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1.
Nucleic Acids Res ; 51(17): 9397-9414, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37526268

RESUMEN

Ribosome biogenesis is one of the biggest consumers of cellular energy. More than 20 genetic diseases (ribosomopathies) and multiple cancers arise from defects in the production of the 40S (SSU) and 60S (LSU) ribosomal subunits. Defects in the production of either the SSU or LSU result in p53 induction through the accumulation of the 5S RNP, an LSU assembly intermediate. While the mechanism is understood for the LSU, it is still unclear how SSU production defects induce p53 through the 5S RNP since the production of the two subunits is believed to be uncoupled. Here, we examined the response to SSU production defects to understand how this leads to the activation of p53 via the 5S RNP. We found that p53 activation occurs rapidly after SSU production is blocked, prior to changes in mature ribosomal RNA (rRNA) levels but correlated with early, middle and late SSU pre-rRNA processing defects. Furthermore, both nucleolar/nuclear LSU maturation, in particular late stages in 5.8S rRNA processing, and pre-LSU export were affected by SSU production defects. We have therefore uncovered a novel connection between the SSU and LSU production pathways in human cells, which explains how p53 is induced in response to SSU production defects.


Asunto(s)
Subunidades Ribosómicas Grandes , Subunidades Ribosómicas Pequeñas , Proteína p53 Supresora de Tumor , Humanos , Proteínas Ribosómicas/genética , Proteínas Ribosómicas/metabolismo , Subunidades Ribosómicas Grandes/metabolismo , Subunidades Ribosómicas Pequeñas/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
2.
Stroke ; 55(1): 22-30, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38134268

RESUMEN

BACKGROUND: Cerebral cavernous malformation with symptomatic hemorrhage (SH) are targets for novel therapies. A multisite trial-readiness project (https://www.clinicaltrials.gov; Unique identifier: NCT03652181) aimed to identify clinical, imaging, and functional changes in these patients. METHODS: We enrolled adult cerebral cavernous malformation patients from 5 high-volume centers with SH within the prior year and no planned surgery. In addition to clinical and imaging review, we assessed baseline, 1- and 2-year National Institutes of Health Stroke Scale, modified Rankin Scale, European Quality of Life 5D-3 L, and patient-reported outcome-measurement information system, Version 2.0. SH and asymptomatic change rates were adjudicated. Changes in functional scores were assessed as a marker for hemorrhage. RESULTS: One hundred twenty-three, 102, and 69 patients completed baseline, 1- and 2-year clinical assessments, respectively. There were 21 SH during 178.3 patient years of follow-up (11.8% per patient year). At baseline, 62.6% and 95.1% of patients had a modified Rankin Scale score of 1 and National Institutes of Health Stroke Scale score of 0 to 4, respectively, which improved to 75.4% (P=0.03) and 100% (P=0.06) at 2 years. At baseline, 74.8% had at least one abnormal patient-reported outcome-measurement information system, Version 2.0 domain compared with 61.2% at 2 years (P=0.004). The most common abnormal European Quality of Life 5D-3 L domains were pain (48.7%), anxiety (41.5%), and participation in usual activities (41.4%). Patients with prospective SH were more likely than those without SH to display functional decline in sleep, fatigue, and social function patient-reported outcome-measurement information system, Version 2.0 domains at 2 years. Other score changes did not differ significantly between groups at 2 years. The sensitivity of scores as an SH marker remained poor at the time interval assessed. CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients. Functional outcomes and patient-reported outcomes generally improved over 2 years. No score change was highly sensitive or specific for SH and could not be used as a primary end point in a trial.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Accidente Cerebrovascular , Adulto , Humanos , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemorragia , Estudios Prospectivos , Calidad de Vida , Accidente Cerebrovascular/terapia , Resultado del Tratamiento
3.
Stroke ; 55(1): 31-39, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38134265

