. Though common in patients seeking orthognathic surgery, cleft differences did not cause additional risk after adjustment for other variables.

12.
J Craniofac Surg ; 32(6): 2064-2067, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-33770041

ABSTRACT

INTRODUCTION: Self-inflicted gunshot wounds to the face frequently result in devastating injuries; however, there is a paucity of large experiences describing determinants of mortality and outcomes. METHODS: Using the National Trauma Databank from 2007 to 2015, patients suffering self-inflicted firearm facial injuries were included. RESULTS: Over 9 years 7869 patients were included: 87.7% were male, 46.4% suffered traumatic brain injury (TBI) and overall in-hospital mortality was 44.7%. The majority (67.8%) of in-hospital mortality occurred within the first 24 hours. Using multiple regression, advanced age (>65 years), presence of TBI, admission hypotension, and decreased Glasgow coma score were each independently associated with increased odds of mortality (all P < 0.001). Mandible or combined mandible/midface fracture injury patterns were most likely to survive (P < 0.001). Of those surviving to hospital discharge, the median [interquartile range] length of stay was 13 [6, 23] days, 86.6% required an intensive care unit stay with 67% requiring intubation and 42.5% tracheostomy. Among survivors, the combined mandible and midface fracture pattern resulted in the highest rates of tracheostomy (70.5%), gastrostomy tube placement (50.5%), and facial operations (87.0%) with a median [interquartile range] of 5 [3, 7] operative trips (all P < 0.001). CONCLUSIONS: Self-inflicted facial firearm injuries are highly morbid injuries with the majority of in-hospital deaths occurring the first hospital day. Differences including concomitant TBI, facial injury pattern, neurologic status, and presence of hypotension on admission were independently associated with survival/death. More extensive facial injuries (combined mandible and midface fracture patterns) were more likely to survive and required more intensive interventions.


Subject(s)
Facial Injuries , Firearms , Wounds, Gunshot , Aged , Databases, Factual , Facial Injuries/epidemiology , Facial Injuries/etiology , Hospital Mortality , Humans , Male , Retrospective Studies , Trauma Centers , Wounds, Gunshot/epidemiology
13.
J Craniofac Surg ; 32(8): 2741-2743, 2021.
Article in English | MEDLINE | ID: mdl-34238878

ABSTRACT

BACKGROUND: Prominent ears affect up to 5% of the population and can lead to social and psychological concerns at a critical time of social development. It can be addressed with an otoplasty, which is often considered a cosmetic procedure. The authors assessed insurance coverage of all indications of otoplasty and their medical necessity criteria. METHODS: A cross-sectional analysis was conducted of 58 insurance policies for otoplasty. The insurance companies were selected based on their state enrolment and market share. A web-based search and telephone interviews were utilized to identify the policies. Medically necessary criteria were then abstracted from the publicly available policies. RESULTS: Of the 58 insurance policies assessed, 25 (43%) provide coverage of otoplasty. There were 2 indications for coverage: hearing loss (n = 20, 80%) and normal approximation (n = 14, 56%), which would encompass prominent ears. Normal approximation was a covered indication for significantly fewer insurers than hearing loss (56% versus 80%, P = 0.0013). Of all the otoplasty policies which covered normal approximation, 21% (n = 3) addressed protruding ears as an etiology. Prominent ears were not included in any policies which covered hearing loss. All policies inclusive of prominent ears required a protrusion of >20 mm from the temporal surface of the head (n = 3, 100%). CONCLUSIONS: There is a great discrepancy in insurance coverage of otoplasty. A greater proportion of policies cover hearing loss compared to normal approximation. The authors encourage plastic surgeons to advocate for the necessity and coverage of normal approximation by insurers.