RESUMEN

BACKGROUND: Quantitative susceptibility mapping (QSM) and dynamic contrast-enhanced quantitative perfusion (DCEQP) magnetic resonance imaging sequences assessing iron deposition and vascular permeability were previously correlated with new hemorrhage in cerebral cavernous malformations. We assessed their prospective changes in a multisite trial-readiness project. METHODS: Patients with cavernous malformation and symptomatic hemorrhage (SH) in the prior year, without prior or planned lesion resection or irradiation were enrolled. Mean QSM and DCEQP of the SH lesion were acquired at baseline and at 1- and 2-year follow-ups. Sensitivity and specificity of biomarker changes were analyzed in relation to predefined criteria for recurrent SH or asymptomatic change. Sample size calculations for hypothesized therapeutic effects were conducted. RESULTS: We logged 143 QSM and 130 DCEQP paired annual assessments. Annual QSM change was greater in cases with SH than in cases without SH (P=0.019). Annual QSM increase by ≥6% occurred in 7 of 7 cases (100%) with recurrent SH and in 7 of 10 cases (70%) with asymptomatic change during the same epoch and 3.82× more frequently than clinical events. DCEQP change had lower sensitivity for SH and asymptomatic change than QSM change and greater variance. A trial with the smallest sample size would detect a 30% difference in QSM annual change during 2 years of follow-up in 34 or 42 subjects (1 and 2 tailed, respectively); power, 0.8, α=0.05. CONCLUSIONS: Assessment of QSM change is feasible and sensitive to recurrent bleeding in cavernous malformations. Evaluation of an intervention on QSM percent change may be used as a time-averaged difference between 2 arms using a repeated measures analysis. DCEQP change is associated with lesser sensitivity and higher variability than QSM. These results are the basis of an application for certification by the US Food and Drug Administration of QSM as a biomarker of drug effect on bleeding in cavernous malformations. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03652181.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Hemorragia , Humanos , Estudios Prospectivos , Hemorragia/etiología , Hemorragia/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/complicaciones , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Biomarcadores , Imagen por Resonancia Magnética/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/complicaciones
4.
Cell Commun Signal ; 22(1): 23, 2024 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-38195510

RESUMEN

Cerebral cavernous malformation (CCM) is a hemorrhagic neurovascular disease with no currently available therapeutics. Prior evidence suggests that different cell types may play a role in CCM pathogenesis. The contribution of each cell type to the dysfunctional cellular crosstalk remains unclear. Herein, RNA-seq was performed on fluorescence-activated cell sorted endothelial cells (ECs), pericytes, and neuroglia from CCM lesions and non-lesional brain tissue controls. Differentially Expressed Gene (DEG), pathway and Ligand-Receptor (LR) analyses were performed to characterize the dysfunctional genes of respective cell types within CCMs. Common DEGs among all three cell types were related to inflammation and endothelial-to-mesenchymal transition (EndMT). DEG and pathway analyses supported a role of lesional ECs in dysregulated angiogenesis and increased permeability. VEGFA was particularly upregulated in pericytes. Further pathway and LR analyses identified vascular endothelial growth factor A/ vascular endothelial growth factor receptor 2 signaling in lesional ECs and pericytes that would result in increased angiogenesis. Moreover, lesional pericytes and neuroglia predominantly showed DEGs and pathways mediating the immune response. Further analyses of cell specific gene alterations in CCM endorsed potential contribution to EndMT, coagulation, and a hypoxic microenvironment. Taken together, these findings motivate mechanistic hypotheses regarding non-endothelial contributions to lesion pathobiology and may lead to novel therapeutic targets. Video Abstract.


Asunto(s)
Hemangioma Cavernoso del Sistema Nervioso Central , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/genética , Hemangioma Cavernoso del Sistema Nervioso Central/genética , Células Endoteliales , Perfilación de la Expresión Génica , Transcriptoma , Microambiente Tumoral
5.
Aesthetic Plast Surg ; 48(4): 621-632, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37935961

RESUMEN

BACKGROUND: We designed a survey to evaluate preferences of facial appearance in transgender male (TM), transgender female (TF) and gender nonbinary patients to better inform goals of facial gender affirming surgery (FGAS) in gender nonbinary patients. METHODS: TM/TF and nonbinary patients > 18 years old were identified via retrospective chart review and distributed an anonymized survey via email from October 3 to December 31, 2022. To assess facial preferences, AI-generated and open-source portraits were edited to create five image sets with a range of features from masculine to feminine for the forehead, mandible/chin and hairline. Data were analyzed using Fisher's exact tests and ANOVA in R-Studio. RESULTS: Survey response rate was 32% (180 patients identified via chart review, 58 respondents; TM = 5, TF = 39, nonbinary = 14). TM and TF patients as well as TF and nonbinary patients had significantly different preferences for all regions (p < 0.005; all series), while TM and nonbinary patients did not (p => 0.05; all series). TF patients consistently selected 4s with neutral or more feminine features. TM and nonbinary patients, however, demonstrated no consistent preference for either male or female features but rather a range of responses spanning extremes of both masculine and feminine options. When stratified by sex assigned at birth, nonbinary patients consistently identified preferences opposite to their assigned gender. CONCLUSION: Gender nonbinary and TM patients appear to have uniquely individual preferences regarding facial appearance that do not fit into classically masculine or feminine patterns/phenotypes. As a result, we recommend individualized preoperative planning for FGAS to achieve the optimal result in these patient populations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Asunto(s)
Cirugía de Reasignación de Sexo , Personas Transgénero , Transexualidad , Recién Nacido , Humanos , Masculino , Femenino , Adolescente , Estudios Retrospectivos , Cara/cirugía , Cirugía de Reasignación de Sexo/métodos
6.
Aesthetic Plast Surg ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858245

RESUMEN

BACKGROUND: Facial feminization may be performed to alleviate gender dysphoria among transfeminine patients. The upper third of the face has several characteristics, including hairline shape and position, brow position, and forehead protrusion, that may confer feminine identity. The purpose of this study is to conduct a scoping literature review of techniques performed for forehead feminization and to additionally study clinical outcomes within an institutional cohort. METHODS: A systematic literature review was conducted to review articles that discussed techniques and clinical outcomes associated with procedures performed for feminization of the upper third of the face. A retrospective review of patients undergoing such procedures by the senior author was then conducted. Variables collected included demographic factors, operative details, and postoperative outcomes such as complications, revisions, and re-operations. RESULTS: Initial review yielded sixty-seven articles. Title and abstract review followed by standardized application of inclusion and exclusion criteria resulted in a total of twenty-two studies for analysis. Priorities of forehead feminization entail frontal bossing reduction, frontonasal angle widening, orbital contouring, brow lifting, and hairline advancement. Eighty-five patients were included for analysis. The majority were of Caucasian race (56%) and had type 3 forehead classification (92%). The average planned setback of the anterior table was 4.12 mm. CONCLUSIONS: The core tenets of the feminization of the forehead lie in the overall creation of a harmonic curvature of the forehead with other facial features. Our multi-pronged analysis presents an updated review of these principles, which may help plastic surgeons in performing procedures to feminize the upper third of the face. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266.

7.
Wilderness Environ Med ; 35(2): 147-154, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38465643

RESUMEN

INTRODUCTION: Suspension syndrome (SS) develops when venous blood pools in extremities of passively suspended individuals, resulting in presyncopal symptoms and potential unconsciousness or death independent of additional injuries. We investigated use of leg raising to delay onset of SS, as it can decrease venous pooling and increase cardiac return and systemic perfusion. METHODS: Participants were suspended in rock climbing harnesses at an indoor climbing wall in a legs-dangling control position or a legs-raised interventional position to compare physiological outcomes between groups. Participants were suspended for a maximum of 45 min. Onset of 2 or more symptoms of SS, such as vertigo, lightheadedness, or nausea, halted suspension immediately. We recorded each participant's heart rate, blood pressure, oxygen saturation, lower leg oxygen saturation, pain rating, and presyncope scores presuspension, midsuspension, and postsuspension, as well as total time suspended. RESULTS: There were 24 participants. There was a significant difference in total time suspended between groups (43.05±6.7 min vs 33.35±9.02 min, p=0.007). There was a significant difference in heart rate between groups overall (p=0.012), and between groups, specifically at the midsuspension time interval (80±11 bpm vs 100±17 bpm, p=0.003). Pain rating was significantly different between groups (p=0.05). Differences in blood pressure, oxygen saturation, lower leg oxygen saturation, and presyncope scores were not significant. CONCLUSION: Leg raising lengthened the time individuals tolerated passive suspension and delayed symptom onset.


Asunto(s)
Síncope , Humanos , Masculino , Adulto , Femenino , Síncope/etiología , Pierna/irrigación sanguínea , Montañismo , Frecuencia Cardíaca , Persona de Mediana Edad , Adulto Joven
8.
Ann Surg ; 277(5): e1184-e1190, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35786682