Subject(s)
Insurance Coverage , Plastic Surgery Procedures , Cross-Sectional Studies , Face , Humans , United States
14.
Microsurgery ; 40(6): 710-716, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32277511

ABSTRACT

BACKGROUND: The sural nerve is the most frequently harvested nerve autograft and is most often biopsied in the workup of peripheral neuropathy. While the complication types associated with these two procedures are well known, their clinical significance is poorly understood and there is a paucity of data regarding the complication rates. METHODS: Pubmed search identified studies regarding complications after sural nerve harvest and biopsy. The data was grouped into sensory deficits, chronic pain, sensory symptoms, wound infections, wound complications, other postoperative complications, and complications impacting daily life. The incidence of each complication was calculated, and a chi-square analysis was performed to determine if there were any differences between nerve biopsies and graft harvest with respect to each complication. RESULTS: Twelve studies yielded 478 sural nerve procedures. Sensory deficits occurred at a rate of 92.9%, chronic pain at 19.7%, sensory symptoms at 41.1%, wound infections at 5.7%, noninfectious wound complications at 7.8%, and impact on daily life at 5.0%. The differences in wound infections, sensory symptoms, and impact on daily life between biopsies versus graft excisions were found to reach statistical significance (p < .05). CONCLUSIONS: Sural nerve excisions can cause chronic postoperative donor-site complications. Given these complications, alternative available mediums for nerve reconstruction should be explored and utilized wherever appropriate. If an alternative medium is unavailable and nerve autograft must be harvested for nerve reconstruction, then patients should be counseled about risks for developing donor site complications that may negatively affect quality of life.


Subject(s)
Quality of Life , Sural Nerve , Autografts , Biopsy/adverse effects , Humans , Morbidity , Postoperative Complications/epidemiology , Postoperative Complications/etiology
15.
Biophys J ; 116(2): 319-329, 2019 01 22.
Article in English | MEDLINE | ID: mdl-30598282

ABSTRACT

Super-resolution (SR) microscopy has been used to observe structural details beyond the diffraction limit of ∼250 nm in a variety of biological and materials systems. By combining this imaging technique with both computer-vision algorithms and topological methods, we reveal and quantify the nanoscale morphology of the primary cilium, a tiny tubular cellular structure (∼2-6 µm long and 200-300 nm in diameter). The cilium in mammalian cells protrudes out of the plasma membrane and is important in many signaling processes related to cellular differentiation and disease. After tagging individual ciliary transmembrane proteins, specifically Smoothened, with single fluorescent labels in fixed cells, we use three-dimensional (3D) single-molecule SR microscopy to determine their positions with a precision of 10-25 nm. We gain a dense, pointillistic reconstruction of the surfaces of many cilia, revealing large heterogeneity in membrane shape. A Poisson surface reconstruction algorithm generates a fine surface mesh, allowing us to characterize the presence of deformations by quantifying the surface curvature. Upon impairment of intracellular cargo transport machinery by genetic knockout or small-molecule treatment of cells, our quantitative curvature analysis shows significant morphological differences not visible by conventional fluorescence microscopy techniques. Furthermore, using a complementary SR technique, two-color, two-dimensional stimulated emission depletion microscopy, we find that the cytoskeleton in the cilium, the axoneme, also exhibits abnormal morphology in the mutant cells, similar to our 3D results on the Smoothened-measured ciliary surface. Our work combines 3D SR microscopy and computational tools to quantitatively characterize morphological changes of the primary cilium under different treatments and uses stimulated emission depletion to discover correlated changes in the underlying structure. This approach can be useful for studying other biological or nanoscale structures of interest.


Subject(s)
Cilia/ultrastructure , Single Molecule Imaging/methods , Animals , Axoneme/ultrastructure , Cell Membrane/ultrastructure , Cells, Cultured , Fluorescent Dyes/chemistry , Membrane Proteins/chemistry , Mice , Microscopy, Fluorescence/methods
16.
Ann Plast Surg ; 82(6): 653-660, 2019 06.
Article in English | MEDLINE | ID: mdl-30648997