RESUMEN

OBJECTIVE: This study investigates the effect of gender-affirming facial feminization surgery (FFS) on psychosocial outcomes in patients with gender dysphoria. BACKGROUND: Comprehensive analyses of psychosocial outcomes after gender-affirming FFS are absent in the literature resulting in a paucity of information on the impact of FFS on quality of life as well as ramifications in health insurance coverage of FFS. METHODS: Scores from 11 validated, quantitative instruments from the Patient-Reported Outcomes Measurement Information System (PROMIS) assessing anxiety, anger, depression, global mental health, global physical health, satisfaction with sex life, positive affect, emotional support, social isolation, companionship, and meaning and purpose. Patients within the preoperative group (pre-FFS) were evaluated >30 days before surgery and patients within the postoperative group (post-FFS) were evaluated ≥10 weeks after surgery. RESULTS: A total of 169 patients [mean (SD) age, 33.5 (10.8) years] were included. Compared with the pre-FFS group (n=107), the post-FFS group (n=62) reported improved scores anxiety (56.8±8.8 vs 60.1±7.9, P =0.01), anger (47.4±7.6 vs 51.2±9.6, P =0.01), depression (52.2±9.2 vs 57.0±8.9, P =0.001), positive affect (46.6±8.9 vs 42.9±8.7, P =0.01), meaning and purpose (49.9±10.7 vs 46.2±10.5, P =0.03), global mental health (46.7±7.6 vs 43.1±9.2, P =0.01), and social isolation (52.2±7.5 vs 55.4±7.4, P =0.01). Multivariable analysis to account for the effects of other gender-affirming surgeries, hormone therapy duration, preexisting mental health diagnoses, socioeconomic disparities, and patient-reported quality of social relationships on psychosocial functioning demonstrated that completion of FFS was independently predictive of improved scores. CONCLUSIONS: Gender-affirming FFS improves the quality of life by multiple psychosocial domains in transfeminine patients.


Asunto(s)
Cirugía de Reasignación de Sexo , Personas Transgénero , Transexualidad , Masculino , Humanos , Adulto , Personas Transgénero/psicología , Feminización/cirugía , Calidad de Vida , Transexualidad/cirugía
9.
J Comput Assist Tomogr ; 47(6): 882-889, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37948362

RESUMEN

ABSTRACT: The purpose of this article is to provide a comprehensive review of the imaging findings along with histopathologic correlation of mature (benign) teratomas and malignant ovarian teratomas, which include both immature teratomas and malignant degeneration of mature teratomas. The radiologist's ability to provide an accurate diagnosis plays an essential role in guiding the interdisciplinary care of patients with malignant teratomas and improving their outcomes.


Asunto(s)
Neoplasias Ováricas , Teratoma , Femenino , Humanos , Imagen Multimodal , Teratoma/diagnóstico por imagen , Teratoma/patología , Neoplasias Ováricas/diagnóstico por imagen
10.
Postgrad Med J ; 99(1172): 624-630, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37319162

RESUMEN

Despite the shift towards consultant-led care, many patients with trauma are still seen by junior doctors. Previous research has demonstrated that junior doctors feel unprepared to work in acute care but there is a paucity of recent research in trauma specifically. Thus, a national study is required to investigate the current state of undergraduate trauma teaching and identify specific areas for improvement. Between August and September 2020, a 35-item structured questionnaire was distributed among doctors who graduated from UK medical schools within the last 4 years. The questionnaire retrospectively assessed their experience of trauma teaching at medical school and their confidence to diagnose and manage patients with trauma. 398 responses were recorded from graduates of 39 UK medical schools. With 79.6% reporting only 0-5 hours of bedside trauma teaching and 51.8% reporting less than 20 hours in Accident and Emergency, graduates reported that trauma teaching was deficient compared with other specialties (78.1%). The majority of graduates were not confident in the initial assessment (72.9%) of a patient with trauma and almost all felt that a short course in trauma would be useful (93.7%). 77.4% of students felt that online learning would be beneficial and 92.9% felt that simulation would be useful. There is lack of standardised undergraduate trauma teaching nationally; a formal undergraduate teaching to ensure that new graduates are competent in the management of trauma would be supported by students. It is likely that a blended learning approach, incorporating e-learning with traditional teaching and clinical experience would be well received.


Asunto(s)
Educación de Pregrado en Medicina , Medicina , Estudiantes de Medicina , Humanos , Estudios Retrospectivos , Estudiantes , Curriculum , Aprendizaje , Encuestas y Cuestionarios , Enseñanza
11.
J Stroke Cerebrovasc Dis ; 32(7): 107167, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37146402

RESUMEN

OBJECTIVES: Cerebral cavernous malformation (CCM) affects more than a million Americans but advanced care for symptomatic lesions and access to research studies is largely limited to referral academic centers MATERIALS AND METHODS: A cohort of CCM patients screened for research studies at an accredited center of excellence for CCM was analyzed. Demographics, lesion location, history of hemorrhage, insurance type and area of deprivation index (ADI) were collected. Primary outcomes were clinical follow-up within a year from initial evaluation, and enrollment and adherence in clinical trials among eligible subjects RESULTS: A majority (52.8%) of CCM patients evaluated had a high socioeconomic status (SES) (ADI 1-3), and only 11.5% were African American. Patients who had a symptomatic bleed were more likely to follow-up (p=0.01), and those with brainstem lesion were more likely to enroll/adhere in a clinical trial (p=0.02). Rates of clinical follow-up were similar across different ADI groups, insurance coverage and race. Patients who were uninsured/self-paying, and African Americans were more likely to decline/drop from clinical trials (OR 2.4, 95% CI 0.46-10.20 and OR 2.2, 95% CI 0.33-10.75, respectively), but differences were not statistically significant CONCLUSIONS: Access of disadvantaged patients to center of excellence care and research remains limited despite geographic proximity to their community. Patients with lower SES and African Americans are as likely to follow-up clinically, but there were trends of differences in enrollment/adherence in clinical trials. Mitigation efforts should target systemic causes of low access to specialized care among uninsured and African American patients.


Asunto(s)
Ensayos Clínicos como Asunto , Hemangioma Cavernoso del Sistema Nervioso Central , Factores Socioeconómicos , Humanos , Negro o Afroamericano , Estudios de Seguimiento , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/terapia , Hemangioma Cavernoso del Sistema Nervioso Central/patología , Hemorragia , Participación del Paciente , Selección de Paciente
12.
Cleft Palate Craniofac J ; 60(8): 949-955, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-35469458

RESUMEN

OBJECTIVE: The current study investigated the influence of the coronavirus (COVID-19) pandemic on patients with congenital craniofacial diagnoses. METHODS: Patients (n = 66) with craniofacial diagnoses aged between 8 and 17 were prospectively evaluated with longitudinal psychosocial assessments using the anger, anxiety, depressive symptoms, and peer relationships instruments within the pediatric Patient-Reported Outcomes Measurement Information System (PROMIS). The COVID-19 cohort (n = 33) included patients with assessments within 2 years prior to the pandemic (t0) and during the pandemic (t1; March 2020 to March 2021). An age-matched comparison cohort (n = 33) with similar demographics and diagnoses included patients assessed twice over 3 years prior to the pandemic. RESULTS: All PROMIS measures were in the average range clinically for both groups across time points. However, the COVID-19 group reported a significant increase in depressive symptoms during the pandemic (t1) compared to pre-pandemic (t0) scores (48.2 ± 10.1 vs 44.3 ± 9.4, P = .04, d = -0.37), while the comparison group did not demonstrate any differences in psychosocial functioning between t0 and t1. For the COVID-19 cohort, only the pandemic timeframe (r = 0.21, P = .03) was significantly associated with increased depressive symptom scores, and no other sociodemographic or medical variables were associated with depressive symptoms. CONCLUSIONS: Self-reported depressive symptoms increased during the COVID-19 pandemic in patients with congenital craniofacial diagnoses. Longitudinal studies are needed to elucidate whether such changes will be persistent or compound known variables associated with psychosocial functioning.


Asunto(s)
Ansiedad , COVID-19 , Depresión , Adolescente , Niño , Preescolar , Humanos , Ansiedad/epidemiología , COVID-19/epidemiología , COVID-19/psicología , Depresión/epidemiología , Pandemias , Autoinforme
13.
Cleft Palate Craniofac J ; : 10556656231219439, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38086751

RESUMEN

To describe the long-term treatment course of bone-anchored maxillary protraction (BAMP) and evaluate orthognathic surgical indications after BAMP.Retrospective case series.Craniofacial/Cleft Palate Program at the Orthopaedic Institute for Children in Los Angeles, CA.Twelve male patients with cleft palate (CP), unilateral cleft lip and palate (UCLP), or bilateral cleft lip and palate (BCLP) and Class III malocclusion treated with BAMP (mean age: 11.4 ± 2.6 years) were included.BAMP treatment was performed by placement of bone-anchored maxillary and mandibular plates connected with intraoral Class III dental elastics or maxillary plates connected to a facemask.We retrospectively assessed BAMP treatment variables, including age at surgery, revision surgeries, and treatment duration. The primary goal was correction to class I occlusion.Twelve patients underwent BAMP treatment for an average of 4.4 ± 2.4 years. Two patients were corrected to class I occlusion at the time of this report. Le Fort I advancement was no longer required in two patients (16.7%), it was required for nine patients (75.0%) and was completed for one patient following BAMP treatment (8.3%).This preliminary report demonstrated that BAMP treatment may be associated with a minimal reduction in the requirement for Le Fort I advancement at skeletal maturity. Future studies with larger sample sizes are necessary to confirm this association.