ABSTRACT

PURPOSE: The investigators wanted to evaluate, analyze, and compare the current microsurgical repair modalities (primary repair, autograft, tube conduit, and allograft reconstruction) in achieving functional sensory recovery in inferior alveolar and lingual nerve reconstructions due to injury. METHODS: A literature review was undertaken to identify studies focusing on microsurgical repair of inferior alveolar and lingual nerve injuries. Included studies provided a defined sample size, the reconstruction modality, and functional sensory recovery rates. A Fischer exact test analysis was performed with groups based on the nerve and repair type, which included subgroups of specific nerve gap reconstruction modalities. RESULTS: Twelve studies were analyzed resulting in a sample consisting of 122 lingual nerve and 137 inferior alveolar nerve reconstructions. Among the nerve gap reconstructions for the lingual nerve, processed nerve allografts and autografts were found to be superior in achieving functional sensory recovery over the conduits with P values of 0.0001 and 0.0003, respectively. Among the nerve gap reconstructions for the inferior alveolar nerve, processed nerve allografts and autografts were also found to be superior in achieving functional sensory recovery over the conduits with P values of 0.027 and 0.026, respectively. Overall, nerve gap reconstructions with allografts and autografts for inferior alveolar and lingual nerve reconstruction were superior in achieving functional sensory recovery with a P value of <0.0001. CONCLUSIONS: The data analyzed in this study suggest that primary tension-free repair should be performed in inferior alveolar and lingual nerve reconstructions when possible. If a bridging material is to be used, then processed nerve allografts and autografts are both superior to conduits and noninferior to each other. In addition, allografts do not have the complications related to autograft harvesting such as permanent donor site morbidity. Based on the conclusions drawn from these data, we provide a reproducible operative technique for inferior alveolar and lingual nerve reconstruction.


Subject(s)
Lingual Nerve Injuries/surgery , Mandibular Nerve/surgery , Microsurgery/methods , Oral Surgical Procedures/adverse effects , Peripheral Nerve Injuries/surgery , Plastic Surgery Procedures/methods , Dentistry, Operative , Evidence-Based Medicine , Female , Humans , Lingual Nerve Injuries/etiology , Male , Mandibular Nerve/pathology , Neurosurgical Procedures/methods , Oral Surgical Procedures/methods , Peripheral Nerve Injuries/etiology , Postoperative Complications/physiopathology , Postoperative Complications/surgery , Recovery of Function/physiology , Transplantation, Autologous , Treatment Outcome
17.
Proc Natl Acad Sci U S A ; 112(27): 8320-5, 2015 Jul 07.
Article in English | MEDLINE | ID: mdl-26100903

ABSTRACT

Accumulation of the signaling protein Smoothened (Smo) in the membrane of primary cilia is an essential step in Hedgehog (Hh) signal transduction, yet the molecular mechanisms of Smo movement and localization are poorly understood. Using ultrasensitive single-molecule tracking with high spatial/temporal precision (30 nm/10 ms), we discovered that binding events disrupt the primarily diffusive movement of Smo in cilia at an array of sites near the base. The affinity of Smo for these binding sites was modulated by the Hh pathway activation state. Activation, by either a ligand or genetic loss of the negatively acting Hh receptor Patched-1 (Ptch), reduced the affinity and frequency of Smo binding at the base. Our findings quantify activation-dependent changes in Smo dynamics in cilia and highlight a previously unknown step in Hh pathway activation.


Subject(s)
Cilia/metabolism , Hedgehog Proteins/metabolism , Receptors, Cell Surface/metabolism , Receptors, G-Protein-Coupled/metabolism , Algorithms , Animals , Cell Tracking/methods , Cells, Cultured , Embryo, Mammalian/cytology , Fibroblasts/metabolism , Hedgehog Proteins/genetics , Kinetics , Mice, Knockout , Mice, Transgenic , Microscopy, Confocal , Patched Receptors , Patched-1 Receptor , Protein Binding , Receptors, Cell Surface/genetics , Receptors, G-Protein-Coupled/genetics , Signal Transduction , Smoothened Receptor
18.
TH Open ; 8(2): e216-e223, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38831793

ABSTRACT

Introduction/Objective Colonoscopy with polypectomy is an integral component of colorectal cancer screening. There are limited data and consensus on periprocedural anticoagulation management, especially regarding bleeding risk with uninterrupted anticoagulation and thromboembolic risk with interruption. Our aim was to determine the incidence of bleeding and thromboembolic complications among colon screening participants undergoing colonoscopy following implementation of a novel patient care pathway for standardized periprocedural anticoagulation management. Methods We conducted a retrospective study including all participants (age 50-74) on an oral anticoagulant (e.g., vitamin K antagonists, direct oral anticoagulants) referred to the British Columbia Colon Screening Program for colonoscopy following abnormal fecal immunochemical test in a 6-month period (March-August 2022). Data relating to their specific periprocedural anticoagulant management and colonoscopy results including method of polypectomy were obtained. Primary outcomes were major bleeding and arterial or venous thromboembolic events from time of oral anticoagulant interruption until 14 days of postcolonoscopy. Secondary outcomes included nonmajor and minor bleeding, acute coronary syndrome, emergency room visit, hospital admission, and death due to any cause. Results Over the 6-month period, 162 participants completed standardized periprocedural anticoagulation management, colonoscopy ± polypectomy, and 14-day follow-up. One (0.6%) had a major bleeding event and one (0.6%) had an arterial thromboembolic event. Conclusions A novel patient care pathway for standardized periprocedural anticoagulation management with a multidisciplinary team is associated with low rates of major bleeding and thrombotic complications after colonoscopy with polypectomy.

19.
Thromb Res ; 239: 109036, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38776611

ABSTRACT

Adherence to guideline recommendations for venous thromboembolism prophylaxis (VTE) in hospitalized medical patients is suboptimal despite national policies and institutional interventions. The aim of this quality improvement project was to improve adherence to guidelines and decrease the overuse of VTE prophylaxis in order to reduce the institutional cost for heparins. A multidisciplinary anticoagulation stewardship program (ACSP) using the audit and feedback strategy was implemented on the medicine inpatient units at a teaching hospital in Canada. The primary outcome measure was a comparison, pre and post introduction of the ACSP, of the costs per 6-month period for prophylactic dose enoxaparin and unfractionated heparin on the medicine units. The balancing measures were the 90-day VTE rate and major bleeding rate during the hospitalization. Six months after the implementation of the ACSP, the cost was decreased by >50 % without any observed negative impact on patient safety. This study demonstrates the potential for anticoagulation stewardship programs to optimize the use of VTE prophylaxis and reduce the associated costs and risks.


Subject(s)
Anticoagulants , Guideline Adherence , Hospitalization , Venous Thromboembolism , Humans , Venous Thromboembolism/prevention & control , Venous Thromboembolism/drug therapy , Venous Thromboembolism/economics , Anticoagulants/therapeutic use , Female , Male , Practice Guidelines as Topic , Middle Aged , Aged , Hemorrhage/chemically induced , Heparin/therapeutic use , Heparin/economics , Canada
20.
Sci Rep ; 14(1): 3654, 2024 02 13.
Article in English | MEDLINE | ID: mdl-38351033

ABSTRACT

Postoperative diplopia is the most common complication following orbital fracture repair (OFR). Existing evidence on its risk factors is based on single-institution studies and small sample sizes. Our study is the first multi-center study to develop and validate a risk calculator for the prediction of postoperative diplopia following OFR. We reviewed trauma patients who underwent OFR at two high-volume trauma centers (2015-2019). Excluded were patients < 18 years old and those with postoperative follow-up < 2 weeks. Our primary outcome was incidence/persistence of postoperative diplopia at ≥ 2 weeks. A risk model for the prediction of postoperative diplopia was derived using a development dataset (70% of population) and validated using a validation dataset (remaining 30%). The C-statistic and Hosmer-Lemeshow tests were used to assess the risk model accuracy. A total of n = 254 adults were analyzed. The factors that predicted postoperative diplopia were: age at injury, preoperative enophthalmos, fracture size/displacement, surgical timing, globe/soft tissue repair, and medial wall involvement. Our predictive model had excellent discrimination (C-statistic = 80.4%), calibration (P = 0.2), and validation (C-statistic = 80%). Our model rules out postoperative diplopia with a 100% sensitivity and negative predictive value (NPV) for a probability < 8.9%. Our predictive model rules out postoperative diplopia with an 87.9% sensitivity and a 95.8% NPV for a probability < 13.4%. We designed the first validated risk calculator that can be used as a powerful screening tool to rule out postoperative diplopia following OFR in adults.


Subject(s)
Enophthalmos , Orbital Fractures , Adult , Humans , Adolescent , Orbital Fractures/surgery , Orbital Fractures/complications , Diplopia/etiology , Retrospective Studies , Enophthalmos/complications , Risk Factors , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Treatment Outcome , Multicenter Studies as Topic
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