14.
Cleft Palate Craniofac J ; : 10556656231169483, 2023 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-37077147

RESUMEN

OBJECTIVE: To evaluate the role of psychosocial well-being on perioperative pain and opioid use among patients with cleft lip and palate (CLP) undergoing alveolar bone grafting (ABG). DESIGN: Retrospective review. SETTING: Tertiary level craniofacial clinic. PARTICIPANTS: 34 patients with CLP (median age: 11.7 years), including 25 (73.5%) unilateral CLP and 9 (26.5%) bilateral CLP, who underwent ABG from 2015 to 2022. INTERVENTIONS: ABG using iliac crest bone graft. Patients were prospectively administered four patient-reported psychosocial instruments from the Patient-Reported Outcomes Measurement Information System. MAIN OUTCOME MEASURES: Perioperative opioid use in morphine equivalent dosage/kilogram, patient-reported pain scores, and length of hospital stay after ABG. RESULTS: Patient-reported anxiety (r = 0.41, p = 0.02) and depressive symptoms (r = 0.35, p = 0.04) correlated to higher perioperative opioid usage. Multivariable regression models including psychosocial scores, total acetaminophen usage, length of surgery, and other simultaneous surgeries were developed for total opioid usage, patient-reported pain, and length of hospital stay. Patient-reported anxiety was independently predictive of higher perioperative opioid use (ß=0.36, p = 0.01) and higher pain scores (ß=0.39, p = 0.02), but not length of hospital stay. CONCLUSIONS: We identified an association for patient-reported anxiety and perioperative opioid use and pain in a CLP cohort undergoing ABG. Future considerations in preoperative patient and family consultation may be indicated in patients self-reporting higher anxiety in an effort to minimize perioperative opioid usage.

15.
J Cell Sci ; 133(5)2020 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-31964705

RESUMEN

The macrophage checkpoint receptor SIRPα signals against phagocytosis by binding CD47 expressed on all cells - including macrophages. Here, we found that inhibiting cis interactions between SIRPα and CD47 on the same macrophage increased engulfment ('eating') by approximately the same level as inhibiting trans interactions. Antibody blockade of CD47, as pursued in clinical trials against cancer, was applied separately to human-derived macrophages and to red blood cell (RBC) targets for phagocytosis, and both scenarios produced surprisingly similar increases in RBC engulfment. Blockade of both macrophages and targets resulted in hyper-phagocytosis, and knockdown of macrophage-CD47 likewise increased engulfment of 'foreign' cells and particles, decreased the baseline inhibitory signaling of SIRPα, and linearly increased binding of soluble CD47 in trans, consistent with cis-trans competition. Many cell types express both SIRPα and CD47, including mouse melanoma B16 cells, and CRISPR-mediated deletions modulate B16 phagocytosis, consistent with cis-trans competition. Additionally, soluble SIRPα binding to human CD47 displayed on Chinese hamster ovary (CHO) cells was suppressed by SIRPα co-display, and atomistic computations confirm SIRPα bends and binds CD47 in cis Safety and efficacy profiles for CD47-SIRPα blockade might therefore reflect a disruption of both cis and trans interactions.


Asunto(s)
Antígenos de Diferenciación , Antígeno CD47 , Animales , Antígeno CD47/genética , Células CHO , Cricetinae , Cricetulus , Macrófagos , Fagocitosis , Receptores Inmunológicos/genética
16.
J Craniofac Surg ; 33(2): 436-439, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34446672

RESUMEN

INTRODUCTION: Orofacial clefts are the most common craniofacial anomaly observed in the United States. Permitted by recent advancements in anesthesia and multimodal pain management, there has been a trend toward outpatient cleft lip repair to alleviate hospital burden and minimize healthcare costs. The purpose of this study was to compare complication rates between outpatient and inpatient cleft lip repair from large national samples as well as identify preoperative factors that predicted discharge status. METHODS: The National Surgical Quality Improvement Program database for pediatrics was used to analyze 30-day outcomes for all patients undergoing cleft lip repair (CPT (current procedural terminology) code 40700) from 2012 to 2019. Complication rates were compared across 3 groups: same day discharge, next day discharge, and later discharge. Preoperative factors, including comorbidities and demographics, were analyzed to determine the impact of discharge date on complications as well as identify independent predictors of discharge timing and perioperative complications. RESULTS: A total of 6689 patients underwent primary cleft lip repair, with 16.8% discharging on day of surgery, and 72.4% discharging 1 day after surgery. Complication rates were statistically equivalent between same day and next day discharge. Preoperative factors predicting complication and postoperative admission included age <6 months and weight less than ten pounds at the time of surgery. Patients discharged after more than 1 day in the hospital had higher rates of complications as well as more preoperative comorbidities. CONCLUSIONS: Complication rates between same day and next day discharge are equivalent, suggesting that same day discharge is a safe option in select patients. Clinical judgment is critical in making these decisions.


Asunto(s)
Labio Leporino , Fisura del Paladar , Niño , Labio Leporino/complicaciones , Labio Leporino/cirugía , Fisura del Paladar/cirugía , Humanos , Lactante , Alta del Paciente , Complicaciones Posoperatorias/epidemiología , Mejoramiento de la Calidad , Estudios Retrospectivos , Estados Unidos
17.
Aesthet Surg J ; 42(1): NP38-NP40, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34137855

RESUMEN

BACKGROUND: The proliferation of social media in plastic surgery poses significant difficulties for the public in determining legitimacy of information. This work proposes a system based on social network analysis (SNA) to assess the legitimacy of information contributors within a plastic surgery community. OBJECTIVES: The aim of this study was to quantify the centrality of individual or group accounts on plastic surgery social media by means of a model based on academic plastic surgery and a single social media outlet. METHODS: To develop the model, a high-fidelity, active, and legitimate source account in academic plastic surgery (@psrc1955, Plastic Surgery Research Council) appearing only on Instagram (Facebook, Menlo Park, CA) was chosen. All follower-followed relationships were then recorded, and Gephi (https://gephi.org/) was used to compute 5 different centrality metrics for each contributor within the network. RESULTS: In total, 64,737 unique users and 116,439 unique follower-followed relationships were identified within the academic plastic surgery community. Among the metrics assessed, the in-degree centrality metric is the gold standard for SNA, hence this metric was designated as the centrality factor. Stratification of 1000 accounts by centrality factor demonstrated that all of the top 40 accounts were affiliated with a plastic surgery residency program, a board-certified academic plastic surgeon, a professional society, or a peer-reviewed journal. None of the accounts in the top decile belonged to a non-plastic surgeon or non-physician; however, this increased significantly beyond the 50th percentile. CONCLUSIONS: A data-driven approach was able to identify and successfully vet a core group of interconnected accounts within a single plastic surgery subcommunity for the purposes of determining legitimate sources of information.


Asunto(s)
Procedimientos de Cirugía Plástica , Medios de Comunicación Sociales , Cirujanos , Cirugía Plástica , Macrodatos , Humanos
18.
Ann Plast Surg ; 86(2): 226-232, 2021 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33449467

RESUMEN

BACKGROUND: Craniosynostosis is among the abnormalities that are more commonly encountered by craniofacial surgeons. Although the overall concepts for cranial vault remodeling are relatively simple, osteotomy designs and methods for calvarial rearrangement are highly varied. In this work, we present a summary of the known designs for correction of single-suture craniosynostosis. METHODS: A review of the literature was performed of the more frequently used osteotomy designs for single-suture craniosynostosis, as well as their reported results and outcomes. Also reviewed are some of the current available approaches for the diagnosis and surgical planning for single-suture craniosynostosis. RESULTS: There remains a diversity of techniques available for the reconstruction of each fused cranial suture. Certain osteotomy designs are reported in the literature and are used by craniofacial surgeons more frequently. Each has its own benefits and disadvantages, and there is a growing body of outcome data available to guide surgical decision-making. Regarding diagnosis and surgical planning, computed tomography with 3-dimensional reconstruction remains the diagnostic standard of care, and efforts are ongoing to develop and implement new diagnostic modalities like Black Bone MRI to reduce radiation exposure. CONCLUSIONS: There has been ongoing evolution of the surgical techniques available to reconstruct single-suture craniosynostosis, leading to ever-improving patient outcomes.


Asunto(s)
Craneosinostosis , Procedimientos de Cirugía Plástica , Suturas Craneales , Craneosinostosis/diagnóstico por imagen , Craneosinostosis/cirugía , Humanos , Lactante , Osteotomía , Cráneo/cirugía , Suturas
19.
Ann Plast Surg ; 87(5): 589-599, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34699435

RESUMEN

BACKGROUND: Facial deformities in syndromic craniosynostosis are not only functionally, psychosocially, and aesthetically impairing but also notoriously challenging to reconstruct. Whether facial suture synostosis plays a significant role in the pathogenesis of these deformities is inadequately studied in human patients. METHODS: The MEDLINE database was queried using a methodologically generated search term inventory. Article inclusion was adjudicated by 2 authors after independent review. Articles provided insight into facial suture involvement in either syndromic craniosynostosis patients or animal models of disease. RESULTS: Comprehensive review yielded 19 relevant articles meeting inclusion criteria. Mid-20th century craniofacial biologists characterized how patent facial sutures are essential for normal postnatal facial development. They also posited that premature ossification disrupts growth vectors, causing significant dysmorphologies. Recently, facial suture synostosis was found to cause midfacial deformities independent of cranial base pathology in mouse models of syndromic craniosynostosis. Few recent studies have begun exploring facial suture involvement in patients, and although they have paved the way for future research, they bear significant limitations. CONCLUSIONS: The hypothesis that facial suture synostosis acts in conjunction with cranial base pathology to produce the prominent, multifocal facial deformities in syndromic craniosynostosis may fundamentally alter surgical management and warrants further investigation. Methodically evaluating the literature, this review synthesizes all basic science and human clinical research thus far on the role of facial sutures in syndromic craniosynostosis and elucidates important topics for future research. We ultimately identify the need for rigorous imaging studies that longitudinally evaluate facial osteology across patients with various craniosynostosis syndromes.


Asunto(s)
Suturas Craneales , Craneosinostosis , Animales , Suturas Craneales/cirugía , Craneosinostosis/cirugía , Humanos , Ratones , Suturas , Síndrome , Tomografía Computarizada por Rayos X
20.
Ann Plast Surg ; 86(1): 109-114, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32079810

RESUMEN

Individuals with gender dysphoria often seek medical interventions, such as hormone treatment and surgery, to live as their identified gender. Cross-sex hormone therapy typically consists of various estrogen formulations which confer varying risks of venous thromboembolism (VTE). Currently, there is no standard practice by surgeons regarding the preoperative gender-affirming surgery (GAS) hormone regimen of male-to-female (MTF) patients to minimize thromboembolic postoperative complications. The aim of this review is to examine the current literature on VTE occurring in MTF transgender patients on cross-sex hormone therapy (CSHT) when undergoing various gender-affirming surgeries-facial feminization surgery (FFS), top surgery (TS), and bottom surgery (BS)-to understand how evidence-based recommendations regarding perioperative hormone regimens can be established to improve clinical outcomes. Within the past 25 years, 7 published studies have examined the incidence of VTE in MTF patients undergoing GAS procedures. Two of these articles examined MTF patients undergoing FFS, 1 article reported a patient who had undergone BS and FFS during the same hospitalization, and the remaining 4 articles investigated VTE risk in BS. Our review supports that plastic surgeons who perform GAS are divided on their preferred CSHT protocols, with some requiring patients to suspend their CSHT weeks before surgery and others allowing patients to continue CSHT through the day of surgery. Three of the 7 studies detailed a CSHT perioperative regimen which instructed patients to suspend CSHT sometime before surgery; 1 study tapered CSHT to lower levels before surgery; the remaining 3 studies did not specify a CSHT perioperative regimen. This review highlights the paucity of data failing to support that continuing CSHT through GAS elevates VTE risk. We conclude that in the absence of definitive VTE risk factors (e.g., smoking, clotting disorders, or malignancy), surgeons may engage MTF patients in joint decision-making process to determine the most optimal perioperative CSHT management plan on a case-by-case basis. Future studies are warranted to evaluate VTE risk based on patient age, type of surgery, operating time, prophylactic measures, follow-up time, and CSHT perioperative regimens.


Asunto(s)
Disforia de Género , Personas Transgénero , Transexualidad , Tromboembolia Venosa , Femenino , Disforia de Género/cirugía , Hormonas Esteroides Gonadales , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Factores de Riesgo , Transexualidad/cirugía , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
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